Benchmark of Intraoperative Activity in Cardiac Surgery: A Comparison between Pre- and Post-Operative Prognostic Models.

OBJECTIVES: Despite its large diffusion and improvements in safety, the risks of complications after cardiac surgery remain high. Published predictive perioperative scores (EUROSCORE, STS, ACEF) assess risk on preoperative data only, not accounting for the intraopertive period. We propose a double-fold model, including data collected before surgery and data collected at the end of surgery, to evaluate patient risk evolution over time and assess the direct contribution of surgery. METHODS: A total of 15,882 cardiac surgery patients from a Margherita-Prosafe cohort study were included in the analysis. Probability of death was estimated using two logistic regression models (preoperative data only vs. post-operative data, also including information at discharge from the operatory theatre), testing calibration and discrimination of each model. RESULTS: Pre-operative and post-operative models were built and demonstrate good discrimination and calibration with AUC = 0.81 and 0.87, respectively. Relative difference in pre- and post-operative mortality in separate centers ranged from -0.36 (95% CI: -0.44--0.28) to 0.58 (95% CI: 0.46-0.71). The usefulness of this two-fold preoperative model to benchmark medical care in single hospital is exemplified in four cases. CONCLUSIONS: Predicted post-operative mortality differs from predicted pre-operative mortality, and the distance between the two models represent the impact of surgery on patient outcomes. A double-fold model can assess the impact of the intra-operative team and the evolution of patient risk over time, and benchmark different hospitals on patients subgroups to promote an improvement in medical care in each center.

Case-mix affects calibration of cardiosurgical severity scores.

BACKGROUND: Prognostic models are often used to assess the quality of healthcare. Several scores were developed to predict mortality after cardiac surgery, but none has reached optimal performance in subsequent validations. We validate the most used scores (EUROSCORE I and II, STS, and ACEF) on a cohort of cardiac-surgery patients, assessing their robustness against case-mix changes. METHODS: The scores were validated on 14,559 patients admitted to 16 Italian cardiosurgical ICUs participating to Margherita-Prosafe project in 2014 and 2015. Calibration was assessed through Hosmer-Lemeshow Test, standardized mortality ratio, and GiViTI calibration test and belt. Discrimination was measured by the area under the ROC curve. RESULTS: The study included 10,317 patients who were eligible to the calculation of the STS Score (4156 isolated valve, 4681 isolated CABG and 1480 single valve and CABG) which calibrated well in these subgroups. The ACEF Score and EUROSCORE I and II were available for 14,139, and 14,071 patients, respectively. EUROSCORE I significantly overestimated mortality; EUROSCORE II calibrated well overall, but underestimated mortality of patients undergoing complex surgery and non-elective ones. The ACEF Score calibrated poorly in elective and non-elective patients. Discrimination was acceptable for all models (AUC>0.70), but not for the ACEF Score. CONCLUSIONS: Cardiac surgery scores calibrate poorly when the case-mix of validation and development samples differs. To grant reliability for benchmarking, they should be validated in the clinical settings on which they are applied and updated periodically. Advanced statistical tools are essential for the correct interpretation and application of severity scores.

Differential modulatory effects of Propofol and Sevoflurane anesthesia on blood monocyte HLA-DR and CD163 expression during and after cardiac surgery with cardiopulmonary bypass: a preliminary randomized flow cytometry study.

INTRODUCTION: The increase of the anti-inflammatory CD163highHLA-DRlow blood monocyte subset is one of the mechanisms dampening inflammation during cardiac surgery with cardiopulmonary bypass. We evaluated the effect of two different anesthetic protocols, intravenous Propofol infusion or Sevoflurane-gas administration, on the perioperative frequency of this subset. METHODS: Blood from patients (Propofol = 11, Sevoflurane = 13) undergoing minimally invasive mitral valve surgery was drawn preoperatively (T1), before declamping (T2), at 6 (T3), 24 (T4), 48 (T5), and 72 hours (T6) after declamping. C-reactive protein, haptoglobin, and lactate dehydrogenase were measured. A hemolytic index, as C-reactive protein/haptoglobin ratio, was introduced. Monocyte expression of HLA-DR, CD163, and the CD163highHLA-DRlow subset fraction was quantified by flow cytometry. Baseline-referred variations of plasmatic and cellular data at T2 were normalized for clamping times. Subsequent time-point variations were normalized for the final cardiopulmonary bypass times. RESULTS: Variations of hemolytic index and lactate dehydrogenase were higher with Propofol at T3 (p = 0.004 and p = 0.02, respectively) when compared with Sevoflurane. At T2, the down-modulation of CD163 was higher with Propofol (p = 0.005). Starting from T3, the up-regulatory trend of CD163 was basically higher with Propofol, although not significantly. Propofol induced higher increments of HLA-DR low fractions, at T2 (p = 0.04) and, to a lesser extent, at T4 (p = 0.06). Starting from T3, the CD163highHLA-DRlow subset variations were higher with Propofol, especially at T4 and T6. CONCLUSION: Propofol seems to induce a higher postoperative fraction of the CD163highHLA-DRlow monocyte subset. This could represent either a compensatory mechanism dampening the higher inflammatory condition observed with Propofol at T2 or a consequence of a higher postoperative Propofol-induced hemolysis.

Mortality in Multicenter Critical Care Trials: An Analysis of Interventions With a Significant Effect.

OBJECTIVES: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. DATA SOURCES: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. STUDY SELECTION: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. DATA EXTRACTION: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. DATA SYNTHESIS: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. CONCLUSIONS: We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.

Myocardial conditioning techniques in off-pump coronary artery bypass grafting.

Off-pump coronary artery bypass surgery by avoiding cardioplegic arrest seems to reduce the risk of ischemic myocardial injury. However, even short-term regional ischemic periods, hemodynamic instability and arrhythmias associated with the procedure can be responsible for myocardial damage. Conditioning, a potential cardio-protective tool during on-pump cardiac surgery, has hardly been investigated in the context of off-pump surgery. There are virtually no large trials on remote ischemic preconditioning and the majority of reports have focused on central ischemic conditioning. Similarly, volatile anesthetic agents with conditioning effect like ischemic preconditioning have been shown to reduce cardiac injury during on-pump procedures but have not been validated in the off-pump scenario. Here, we review the available evidence on myocardial conditioning, either with ischemia/reperfusion or volatile anesthetic agents in patients undergoing off-pump coronary artery surgery.

Reducing mortality in acute kidney injury patients: systematic review and international web-based survey.

OBJECTIVE: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting. DESIGN AND SETTING: Systematic literature review and international web-based survey. PARTICIPANTS: More than 300 physicians from 62 countries. INTERVENTIONS: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality. MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions. CONCLUSION: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics.

Randomized evidence for reduction of perioperative mortality.

OBJECTIVE: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. DESIGN AND SETTING: A web-based international consensus conference. PARTICIPANTS: More than 1,000 physicians from 77 countries participated in this web-based consensus conference. INTERVENTIONS: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. MEASUREMENTS AND MAIN RESULTS: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. CONCLUSIONS: Future research and health care funding should be directed toward studying and evaluating these interventions.

Transcatheter valve in valve implantation for failed mitral and tricuspid bioprosthesis.

OBJECTIVE: We report our experience with the transapical transcatheter "Valve in valve" implantation (T-VIV) in patients with a failed mitral or tricuspid bioprosthesis; we briefly review the pertinent literature, and discuss some technical aspects of this procedure. BACKGROUND: Redo valve surgery for failure of a mitral or tricuspid bioprosthesis might become extremely challenging, both because of the patients' condition, which is frequently poor, and for the technical aspects of the operation itself, that can be very demanding. T-VIV has been widely employed with good results for the treatment of aortic bioprosthesis failure, and could represent an attractive option in this setting. METHODS: Four patients with multiple comorbidities (age: 63-83 years; logistic Euroscore: 37.2-81.5) underwent T-VIV at our institution for failure of a mitral [3] or tricuspid [1] bioprosthesis. A 26 mm Sapien valve was used in all cases. All the mitral procedures were performed via a transapical approach. The tricuspid procedure was performed via a transjugular approach. RESULTS: The first mitral procedure was complicated by the splaying of the xenograft stents and embolization of the valve. The procedure was converted to conventional surgery, and the patient died on postoperative day 1. In the subsequent procedures, the valve was positioned more atrially, and was fixed to the malfunctioning xenograft sewing ring. All subsequent procedures were successful, all patients were discharged home and were alive and well at follow-up. CONCLUSIONS: The results of T-VIV procedure in the mitral position have been suboptimal, and four of the sixteen patients reported to date died. However, all patients were extremely diseased, and some of the reported failures were related to amendable technical factors relative to the surgical access or to the valve deployment technique. With increasing experience, this procedure might become indicated as an alternative to conventional surgery in selected patients, encouraging increased use of bioprosthesis, and marking a pivotal change in the management of valvular disease.

Initial results of clinical trial with a new left ventricular assist device (LVAD) providing synchronous pulsatile flow.

OBJECTIVES: A multicentric European Clinical Study is ongoing to evaluate safety and efficacy of a new pulsatile implantable LVAD (BestBeat), smaller and lighter than similar devices, capable of providing synchronous and counterpulsating flow with respect to the LV of end-stage heart failure patients. Preliminary clinical results are reported. METHODS: The new BestBeat LVAD was used, consisting of an implantable pulsatile blood pump, electromechanically driven by a ball screw mechanism, and a wearable electronic controller and power sources. The clinical trial was conducted at 5 european centers. Adult patients affected by CHF in NYHA Class IV despite optimized medical treatment were enrolled. The primary study endpoint was survival at 90 days. Further study endpoints were maintenance of adequate LVAD pump flow and a minimum rate of adverse events during support. RESULTS: As of June 2008, 6 patients received the implant. Cumulative support time was 3.7 years, median support time 176 days. All patients who completed the study survived except for one, who died after 48 days, due to combined infection and cerebrovascular accident. Another two patients died: one from intracranial bleeding 113 days after implant, and one from septic shock after 123 days. Hemodynamic improvement with CI>2.0 l/min/m2 and recovery of end-organ function expressed by consistent improvement of BUN, creatinine and bilirubin were reached in all patients. No device failure was observed. There was no bleeding requiring re-exploration, no hemolysis and only two device-related infections (both in one patient). Neurologic events were reported, the most serious ones occurring in patients with pre-implant respiratory and kidney failure. Three patients were discharged home. Two patients were successfully transplanted, one after 6 months and one after 13 months on device. CONCLUSIONS: Good performance and efficacy of the device were observed; the endpoints of the study were achieved, and its safety was consistent with expectations. The ongoing study will allow further conclusions to be drawn.

Minimally invasive mitral valve surgery via right minithoracotomy.

From early experience in cardiac surgery on the mitral valve, access was gained in different ways: through left and right antero-lateral extended thoracotomy for closed and correspondingly for open mitral commissurotomy, from right parasternal access with rib resection, and via median sternotomy. Median sternotomy remains the most common approach for mitral valve procedures, such as replacement or repair, allowing good visualisation, exposure and working field. Applying the largely spread access as median sternotomy, surgeons always wanted to overcome the necessity of large incisions, get a better surgical view, to dissect with better respect to structural integrity and have better aesthetic results. Enhanced understanding of surgical bases and technological development sourced a breakthrough in minimally-invasive approach for mitral valve surgery, offering several advantages such as less postoperative pain, lower morbidity and mortality, faster recovery and shorter hospital stay. In an effort to share the institutional experience in less invasive surgery, this article demonstrates our approach in mitral valve repair through a right minithoracotomy in the 3rd or 4th intercostal space.

The double balloon cannula: a means to prevent backward flow of retrograde cardioplegia to the right atrium.

Retrograde cardioplegia (RC) delivery may result in suboptimal myocardial protection, due to leakage of cardioplegia to the right atrium. This study was undertaken to assess the efficacy of a double balloon cannula (DBC) occluding the coronary sinus ostium during RC. Fifteen patients were randomly assigned to receive RC via a conventional cannula or via the DBC. Cardioplegia was started at 200 ml/min, and the flow rate (Q) was adjusted to obtain a perfusion pressure (P) of 25-40 mmHg. Blood samples were collected at 13 different time points. The CPK-MB and TnI levels were measured on each sample. The use of the DBC was associated with increased P (P=0.03) at a lower Q (P=0.02). The CK-MB levels were significantly increased in both groups (P<0.0001). However, the use of the DBC was associated with lower levels of CK-MB (P=0.002). A similar trend was observed for the TnI levels (peak 5.1+/-1.8 ng/ml vs. 8.7+/-5 ng/ml, P=0.11). Occlusion of the coronary sinus ostium improved the hemodynamic efficiency of the RC, and this resulted in reduced perioperative ischemic myocardial damage.

Supplemental nitric oxide and its effect on myocardial injury and function in patients undergoing cardiac surgery with extracorporeal circulation.

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory response that may contribute to clinical morbidity. Gaseous nitric oxide at relatively low concentrations may elicit peripheral anti-inflammatory effects in addition to a reduction of pulmonary resistances. We examined the effects of 20 ppm of inhaled nitric oxide administered for 8 hours during and after cardiopulmonary bypass. METHODS AND RESULTS: Twenty-nine consecutive patients undergoing aortic valve replacement combined with aortocoronary bypass were randomly allocated to either 20 ppm of inhaled nitric oxide (n = 14) or no additional inhalatory treatment (n = 15). Blood samples for total creatine kinase, creatine kinase MB fraction, and troponin I measurements were collected at 4, 12, 24, and 48 hours postsurgery. In addition, we collected perioperative blood samples for measurements of circulating nitric oxide by-products and brain natriuretic peptide. Soluble P-selectin was analyzed in blood samples withdrawn from the coronary sinus before and after aortic clamping. The area under the curve of creatine kinase MB fraction (P =.03), total creatine kinase (P =.04), and troponin I (P =.04) levels were significantly decreased in the nitric oxide-treated patients. Moreover, in the same group we observed blunted P-selectin and brain natriuretic peptide release (P =.01 and P =.02, respectively). Nitric oxide inhalation consistently enhanced nitric oxide metabolite levels (P =.01). CONCLUSIONS: Nitric oxide, when administered as a gas at low concentration, is able to blunt the release of markers of myocardial injury and to antagonize the left ventricular subclinical dysfunction during and immediately after cardiopulmonary bypass. The organ protection could be mediated, at least in part, by its anti-inflammatory properties.