Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a high risk of postoperative acute kidney injury (AKI). Due to limitations of current diagnostic strategies, we sought to determine whether free hemoglobin (fHb) ratio (ie, levels of fHb at the end of CPB divided by baseline fHb) could predict AKI after on-pump cardiac surgery. METHODS: This is a secondary analysis of a randomized controlled trial comparing the effect of nitric oxide (intervention) versus nitrogen (control) on AKI after cardiac surgery (NCT01802619). A total of 110 adult patients in the control arm were included. First, we determined whether fHb ratio was associated with AKI via multivariable analysis. Second, we verified whether fHb ratio could predict AKI and incorporation of fHb ratio could improve predictive performance at an early stage, compared with prediction using urinary biomarkers alone. We conducted restricted cubic spline in logistic regression for model development. We determined the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and calibration (calibration plot and accuracy, ie, number of correct predictions divided by total number of predictions). We also used AUC test, likelihood ratio test, and net reclassification index (NRI) to compare the predictive performance between competing models (ie, fHb ratio versus neutrophil gelatinase-associated lipocalin [NGAL], N-acetyl-ß-d-glucosaminidase [NAG], and kidney injury molecule-1 [KIM-1], respectively, and incorporation of fHb ratio with NGAL, NAG, and KIM-1 versus urinary biomarkers alone), if applicable. RESULTS: Data stratified by median fHb ratio showed that subjects with an fHb ratio >2.23 presented higher incidence of AKI (80.0% vs 49.1%; P = .001), more need of renal replacement therapy (10.9% vs 0%; P = .036), and higher in-hospital mortality (10.9% vs 0%; P = .036) than subjects with an fHb ratio ≤2.23. fHb ratio was associated with AKI after adjustment for preestablished factors. fHb ratio outperformed urinary biomarkers with the highest AUC of 0.704 (95% confidence interval [CI], 0.592-0.804) and accuracy of 0.714 (95% CI, 0.579-0.804). Incorporation of fHb ratio achieved better discrimination (AUC test, P = .012), calibration (likelihood ratio test, P < .001; accuracy, 0.740 [95% CI, 0.617-0.832] vs 0.632 [95% CI, 0.477-0.748]), and significant prediction increment (NRI, 0.638; 95% CI, 0.269-1.008; P < .001) at an early stage, compared with prediction using urinary biomarkers alone. CONCLUSIONS: Results from this exploratory, hypothesis-generating retrospective, observational study shows that fHb ratio at the end of CPB might be used as a novel, widely applicable biomarker for AKI. The use of fHb ratio might help for an early detection of AKI, compared with prediction based only on urinary biomarkers.

Retrograde Autologous Priming in Cardiac Surgery: Results From a Systematic Review and Meta-analysis.

BACKGROUND: Retrograde autologous priming (RAP) before cardiopulmonary bypass (CPB) may minimize allogeneic red cell transfusion. We conducted a systematic review of the literature to examine the impact of RAP on perioperative allogeneic red cell transfusions in cardiac surgical patients. METHODS: This study involved a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating the use of RAP in cardiac surgery involving CPB. The primary outcome was intraoperative allogeneic red cell transfusion. Secondary outcomes included whole hospital allogeneic transfusions and adverse events such as acute kidney injury (AKI) and stroke. RESULTS: A total of 11 RCTs (n = 1337 patients) were included, comparing RAP patients (n = 674) to control (n = 663). In addition, 10 observational studies (n = 2327) were included, comparing RAP patients (n = 1257) to control (n = 1070). Overall, RAP was associated with a significantly reduced incidence of intraoperative red cell transfusion (n = 18 studies; odds ratio [OR] = 0.34; 95% confidence interval [CI], 0.22-0.55, P < .001) compared to controls. This effect was seen among RCTs (n = 10 studies; OR = 0.19; 95% CI, 0.08-0.45, P < .001) and observational studies (n = 8 studies; OR = 0.66; 95% CI, 0.50-0.87, P = .004) in isolation. RAP was also associated with a significantly reduced incidence of whole hospital red cell transfusion (n = 5 studies; OR = 0.28; 95% CI, 0.19-0.41, P < .001). Among the studies that reported AKI and stroke outcomes, there was no statistically significant increased odds of AKI or stroke in either RAP or control patients. CONCLUSIONS: Based on the pooled results of the available literature, RAP is associated with a significant reduction in intraoperative and whole hospital allogeneic red cell transfusion. Use of RAP may prevent hemodilution of cardiac surgical patients and thus, lessen transfusions. Additional high-quality prospective studies are necessary to determine the ideal priming volume necessary to confer the greatest benefit without incurring organ injury.

Interleukin -17 Serum Levels and Polymorphisms in Acute Kidney Injury Patients.

BACKGROUND: Cardiopulmonary bypass (CPB) has been demonstrated to provoke a systemic inflammatory response believed to be responsible for some of the serious postoperative complications such as renal dysfunction. Therefore, we tested the hypothesis suggesting that the serum levels of IL- 17A (IL-17), as an inflammatory cytokine, and its gene variants are associated with acute kidney injury after CPB (AKI-CPB). METHODS: A total of 135 Iranian patients undergoing cardiopulmonary bypass were included in this study, of whom 65 (48.1%) developed AKI. Blood specimens were collected preoperatively and at 12 hours postoperatively. The IL-17 gene polymorphisms (rs2275913 and rs3819024) were determined using sequence-specific primers (PCR-SSP) technique.Pre- and postoperative IL-17 levels were measured and analyzed in relation to polymorphisms. RESULTS: IL-17 concentrations in CBP subjects, were increased after cardiopulmonary bypass (P<0.00001)but there were no statistically significant differences in IL-17 serum level between AKI and non-AKI groups. Different genotypes of IL-17 rs2275913 SNP (G→A) were associated with different circulating IL-17 levels before bypass and also after AKI development. There were no associations between gene polymorphisms (rs2275913and rs3819024) and incidence of AKI- CPB. There was an association between thers2275913 SNP and the severity of AKI. CONCLUSION: This study clarified that the rs2275913 SNP to some extent determines plasma IL-17 concentrations in CPB patients. No significant association was found between IL-17 levels or gene polymorphisms (rs2275913and rs3819024) and incidence of AKI-CPB. Our results suggest that there is an association between rs2275913 and the severity of AKI- CPB.

The Future of Open Heart Surgery in the Era of Robotic and Minimal Surgical Interventions.

It has been over two decades since the very first robotic cardiac surgery was performed. Over the years, there has been an increase in the demand for less invasive cardiac surgical techniques. Developments in technology and engineering have provided an opportunity for robotic surgery to be applied to a variety of cardiac procedures, including coronary revascularisation, mitral valve surgery, atrial fibrillation ablation, and others. In coronary revascularisation, it is becoming more widely used in single vessel, as well as hybrid coronary artery approaches. Currently, several international centres are specialising in a totally endoscopic coronary artery bypass surgery involving multiple vessels. Mitral valve and other intracardiac pathologies such as atrial septal defect and intracardiac tumour are also increasingly being addressed robotically. Even though some studies have shown good results with robot-assisted cardiac surgery, there are still concerns about safety, cost and clinical efficacy. There are also limitations and additional challenges with the management of cardiopulmonary bypass and myocardial protection during robotic surgery. Implementing novel strategies to manage these challenges, together with careful patient selection can go a long way to producing satisfactory results. This review examines the current evidence behind robotic surgery in various aspects of cardiac surgery.

Effect of ultrafiltration on extravascular lung water assessed by lung ultrasound in children undergoing cardiac surgery: a randomized prospective study.

BACKGROUND: Increased lung water and the resultant atelectasis are significant pulmonary complications after cardiopulmonary bypass (CPB) in children undergoing cardiac surgery; these complications are observed after CPB than after anaesthesia alone. Ultrafiltration has been shown to decrease total body water and postoperative blood loss and improve the alveolar to arterial oxygen gradient and pulmonary compliance. This study investigated whether conventional ultrafiltration during CPB in paediatric heart surgeries influences post-bypass extravascular lung water (EVLW) assessed by lung ultrasound (LUS). METHODS: This randomized controlled study included 60 patients with congenital heart disease (ASA II-III), aged 1 to 48 months, with a body weight > 3 kg. Conventional ultrafiltration targeting a haematocrit (HCT) level of 28% was performed on the ultrafiltration group, while the control group did not receive ultrafiltration. LUS scores were recorded at baseline and at the end of surgery. The PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen), urine output, and haemodynamic parameters were also recorded. RESULTS: LUS scores were comparable between the two groups both at baseline (p = 0.92) and at the end of surgery (p = 0.95); however, within the same group, the scores at the end of surgery significantly differed from their baseline values in both the ultrafiltration (p = 0.01) and non-ultrafiltration groups (p = 0.02). The baseline PaO2/FiO2 ratio was comparable between both groups. at the end of surgery, The PaO2/FiO2 ratio increased in the ultrafiltration group compared to that in the non-ultrafiltration group, albeit insignificant (p = 0.16). no correlation between the PaO2/FiO2 ratio and LUS score was found at baseline (r = - 0.21, p = 0.31). On the other hand, post-surgical measurements were negatively correlated (r = - 0.41, p = 0.045). CONCLUSION: Conventional ultrafiltration did not alter the EVLW when assessed by LUS and oxygenation state. Similarly, ultrafiltration did not affect the urea and creatinine levels, intensive care unit (ICU) stays, ventilation days, or mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03146143 registered on 29-April-2017.

What's New in Cardiopulmonary Bypass.

This is a narrative review of recent articles (mainly published in 2017 and 2018) related to the conduct of cardiopulmonary bypass (CPB) that should be of interest to the cardiac anesthesiologist. Some of the topics covered include recent guidelines on temperature management, anticoagulation, perfusion practice, use of transesophageal echocardiography during CPB, optimal mean arterial pressure, vasoplegia, bleeding, perioperative anemia, post-cardiac surgery transfusion, acute kidney injury, delirium and cognitive decline, CPB during pregnancy, lung management, radial-to-femoral artery pressure gradients during CPB, prophylactic perioperative intra-aortic balloon pump, del Nido cardioplegia, antibiotic prophylaxis, and use of levosimendan in cardiac surgery. The review concludes with a perspective on the effect of these development on the practice of cardiac anesthesia.

Toward Understanding Cerebral Blood Flow during Cardiopulmonary Bypass: Implications for the Central Nervous System.

Factors and Their Influence on Regional Cerebral Blood Flow during Nonpulsatile Cardiopulmonary Bypass. By Govier AV, Reves JG, McKay RD, Karp RB, Zorn GL, Morawetz RB, Smith LR, Adams M, and Freeman AM. Ann Thorac Surg. 1984; 38:609-13. Reprinted with permission.In this study, we examined the relationship of regional cerebral blood flow (CBF) to mean arterial pressure, systemic blood flow, partial pressure of arterial carbon dioxide (PaCO2), nasopharyngeal temperature, and hemoglobin during hypothermic nonpulsatile cardiopulmonary bypass (CPB). Regional CBF was determined by clearance of xenon 133 in 67 patients undergoing coronary bypass grafting procedures. There was a significant decrease in regional CBF (55% decrease) during CPB, with nasopharyngeal temperature and PaCO2 being the only two significant factors (p < 0.05). In a subgroup of 10 patients, variation of pump flow between 1.0 and 2.0 L/min/m2 did not significantly affect regional CBF. We conclude that cerebral autoregulation is retained during hypothermic CPB. Under the usual conditions of CPB, variations in flow and pressure are not associated with important physiologic or detrimental clinical effects.

Trends and Updates on Cardiopulmonary Bypass Setup in Pediatric Cardiac Surgery.

Perfusion strategies for cardiopulmonary bypass have direct consequences on pediatric cardiac surgery outcomes. However, inconsistent study results and a lack of uniform evidence-based guidelines for pediatric cardiopulmonary bypass management have led to considerable variability in perfusion practices among, and even within, institutions. Important aspects of cardiopulmonary bypass that can be optimized to improve clinical outcomes of pediatric patients undergoing cardiac surgery include extracorporeal circuit components, priming solutions, and additives. This review summarizes the current literature on circuit components and priming solution composition with an emphasis on crystalloid, colloid, and blood-based primes, as well as mannitol, bicarbonate, and calcium.

A Propensity-Score Matched Analysis on Outcomes Using Recombinant Activated Factor VII in Pediatric Cardiac Surgery.

OBJECTIVE: To evaluate the effect of recombinant activated factor VII (rFVIIa) administration on outcomes in pediatric cardiac surgery patients with postoperative bleeding. DESIGN: A propensity score-matched retrospective study. SETTING: Single tertiary medical center. PARTICIPANTS: The study comprised 151 patients who received treatment with rFVIIa and were matched with control patients at a 1:2 ratio. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were thrombotic events, renal replacement therapy (RRT), and mortality. The secondary endpoints were length of intensive care unit stay and the reexploration rate. Patients in the rFVIIa group showed no significant differences in thrombotic events (odds ratio [OR] 1.03; 95% confidence interval [CI] 0.48-2.21; p = 0.948), mortality (OR 0.94; 95% CI 0.42-2.13; p = 0.891), and RRT (OR 1.38; 95% CI 0.73-2.58; p = 0.319). However, patients in the rFVIIa group experienced a prolonged length of intensive care unit stay (5.65 [3.00-12.28] d v 3.91 [1.83-6.77] d) and an increased reexploration rate (8.2% v 3.1%). High-dose rFVIIa was an independent risk factor of thrombotic events (OR 5.17; 95% CI 1.19-22.49; p = 0.029). CONCLUSION: This study found that rFVIIa is not associated with increased risks of postoperative thrombotic events, mortality, or RRT in pediatric patients undergoing cardiac surgery. Nevertheless, rFVIIa was associated with longer intensive care unit stay and increased reexploration rate. Furthermore, the risk for thrombotic events may increase with high-dose rFVIIa.

Recent achievements and future developments in neonatal cardiopulmonary bypass.

A primary goal of improving neonatal cardiopulmonary bypass has been making the circuit smaller and reduce the blood contacting surfaces. As bypass circuit size has decreased, bloodless surgery has become possible even in neonates. Since transfusion guidelines are difficult to construct based on existing literature, these technical advances should be taken advantage of in conjunction with an individualized transfusion scheme, based on monitoring of oxygen availability to the tissues. For the majority of neonatal heart operations, several centers have shifted toward normothermic bypass even for complex neonatal surgeries, in order to avoid the adverse effects of hypothermia. Deep hypothermic circulatory arrest is no longer a necessity but an option, and selective antegrade cerebral perfusion has become common practice; however, technical uncertainties with regard to this technique have to be addressed, based on reliable neurologic monitoring. Maintenance of patient-specific heparin concentrations during bypass is another key goal, since neonates have lower baseline antithrombin concentrations and, therefore, a higher risk for inadequate thrombin inhibition and postoperative bleeding. Due to the immaturity of their hemostatic system, the standard coagulation tests alone are inappropriate to guide hemostatic therapy in neonates. The use of indirect heparin concentration assays and global viscoelastic assays in the operating room is likely to represent the optimal strategy, and requires validation in neonates. Monitoring of global and regional indexes of oxygen availability and consumption on bypass have become possible; however, their use in neonates still has outstanding technical issues which should be addressed and hence needs further validation. Due to the immaturity of the neonatal myocardium, single-shot cold cardioplegia solutions are thought to confer the best myocardial protection; their superiority when compared to more conventional modalities, however, remains to be demonstrated.

Acute Right Ventricular Failure in Cardiac Surgery During Cardiopulmonary Bypass Separation: A Retrospective Case Series of 12 Years' Experience With Intratracheal Milrinone Administration.

OBJECTIVE: To report the authors' 12 years of experience with intratracheal milrinone administration and to assess the efficacy and limitations of intratracheal milrinone bolus administration for the treatment of unexpected acute right ventricular (RV) failure in patients undergoing cardiac surgery. DESIGN: Retrospective analysis. SETTING: Single-center university hospital. PARTICIPANTS: One hundred seventy-six patients (4.6%) undergoing on-pump cardiac surgery. INTERVENTIONS: Endotracheal tube administration of milrinone (5-mg bolus) after unexpected acute RV failure during separation from cardiopulmonary bypass (CPB) weaning. RV failure was defined as the simultaneous presence of all of the following criteria: (1) hemodynamic instability or difficult separation from CPB with associated elevated central venous pressure or abnormal RV pressure waveform, (2) >20% reduction of RV fractional area change from baseline evaluated by transesophageal echocardiography, and (3) anatomical visualization of impaired or absent RV wall motion by direct intraoperative visual inspection. MEASUREMENTS AND MAIN RESULTS: Intratracheal milrinone administration was found to improve RV failure in 109 patients (61.9%) whereas RV failure persisted in 67 patients (38.1%). Using a multiple logistic regression model, severely decreased left ventricular ejection fraction (<35% v >50%) (adjusted odds ratio [OR] 3.72; 95% confidence interval [CI] 1.2-11.3; p = 0.012), longer CPB time (adjusted OR 1.014; CI 1.01-1.02; p = 0.001) and elevated postoperative fluid balance (adjusted OR 1.39; CI 1.1-1.8; p = 0.02) were found to be significant predictors of persistent RV failure. CONCLUSION: Intratracheal instillation of milrinone was associated with clinical improvement of RV failure occurring during separation from CPB in almost two-thirds of patients. Factors limiting its therapeutic efficacy include severe left ventricular dysfunction, increased fluid balance, and long CPB time.

Electroencephalogram dynamics during general anesthesia predict the later incidence and duration of burst-suppression during cardiopulmonary bypass.

OBJECTIVE: Electroencephalogram burst-suppression during general anesthesia is associated with post-operative delirium (POD). Whether burst-suppression causes POD or merely reflects susceptibility to POD is unclear. We hypothesized decreased intraoperative alpha (8-12 Hz) and beta (13-33 Hz) power prior to the occurrence of burst-suppression in susceptible patients. METHODS: We analyzed intraoperative electroencephalogram data of cardiac surgical patients undergoing cardiopulmonary bypass (CPB). We detected the incidence and duration of CPB burst-suppression with an automated burst-suppression detection algorithm. We analyzed EEG data with multitaper spectral estimation methods. We assessed associations between patient characteristics and burst-suppression using Binomial and Zero-inflated Poisson Regression Models. RESULTS: We found significantly decreased alpha and beta power (7.8-22.95 Hz) in the CPB burst-suppression cohort. The odds ratio for the association between point estimates for alpha and beta power (7.8-22.95 Hz) and the incidence of burst-suppression was 0.88 (95% CI: 0.79-0.98). The incidence rate ratio for the association between point estimates for power between the alpha and beta range and the duration of burst-suppression was 0.89 (95% CI: 0.84-0.93). CONCLUSION: Decreased intra-operative power within the alpha and beta range was associated with susceptibility to burst-suppression during CPB. SIGNIFICANCE: This dynamic may be used to develop principled neurophysiological-based approaches to aid the preemptive identification and targeted care of POD vulnerable patients.

Cognitive Decline after Delirium in Patients Undergoing Cardiac Surgery.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Cardiac surgery is associated with cognitive decline and postoperative delirium. The relationship between postoperative delirium and cognitive decline after cardiac surgery is unclear WHAT THIS ARTICLE TELLS US THAT IS NEW: The development of postoperative delirium is associated with a greater degree of cognitive decline 1 month after cardiac surgery. The development of postoperative delirium is not a predictor of cognitive decline 1 yr after cardiac surgery. BACKGROUND: Delirium is common after cardiac surgery and has been associated with morbidity, mortality, and cognitive decline. However, there are conflicting reports on the magnitude, trajectory, and domains of cognitive change that might be affected. The authors hypothesized that patients with delirium would experience greater cognitive decline at 1 month and 1 yr after cardiac surgery compared to those without delirium. METHODS: Patients who underwent coronary artery bypass and/or valve surgery with cardiopulmonary bypass were eligible for this cohort study. Delirium was assessed with the Confusion Assessment Method. A neuropsychologic battery was administered before surgery, at 1 month, and at 1 yr later. Linear regression was used to examine the association between delirium and change in composite cognitive Z score from baseline to 1 month (primary outcome). Secondary outcomes were domain-specific changes at 1 month and composite and domain-specific changes at 1 yr. RESULTS: The incidence of delirium in 142 patients was 53.5%. Patients with delirium had greater decline in composite cognitive Z score at 1 month (greater decline by -0.29; 95% CI, -0.54 to -0.05; P = 0.020) and in the domains of visuoconstruction and processing speed. From baseline to 1 yr, there was no difference between delirious and nondelirious patients with respect to change in composite cognitive Z score, although greater decline in processing speed persisted among the delirious patients. CONCLUSIONS: Patients who developed delirium had greater decline in a composite measure of cognition and in visuoconstruction and processing speed domains at 1 month. The differences in cognitive change by delirium were not significant at 1 yr, with the exception of processing speed.

Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: A randomised controlled clinical trial.

BACKGROUND: Raised plasma levels of endogenous adenosine after cardiac surgery using cardiopulmonary bypass (CPB) have been related to the incidence of postoperative atrial fibrillation (POAF). OBJECTIVE: We wished to assess if caffeine, an adenosine receptor antagonist could have a beneficial effect on the incidence of POAF. DESIGN: A randomised controlled study. SETTING: Single University Hospital. PATIENTS: One hundred and ten patients scheduled for heart valve surgery with CPB. INTERVENTIONS: We randomly assigned patients to receive peri-operative oral caffeine (400 mg every 8 h for 2 days) or placebo. Adenosine plasma concentrations and caffeine pharmacokinetic profile were evaluated in a subgroup of 50 patients. MAIN OUTCOME MEASURES: The primary endpoint was the rate of atrial fibrillation during postoperative hospital stay. RESULTS: The current study was stopped for futility by the data monitoring board after an interim analysis. The incidence of atrial fibrillation was similar in the caffeine and in the placebo group during hospital stay (33 vs. 29%, P = 0.67) and the first 3 postoperative days (18 vs. 15%; P = 0.60). Basal and postoperative adenosine plasma levels were significantly associated with the primary outcome. Adenosine plasma levels were similar in the two treatment groups. Caffeine administration was associated with a higher incidence of postoperative nausea and vomiting (27 vs. 7%, P = 0.005). CONCLUSION: Oral caffeine does not prevent POAF after heart valve surgery with CPB but increased the incidence of postoperative nausea and vomiting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, no.: NCT01999829.

Association Between Optic Nerve Head Blood Flow Measured Using Laser Speckle Flowgraphy and Radial Arterial Pressure During Aortic Arch Surgery.

OBJECTIVE: This study was designed to investigate the association between ocular blood flow measured using laser speckle flowgraphy (LSFG) and radial arterial pressure during aortic arch surgery. DESIGN: A prospective study. SETTING: A single university hospital. PARTICIPANTS: This study included 24 patients undergoing aortic arch surgery with cardiopulmonary bypass (CPB) using antegrade selective cerebral perfusion (SCP). INTERVENTIONS: Measurement of optic nerve head blood flow using LSFG and radial arterial pressure via a catheter in the radial artery METHODS AND MAIN RESULTS: Antegrade SCP was managed with 24℃ and 40-to-60 mmHg at the right radial artery, which usually corresponds to a flow rate of 10 mL/kg/min. Optic nerve head blood flow using LSFG and radial arterial blood pressure were evaluated simultaneously at the right side and recorded at the following 4 points: after the induction of anesthesia (phase 1), after the beginning of CPB (phase 2), after the beginning of antegrade SCP (phase 3), and after cessation of CPB (phase 4). A moderate positive correlation between %change of mean blur rate in the optic nerve head measured using LSFG and %change of radial mean arterial pressure was identified (r = 0.604, p < 0.001). Bland-Altman analysis showed that the bias (mean difference) was -1.2% (95% limits of agreement -47.4% to 45.0%), indicating good agreement between %changes of the values recorded using the 2 measurements. CONCLUSIONS: Intraoperative monitoring of optic nerve head blood flow using LSFG can be used as an additional cerebral perfusion parameter during aortic arch surgery with CPB using antegrade SCP.