Heparin-resistance in AL amyloidosis: a case report.

BACKGROUND: Non-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance. CASE PRESENTATION: We present a fatal case of a 70-yr-old male-patient undergoing cardiac-surgery in which refractory heparin-resistance was observed. The massive AL amyloidosis found at autopsy is thought to be responsible and illustrates that awareness and knowledge of the etiology and perioperative strategies of non-AT-III mediated heparin-resistance is important. CONCLUSION: For anticoagulation during cardiopulmonary bypass surgery in case of a non-AT-III medicated heparin resistance, we refer to the decision tree added to this manuscript and if necessary to consider direct thrombin inhibitors, such as bivalirudin or argatroban, as it bypasses the complexing pathway.

Preoperative anaemia and outcome after elective cardiac surgery: a Dutch national registry analysis.

BACKGROUND: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. METHODS: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. RESULTS: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4-1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3-1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4-2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. CONCLUSIONS: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes.

Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study.

OBJECTIVES: To determine the safety and efficacy of human chorionic gonadotropin hormone-derivative EA-230 in cardiac surgery patients. Cardiac surgery induces systemic inflammation and may impair renal function, affecting patient outcome. EA-230 exerted immunomodulatory and renoprotective effects in preclinical models and was safe and showed efficacy in phase I and II human studies. DESIGN: Double-blinded, placebo-controlled, randomized study. SETTING: Collaboration of the Cardiothoracic Surgery, Anesthesiology, and the Intensive Care departments of a tertiary hospital in the Netherlands. PATIENTS: One hundred eighty patients undergoing an on-pump coronary artery bypass procedure with or without concomitant valve surgery. INTERVENTIONS: Ninety mg/kg/hr EA-230 or placebo administered during surgery. MEASUREMENTS AND MAIN RESULTS: During the study, no safety concerns emerged. EA-230 did not modulate interleukin-6 plasma concentrations (area under the curve 2,730 pg/mL × hr [1,968-3,760] vs 2,680 pg/mL × hr [2,090-3,570] for EA-230 and placebo group, respectively; p = 0.80). Glomerular filtration rate increased following surgery (mean ± sem increase in the EA-230 vs placebo groups: glomerular filtration rateiohexol measured using iohexol plasma clearance: 19 ± 2 vs 16 ± 2 mL/min/1.73 m2; p = 0.13 and estimated glomerular filtration rate with the Modification of Diet in Renal Disease equation using creatinine: 6 ± 1 vs 2 ± 1 mL/min/1.73 m2; p = 0.01). The "injury" stage of the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria for acute kidney injury was 7% in the EA-230 group versus 18% in the placebo group (p = 0.07). In addition, EA-230-treated patients had a less positive fluid balance compared with placebo-treated patients (217 ± 108 vs 605 ± 103 mL; p = 0.01), while the use of vasoactive agents was similar in both groups (p = 0.39). Finally, hospital length of stay was shorter in EA-230 treated patients (8 d [7-11] vs 10 d [8-12]; p = 0.001). Efficacy results were more pronounced in patients that had longer duration of surgery and thus longer duration of study drug infusion. CONCLUSIONS: EA-230 was safe in patients undergoing on-pump cardiac surgery. It did not modulate interleukin-6 plasma concentrations but appeared to exert beneficial renal and cardiovascular effects and shortened in-hospital length of stay.

Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial.

BACKGROUND: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. METHODS: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. RESULTS: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. CONCLUSIONS: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Impact of Intraoperative Hypotension During Cardiopulmonary Bypass on Acute Kidney Injury After Coronary Artery Bypass Grafting.

OBJECTIVE: The aim of this study was to investigate whether acute kidney injury (AKI) after coronary artery bypass grafting can be attributed to intraoperative hypotension during cardiopulmonary bypass (IOH-CPB). DESIGN: Retrospective analysis. SETTING: Tertiary-care hospital. PARTICIPANTS: Patients undergoing on-pump coronary artery bypass grafting from June 2011 to January 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: IOH-CPB was defined as blood pressure below several absolute and relative mean arterial pressure (MAP) thresholds and as the area under the curve for absolute MAP thresholds. AKI was defined as an absolute increase in serum creatinine of≥26 µmol/L within 48 hours or an increase to 150% or more within 7 days of surgery. Poisson regression with robust standard errors both before and after adjustment for confounders was used. Of the 1,891 patients included, 386 (20%) developed AKI. In univariable analysis, all IOH-CPB thresholds defined as a MAP of 50 mmHg or less and as a decrease in MAP of 60% from baseline were associated with a 1.07-to-1.11 times increased risk of AKI per 10 minutes of IOH-CPB (p<0.01). After adjustment for potential confounders, IOH-CPB, irrespective of the definition chosen, was not associated with an increased risk of AKI. CONCLUSIONS: In the authors' study population, univariable analysis showed an association of IOH-CPB with AKI in patients undergoing isolated CABG, but this relationship disappeared after correction for well-known risk factors for AKI.

The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission: Longitudinal Follow-Up of a Randomized Controlled Trial.

OBJECTIVE: Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder and depression. Perioperatively administered corticosteroids potentially alter the risk of development of these psychiatric conditions, by affecting the hypothalamic-pituitary-adrenal axis. However, findings of previous studies are inconsistent. We aimed to assess the effect of a single dose of dexamethasone compared with placebo on symptoms of posttraumatic stress disorder and depression and health-related quality of life after cardiac surgery and ICU admission. DESIGN: Follow-up study of a randomized clinical trial. SETTING: Five Dutch heart centers. PATIENTS: Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial. INTERVENTIONS: A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way. MEASUREMENTS AND MAIN RESULTS: Symptoms of posttraumatic stress disorder, depression, and health-related quality of life were assessed with validated questionnaires 1.5 years after randomization. Data were available for 1,125 patients (90.4%); of which 561 patients received dexamethasone and 564 patients received placebo. Overall, the prevalence of psychopathology was not influenced by dexamethasone. Posttraumatic stress disorder and depression were present in, respectively, 52 patients (9.3%) and 69 patients (12.3%) who received dexamethasone and in 66 patients (11.7%) and 78 patients (13.8%) who received placebo (posttraumatic stress disorder: odds ratio, 0.82; 95% CI, 0.55-1.20; p = 0.30; depression: odds ratio, 0.92; 95% CI, 0.64-1.31; p = 0.63). Subgroup analysis revealed a lower prevalence of posttraumatic stress disorder (odds ratio, 0.23; 95% CI, 0.07-0.72; p < 0.01) and depression (odds ratio, 0.29; 95% CI, 0.11-0.77; p < 0.01) in female patients after dexamethasone administration. Health-related quality of life did not differ between groups and was not associated with psychopathology. CONCLUSIONS: Overall, our findings suggest that exogenous administration of the glucocorticoid receptor agonist dexamethasone-compared with placebo-during cardiac surgery does not positively or negatively affect the prevalence of posttraumatic stress disorder and depression. However, in female patients, beneficial effects on the occurrence of posttraumatic stress disorder and depression may be present.

Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery.

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control: a randomized controlled trial.

INTRODUCTION: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. METHODS: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol--Glucose Regulation for Intensive care Patients (GRIP)--was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC15). ICU length of stay and mortality were observed as well. RESULTS: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC15 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC15 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). CONCLUSIONS: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. TRIAL REGISTRATION: ClinicalTrials.gov NCT00293592 . Registered 16 February 2006.

A novel approach to assess hemorrhagic shock severity using the arterially determined left ventricular isovolumic contraction period.

Recently, the ventilatory variation in pre-ejection period (ΔPEP) was found to be useful in the prediction of fluid-responsiveness of patients in shock. In the present study we investigated the behavior of the ventilation-induced variations in the systolic timing intervals in response to a graded hemorrhage protocol. The timing intervals studied included the ventilatory variation in ventricular electromechanical delay (ΔEMD), isovolumic contraction period (determined from the arterial pressure waveform, ΔAIC), pulse travel time (ΔPTT), and ΔPEP. ΔAIC and ΔPEP were evaluated in the aorta and carotid artery (annotated by subscripts Ao and CA) and were compared with the responses of pulse pressure variation (ΔPPAo) and stroke volume variation (ΔSV). The graded hemorrhage protocol, followed by resuscitation using norepinephrine and autologous blood transfusion, was performed in eight anesthetized Yorkshire X Landrace swine. ΔAICAo, ΔAICCA, ΔPEPAo, ΔPEPCA, ΔPPAo, ΔPPCA, and ΔSV showed significant increases during the graded hemorrhage and significant decreases during the subsequent resuscitation. ΔAICAo, ΔAICCA, ΔPEPAo, and ΔPEPCA all correlated well with ΔPPAo and ΔSV (all r ≥ 0.8, all P < 0.001). ΔEMD and ΔPTT did not significantly change throughout the protocol. In contrast with ΔPEPAo, which was significantly higher than ΔPEPCA (P < 0.01), ΔAICAo was not different from ΔAICCA. In conclusion, ventilation-induced preload variation principally affects the arterially determined isovolumic contraction period (AIC). Moreover, ΔAIC can be determined solely from the arterial pressure waveform, whereas ΔPEP also requires ECG measurement. Importantly, ΔAIC determined from either the carotid or aortic pressure waveform are interchangeable, suggesting that, in contrast with ΔPEP, ΔAIC may be site independent.

Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial.

CONTEXT: Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. OBJECTIVE: To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011. INTERVENTION: Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). MAIN OUTCOME MEASURES: A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. RESULTS: Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. CONCLUSION: In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00293592.

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial).

BACKGROUND: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome. METHODS/DESIGN: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year.Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%. DISCUSSION: The RICO-trial (the effect of Remote Ischemic Conditioning on atrial fibrillation and Outcome) is a randomized controlled multicenter trial, designed to investigate whether remote ischemic pre- and/or post-conditioning of the arm reduce the incidence of AF following CABG surgery. TRIAL REGISTRATION: ClinicalTrials.gov under NCT01107184.

The role of mast cell stabilization in treatment of postoperative ileus: a pilot study.

OBJECTIVES: Although postoperative ileus (POI) is considered multifactorial, intestinal inflammation resulting from manipulation-induced mast cell activation is recognized as an important pathophysiological mechanism. Therefore, mast cell stabilization may represent a new therapeutic approach to shortening POI. The aim of this paper was to study the effect of ketotifen, a mast cell stabilizer, on postoperative gastrointestinal transit in patients who underwent abdominal surgery. METHODS: In this pilot study, 60 patients undergoing major abdominal surgery for gynecological malignancy with standardized anesthesia were randomized to treatment with ketotifen (4 or 12 mg) or placebo. Patients were treated for 6 days, starting 3 days before surgery. Gastric emptying of liquids, selected as a primary outcome parameter, was measured 24 h after surgery using scintigraphy. Secondary end points were (scintigraphically assessed) colonic transit, represented as geometrical center of activity (segment 1(cecum) to 7(stool)) and clinical parameters. RESULTS: Gastric retention 1 h after liquid intake was significantly reduced by 12 mg (median 3% (1-7), P=0.01), but not by 4 mg ketotifen (18% (3-45), P=0.6) compared with placebo (16% (5-75)). Twenty-four hour colonic transit in placebo was 0.8 (0.0-1.1) vs. 1.2 (0.2-1.4) colon segments in the 12 mg ketotifen group (P=0.07). Abdominal cramps were significantly relieved in patients treated with 12 mg ketotifen, whereas other clinical parameters were not affected. CONCLUSIONS: Ketotifen significantly improves gastric emptying after abdominal surgery and warrants further exploration of mast cell stabilizers as putative therapy for POI.

Intraoperative real time three-dimensional transesophageal echocardiographic measurement of hemodynamic, anatomic and functional changes after aortic valve replacement.

The traditional intraoperative two-dimensional transesophageal echocardiography (2DTEE) has limitations in measuring left ventricular ejection fraction (LVEF) because measurements rely on geometric assumptions. The availability of online software and real time three-dimensional transesophageal echocardiography (RT3D-TEE) makes intraoperative LVEF measurements fast and easy. This is the first report of intraoperative measurement of LVEF and aortic valve area (AVA) by RT3-DTEE in a patient who received transcatheter-based transapical aortic valve implantation.

Intraoperative transesophageal echocardiography is beneficial for hemodynamic stabilization during left ventricular assist device implantation in children.

BACKGROUND: Mechanical circulatory support, with a left ventricular assist device (LVAD) is used in an increasing number of children for treatment of advanced heart failure as bridge-to-transplant. To date no data are available and no studies have defined the role of intraoperative transesophageal echocardiography (TEE) for hemodynamic stabilization during Centrimag Levitronix centrifugal pump implantation in children. METHODS: Children with therapy resistant heart failure, undergoing LVAD implantation using Berlin Heart Excor pediatric cannula connected to a Levitronix Centrifumag pump, are intraoperatively monitored using an Oldelft micromultiplane TEE. Intraoperative TEE is specially used to monitor right ventricular (RV) and left ventricular (LV) function, correct position of the cannulas and response to pharmacological treatment. RESULTS: In five consecutive patients RV function was assessed by TEE after starting LVAD Levitronix centrifugal pump. Initial RV failure presents with RV dilation and LV collapse. After titration of vasopressor and inotropic agents, RV contractility improved and thereby the filling of the LV. In one child, despite those measures the RV showed no improvement by TEE and a Levitronix right ventricular assist device to support the RV function was implanted as well. All patients could hemodynamically be stabilized before transport to the intensive care unit. CONCLUSION: The complex interaction of the RV and LV function and correct positioning of the cannula, during LVAD implantation in children with end-stage cardiac failure is improved by simultaneous visualization of cardiac performance of both ventricles and cannula positioning by means of intraoperative multiplane TEE.

Alveolar recruitment strategy and PEEP improve oxygenation, dynamic compliance of respiratory system and end-expiratory lung volume in pediatric patients undergoing cardiac surgery for congenital heart disease.

OBJECTIVE: Optimizing alveolar recruitment by alveolar recruitment strategy (ARS) and maintaining lung volume with adequate positive end-expiratory pressure (PEEP) allow preventing ventilator-induced lung injury (VILI). Knowing that PEEP has its most beneficial effects when dynamic compliance of respiratory system (Crs) is maximized, we hypothesize that the use of 8 cm H(2)O PEEP with ARS results in an increase in Crs and end-expiratory lung volume (EELV) compared to 8 cm H(2)O PEEP without ARS and to zero PEEP in pediatric patients undergoing cardiac surgery for congenital heart disease. METHODS: Twenty consecutive children were studied. Three different ventilation strategies were applied to each patient in the following order: 0 cm H(2)O PEEP, 8 cm H(2)O PEEP without an ARS, and 8 cm H(2)O PEEP with a standardized ARS. At the end of each ventilation strategy, Crs, EELV, and arterial blood gases were measured. RESULTS: EELV, Crs, and P(a)O(2)/FiO(2) ratio changed significantly (P < 0.001) with the application of 8 cm H2O + ARS. Mean P(a)CO(2)- PETCO(2) difference between 0 PEEP and 8 cm H2O PEEP + ARS was also significant (P < 0.05). CONCLUSION: An alveolar recruitment strategy with relative high PEEP significantly improves Crs, oxygenation, P(a)CO(2)- PETCO(2) difference, and EELV in pediatric patients undergoing cardiac surgery for congenital heart disease.

The Safety, Tolerability, and Effects on the Systemic Inflammatory Response and Renal Function of the Human Chorionic Gonadotropin Hormone-Derivative EA-230 Following On-Pump Cardiac Surgery (The EASI Study): Protocol for a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study.

BACKGROUND: The cardiac surgery-induced systemic inflammatory response may induce postoperative hemodynamic instability and impairment of renal function. EA-230, a linear tetrapeptide (A-Q-G-V), is derived from the beta chain of the human chorionic gonadotropin pregnancy hormone. It has shown immunomodulatory and renoprotective effects in several animal models of systemic inflammation. In phase 1 and phase 2a studies, these immunomodulatory effects were confirmed during human experimental endotoxemia, and EA-230 was found to have an excellent safety profile. OBJECTIVE: The objective of this first in-patient study is to test the safety and tolerability as well as the immunomodulatory and renoprotective effects of EA-230 in a proof-of-principle design in patients with systemic inflammation following on-pump cardiac surgery. METHODS: We describe a prospective, randomized, double-blind, placebo-controlled study in which 180 elective patients undergoing on-pump coronary artery bypass grafting, with or without concomitant valve surgery, are enrolled. Patients will be randomized in a 1:1 ratio and will receive either EA-230 (90 mg/kg/hour) or a placebo. These will be infused at the start of the surgical procedure until the end of the use of the cardiopulmonary bypass. The primary focus of this first-in-patient study will be on safety and tolerability of EA-230. The primary efficacy end point is the modulation of the inflammatory response by EA-230 quantified as the change in interleukin-6 plasma concentrations after surgery. The key secondary end point is the effect of EA-230 on renal function. The study will be conducted in 2 parts to enable an interim safety analysis by an independent data monitoring committee at a sample size of 60. An adaptive design is used to reassess statistical power halfway through the study. RESULTS: This study has been approved by the independent competent authority and ethics committee and will be conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, and European Directive 2001/20/CE regarding the conduct of clinical trials. Results of this study will be submitted for publication in a peer-reviewed scientific journal. Enrollment of this study commenced in July 2016, and results are expected at the end of 2018. CONCLUSIONS: This adaptive phase 2 clinical study is designed to test the safety and tolerability of EA-230 in patients undergoing cardiac surgery. In addition, efficacy end points focused on the effect of the systemic inflammatory response and renal function are investigated. TRIAL REGISTRATION: ClinicalTrials.gov NCT03145220; https://clinicaltrials.gov/ct2/show/NCT03145220 (Archived by WebCite at http://www.webcitation.org/74JPh8GNN). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11441.

Intraoperative real time three-dimensional transesophageal echocardiographic evaluation of right atrial tumor.

Right atrial myxomas are uncommon heart tumors that can simulate nonspecific symptoms, such as fever, paroxysmal palpitations, chronic anemia, weight loss, and may escape timely diagnosis until the development of severe complications due to embolism. We present a patient with a history of palpitations. In search for the source of palpitations, a 2D transthoracic echocardiography was performed, showing a right atrial mass. Real time three-dimensional transesophageal echocardiography (RT3DTEE) was performed intraoperative and demonstrated very accurate information about the size and the morphology of the tumor. This is the first case report of a right atrial myxoma visualized intraoperatively by RT3DTEE.

Usefulness of intraoperative real-time 3D transesophageal echocardiography in cardiac surgery.

BACKGROUND: Recent advances in three-dimensional (3D) echocardiography allow to obtain real-time 3D transesophageal (RT3DTEE) images intraoperatively. METHODS: Preoperative transthoracic echocardiography (TTE) revealed: hypertrophic ventricular septum (TTE:19.3 mm), systolic anterior motion (SAM) not causing obstruction and malcoaptation of the anterior mitral valve leaflet (AMVL), and posterior mitral valve leaflet (PMVL) with severe mitral regurgitation. RESULTS: Intraoperative TEE with a x7-2t MATRIX-array transducer (Philips, Andover, MA, USA) with a transducer frequency of x7-2 t mHz, connected to a iE33 (Philips), shows us that the main mechanism and site of regurgitation was an AMVL cleft. We also measured a 24.3-mm thickness of the ventricular septum and analyzing the 3D full volume acquisition revealed that there was no SAM. CONCLUSION: Intraoperative RT3DTEE permitted comprehensive 3D viewing of the mitral valve revealing the mechanism of mitral valve regurgitation, SAM, and the exact width of the hypertrophic ventricular septum.

Effectiveness of adherence to a preoperative antiplatelet and anticoagulation cessation protocol in cardiac surgery.

OBJECTIVES: Reduction of blood loss after cardiac surgery remains challenging. The effectiveness of adherence to a protocol on cessation of anticoagulants and platelet-inhibiting medications was investigated together with the influence of protocol violations on blood loss after surgery, use of blood products, surgical re-explorations and 30-day mortality. METHODS: Between 2009 and 2013, data were collected prospectively for all elective cardiac surgery procedures in adult patients (n = 1637). Two groups were distinguished: Group 1 adhered to the protocol for cessation or continuation of medication (n = 1287, 79%) and Group 2 violated the protocol (n = 350, 21%). RESULTS: Median blood loss was 300 ml (interquartile range 175-500 ml). Eighty patients underwent re-exploration due to blood loss (5%). Thirty-day mortality was 2% (n = 27). Protocol violation was associated with increased blood loss [median 275 ml (175-475 ml) vs 350 ml (250-612); P ≤ 0.001] and with increased average use of fresh frozen plasma (226 ml vs 139 ml; P << 0.00001), red blood cell transfusion (115 ml vs 87 ml; P = 0.081) and thrombocyte transfusions (52 ml vs 37 ml; P = 0.0082). The number of re-explorations (4% vs 6%; P = 0.39) and mortality risk (1% vs 2%; P = 0.72) did not differ. CONCLUSIONS: Balancing the benefit of continuing platelet inhibitors or anticoagulants versus cessation before surgery remains challenging. Adherence to the protocol will lead to lower blood loss and in a lower consumption of blood products although the decision to go for re-exploration and 30-day mortality does not differ compared with the protocol violation. Stopping medication does not lead to thromboembolic events.