Calcium administration In patients undergoing CardiAc suRgery under cardiopulmonary bypasS (ICARUS trial): Rationale and design of a randomized controlled trial.

INTRODUCTION: Weaning from cardiopulmonary bypass (CPB) is a critical step of any cardiac surgical procedure and often requires pharmacologic intervention. Calcium ions are pivotal elements for the excitation-contraction coupling process of cardiac myocytes. Thus, calcium administration might be helpful during weaning from CPB. METHODS: We describe a multicenter, placebo-controlled, double blind randomized clinical trial to assess the effect of calcium chloride on the need for inotropic support among adult patients during weaning from CPB. The experimental group (409 patients) will receive 15 mg/kg of calcium chloride. The control group (409 patients) will receive an equivalent volume of 0.9% sodium chloride. Both drugs will be administered intravenously as a bolus at the beginning of weaning from CPB. RESULTS: The primary outcome will be the need for inotropic support between termination of CPB and completion of surgery. Secondary outcomes will be: duration of inotropic support, vasoactive-inotropic score 30 min after transfer to intensive care unit and on postoperative day 1, plasma alpha-amylase on postoperative day 1, plasma Ca2+ concentration immediately before and 10-15 min after calcium chloride administration, non-fatal myocardial infarction, blood loss on postoperative day 1, need for transfusion of red blood cells, signs of myocardial ischemia on electrocardiogram after arrival to intensive care unit, all-cause mortality at 30 days or during hospital stay if this is longer than 30 days. DISCUSSION: This trial is designed to assess whether intravenous calcium chloride administration could reduce the need for inotropic support after cardiopulmonary bypass weaning among adults undergoing cardiac surgery.

Clinical practice recommendations on the management of perioperative cardiac arrest: A report from the PERIOPCA Consortium.

BACKGROUND: Perioperative cardiac arrest is a rare complication with an incidence of around 1 in 1400 cases, but it carries a high burden of mortality reaching up to 70% at 30 days. Despite its specificities, guidelines for treatment of perioperative cardiac arrest are lacking. Gathering the available literature may improve quality of care and outcome of patients. METHODS: The PERIOPCA Task Force identified major clinical questions about the management of perioperative cardiac arrest and framed them into the therapy population [P], intervention [I], comparator [C], and outcome [O] (PICO) format. Systematic searches of PubMed, Embase, and the Cochrane Library for articles published until September 2020 were performed. Consensus-based treatment recommendations were created using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The strength of consensus among the Task Force members about the recommendations was assessed through a modified Delphi consensus process. RESULTS: Twenty-two PICO questions were addressed, and the recommendations were validated in two Delphi rounds. A summary of evidence for each outcome is reported and accompanied by an overall assessment of the evidence to guide healthcare providers. CONCLUSIONS: The main limitations of our work lie in the scarcity of good quality evidence on this topic. Still, these recommendations provide a basis for decision making, as well as a guide for future research on perioperative cardiac arrest.

Effect of intraoperative dexamethasone on major complications and mortality among infants undergoing cardiac surgery The DECISION Randomized Clinical Trial

IMPORTANCE Corticosteroids are widely used in pediatric cardiac surgery to blunt systemic inflammatory response and to reduce complications; nevertheless, their clinical efficacy is uncertain. OBJECTIVE To determine whether intraoperative administration of dexamethasone is more effective than placebo for reducing major complications and mortality during pediatric cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS The Intraoperative Dexamethasone in Pediatric Cardiac Surgery was an investigator-initiated, double-blind, multicenter randomized trial that involved 4 centers in China, Brazil, and Russia. A total of 394 infants younger than 12 months, undergoing cardiac surgery with cardiopulmonary bypass were enrolled from December 2015 to October 2018, with follow-up completed in November 2018. INTERVENTIONS The dexamethasone group (n = 194) received 1mg/kg of dexamethasone; the control group (n = 200) received an equivolume of 0.9%sodium chloride intravenously after anesthesia induction. MAIN OUTCOMES AND MEASURES The primary end pointwas a composite of death, nonfatalmyocardial infarction, need for extracorporeal membrane oxygenation, need for cardiopulmonary resuscitation, acute kidney injury, prolonged mechanical ventilation, or neurological complications within 30 days after surgery. There were 17 secondary end points, including the individual components of the primary end point, and duration of mechanical ventilation, inotropic index, intensive care unit stay, readmission to intensive care unit, and length of hospitalization. RESULTS All of the 394 patients randomized (median age, 6 months; 47.2%boys) completed the trial. The primary end point occurred in 74 patients (38.1%) in the dexamethasone group vs 91 patients (45.5%) in the control group (absolute risk reduction, 7.4%; 95%CI, −0.8%to 15.3%; hazard ratio, 0.82; 95%CI, 0.60 to 1.10; P = .20). Of the 17 prespecified secondary end points, none showed a statistically significant difference between groups. Infections occurred in 4 patients (2.0%) in the dexamethasone group vs 3 patients (1.5%) in the control group. CONCLUSIONS AND RELEVANCE Among infants younger than 12 months undergoing cardiac surgery with cardiopulmonary bypass, intraoperative administration of dexamethasone, compared with placebo, did not significantly reduce major complications and mortality at 30 days. However, the study may have been underpowered to detect a clinically important difference.

Effect of Intraoperative Dexamethasone on Major Complications and Mortality Among Infants Undergoing Cardiac Surgery: The DECISION Randomized Clinical Trial.

Importance: Corticosteroids are widely used in pediatric cardiac surgery to blunt systemic inflammatory response and to reduce complications; nevertheless, their clinical efficacy is uncertain. Objective: To determine whether intraoperative administration of dexamethasone is more effective than placebo for reducing major complications and mortality during pediatric cardiac surgery. Design, Setting, and Participants: The Intraoperative Dexamethasone in Pediatric Cardiac Surgery was an investigator-initiated, double-blind, multicenter randomized trial that involved 4 centers in China, Brazil, and Russia. A total of 394 infants younger than 12 months, undergoing cardiac surgery with cardiopulmonary bypass were enrolled from December 2015 to October 2018, with follow-up completed in November 2018. Interventions: The dexamethasone group (n = 194) received 1 mg/kg of dexamethasone; the control group (n = 200) received an equivolume of 0.9% sodium chloride intravenously after anesthesia induction. Main Outcomes and Measures: The primary end point was a composite of death, nonfatal myocardial infarction, need for extracorporeal membrane oxygenation, need for cardiopulmonary resuscitation, acute kidney injury, prolonged mechanical ventilation, or neurological complications within 30 days after surgery. There were 17 secondary end points, including the individual components of the primary end point, and duration of mechanical ventilation, inotropic index, intensive care unit stay, readmission to intensive care unit, and length of hospitalization. Results: All of the 394 patients randomized (median age, 6 months; 47.2% boys) completed the trial. The primary end point occurred in 74 patients (38.1%) in the dexamethasone group vs 91 patients (45.5%) in the control group (absolute risk reduction, 7.4%; 95% CI, -0.8% to 15.3%; hazard ratio, 0.82; 95% CI, 0.60 to 1.10; P = .20). Of the 17 prespecified secondary end points, none showed a statistically significant difference between groups. Infections occurred in 4 patients (2.0%) in the dexamethasone group vs 3 patients (1.5%) in the control group. Conclusions and Relevance: Among infants younger than 12 months undergoing cardiac surgery with cardiopulmonary bypass, intraoperative administration of dexamethasone, compared with placebo, did not significantly reduce major complications and mortality at 30 days. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02615262.

Current Practice of Calcium Use During Cardiopulmonary Bypass Weaning: Results of an International Survey.

OBJECTIVES: To describe international practices on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. DESIGN: Multiple-choice survey on current practice of CPB weaning. SETTING: Online survey using the SurveyMonkey platform. PARTICIPANTS: Departments of cardiac anesthesiology worldwide. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88 of 100 = 88%) administer calcium salts intraoperatively: 71 of 100 (71%) are using these drugs for CPB weaning and 78 of 100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58 of 88) of respondents use calcium chloride, 22% (19 of 88) use calcium gluconate, and 12% (11 of 88) use both drugs. Calcium salts are routinely used during normal (47 of 71 centers = 66%) and difficult (59 of 71 centers = 83%) weaning from CPB. Doses of 5 to 15 mg/kg during termination of CPB were used by 55 of 71 centers (77%) either by bolus (39 of 71, 55%) or over a time period longer than 1 minute (32 of 71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), and calcium is the second one, used by 23 out of 100 centers (23%). CONCLUSION: This survey demonstrates that the majority of cardiac centers use calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of drug, dose, and modality of drug administration.

Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a Multicenter Randomized Trial.

OBJECTIVE: Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence in a high-risk cardiac surgical population. DESIGN: Post hoc analysis of a multicenter randomized trial. SETTING: Cardiac surgery operating rooms and intensive care units of 14 centers in 3 countries. PARTICIPANTS: The study comprised 90 patients who underwent mitral valve surgery with an estimated glomerular filtration rate <60 mL/min/1.73 m2 and perioperative myocardial dysfunction. INTERVENTIONS: Patients were assigned randomly to receive levosimendan (0.025-0.2 µg/kg/min) or placebo in addition to standard inotropic treatment. MEASUREMENTS AND MAIN RESULTS: Forty-six patients were assigned to receive levosimendan and 44 to receive placebo. Postoperative AKI occurred in 14 (30%) patients in the levosimendan group versus 23 (52%) in the placebo group (absolute difference -21.8; 95% confidence interval -41.7 to -1.97; p = 0.035). The incidence of major complications also was lower (18 [39%]) in the levosimendan group versus that in the placebo group (29 [66%]) (absolute difference -26.8 [-46.7 to -6.90]; p = 0.011). A trend toward lower serum creatinine at intensive care unit discharge was observed in the levosimendan group (1.18 [0.99-1.49] mg/dL) versus that in the placebo group (1.39 [1.05-1.76] mg/dL) (95% confidence interval -0.23 [-0.49 to 0.01]; p = 0.07). CONCLUSIONS: Levosimendan may improve renal outcome in cardiac surgery patients with chronic kidney disease undergoing mitral valve surgery who develop perioperative myocardial dysfunction. Results of this exploratory analysis should be investigated in future properly designed randomized controlled trials.

Levosimendan for Hemodynamic Support after Cardiac Surgery.

BACKGROUND: Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 µg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS: The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS: In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).

Evaluation of nutritional screening tools among patients scheduled for heart valve surgery.

BACKGROUND AND AIM OF THE STUDY: The study aim was to detect the most sensitive nutritional screening tool and to assess its prognostic value with regards to an adverse clinical course in patients with heart valve disease undergoing cardiopulmonary bypass (CPB). METHODS: This prospective cohort study included 441 adult patients who were screened using four nutritional screening tools: Nutritional Risk Screening 2002 (NRS-2002); Malnutrition Universal Screening Tool (MUST); Mini Nutritional Assessment (MNA); and Short Nutritional Assessment Questionnaire (SNAQ). Nutritional assessment was performed using a Subjective Global Assessment (SGA). In-hospital mortality, postoperative complications, and duration of hospital stay were each analyzed. RESULTS: With regards to the detection of malnutrition, the sensitivities of MUST, SNAQ, MNA and NRS-2002 were 100%, 92%, 84.6% and 43.6%, respectively. Malnutrition identified by MUST and MNA were associated with postoperative complications (OR 1.63, p = 0.033 and OR 1.6, p = 0.035) and prolonged hospitalization (OR 1.57, p = 0.048 and OR 1.7, p = 0.02). According to multivariate logistic regression analysis, along with well-known age and duration of CPB, malnutrition identified by MUST and MNA was associated with a risk of development of complications (OR 1.6, p = 0.049 and OR 1.6, p = 0.04, respectively). The sensitivities of SNAQ, MUST, NRS-2002 and MNA with regards to postoperative complications were 26.8%, 28.8%, 10%, and 31.6%, respectively. CONCLUSION: The MUST tool is preferable with regards to the detection of malnutrition. Both, MUST and MNA independently predicted postoperative complications. SNAQ and NRS-2002 proved insensitive with regards to the postoperative course among patients with heart valve disease who were scheduled for cardiothoracic surgery.

Prognostic value of nutritional screening tools for patients scheduled for cardiac surgery.

OBJECTIVES: The aim of this study was to assess the prognostic value of different nutritional screening tools in patients undergoing cardiopulmonary bypass, with regard to adverse clinical outcome. METHODS: This prospective cohort study analysed 1193 adult patients who underwent cardiopulmonary bypass. Patients were screened using five nutritional screening tools: Subjective Global Assessment (SGA), Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), Mini-Nutritional Assessment (MNA) and Short Nutritional Assessment Questionnaire (SNAQ). In-hospital mortality, postoperative complications, length of stay in intensive care unit and length of hospitalization were analysed. Multivariate backward logistic regression analysis was used to assess the independent predictive value of the studied screening tools. RESULTS: In accordance with univariate analysis, malnutrition detected by SNAQ, MUST, NRS-2002 and MNA was associated with postoperative complications (odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.3-2.4; OR 1.9, 95% CI 1.4-2.6; OR 1.8, 95% CI 1.2-2.9 and OR 1.9, 95% CI 1.4-2.6). Malnutrition detected by MUST, NRS-2002, MNA and SGA was associated with intensive care unit stay >2 days (OR 1.5, 95% CI 1.1-2.1; OR 2.3, 95% CI 1.5-3.7; OR 1.7, 95% CI 1.2-2.2 and OR 2.7, 95% CI 1.6-4.6). Prolonged hospitalization (>20 days) was predicted by SNAQ, MUST and MNA (OR 1.4, 95% CI 1-1.9; OR 1.6, 95% CI 1.2-2.2 and OR 1.6, 95% CI 1.2-2.2). In accordance with multivariate analysis, only MUST and MNA independently predicted postoperative complications (OR 1.6, 95% CI 1.1-2.3 and OR 1.6, 95% CI 1.1-2.2). Other independent factors influencing postoperative complications were well-known logistic EuroSCORE (OR 1.06, 95% CI 1-1.1) and the duration of cardiopulmonary bypass in minutes (OR 1.01, 95% CI 1-1.01). CONCLUSIONS: MUST and MNA both have independent predictive values with regard to postoperative complications. Taking into account simplicity, MUST is preferable for the cardiac surgical population.

Evaluation of nutritional screening tools for patients scheduled for cardiac surgery.

OBJECTIVE: The aim of this study was to assess the prognostic value of different nutritional screening tools in patients undergoing cardiopulmonary bypass with regard to an adverse clinical course. METHODS: This prospective cohort study analyzed 894 adult patients who underwent cardiopulmonary bypass. Patients were screened using four nutritional screening tools: Nutritional Risk Screening 2002 (NRS-2002), the Malnutrition Universal Screening Tool (MUST), the Mini-Nutritional Assessment (MNA), and the Short Nutritional Assessment Questionnaire (SNAQ). Nutritional status was assessed using the Subjective Global Assessment. In-hospital mortality, postoperative complications, length of stay in the intensive care unit, and length of hospitalization were analyzed. RESULTS: The sensitivities of the SNAQ, MUST, and NRS-2002 to detect the malnutrition confirmed by the Subjective Global Assessment were 91.5%, 97.9%, and 38.3%, respectively, and the MNA showed a sensitivity of 81.8% for the elderly. Malnutrition detected by the SNAQ, MUST, and NRS-2002 was associated with postoperative complications (odds ratios [ORs] 1.75, 1.98, and 1.82, respectively) and a stay in the intensive care unit longer than 2 d (ORs 1.46, 1.56, and 2.8). Malnutrition as detected by the SNAQ and MUST was also associated with prolonged hospitalization (ORs 1.49 and 1.59). According to multivariate logistic regression analysis, postoperative complications were independently predicted by the European System for Cardiac Operative Risk Evaluation (OR 1.1, P < 0.0001), cardiopulmonary bypass time (OR 1.01, P < 0.0001), and malnutrition identified by the MUST (OR 1.2, P = 0.01). CONCLUSION: The MUST independently predicts postoperative complications. The SNAQ and MUST have comparable accuracy in detecting malnutrition. Whether preoperative nutritional therapy would improve the outcome in malnourished patients needs to be studied.

Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients.

OBJECTIVE: To test the hypothesis that levosimendan is more effective than intra-aortic balloon pump (IABP) support in cardiac surgical patients with low left ventricular ejection fraction to decrease cardiac troponin I levels (primary endpoint) and improve hemodynamics. DESIGN: Prospective randomized trial. SETTING: Tertiary cardiothoracic referral center. PARTICIPANTS: Ninety patients with coronary artery disease and left ventricular ejection fraction <35% who underwent surgery with cardiopulmonary bypass. INTERVENTION: Patients were assigned randomly to 1 of 3 groups. Group A received a prophylactic IABP one day before surgery. Group B received a prophylactic IABP one day before surgery and a levosimendan infusion at a dose of 0.1 µg/kg/min with an initial bolus (12 µg/kg for 10 minutes) after anesthesia induction. Group C received a levosimendan infusion at a dose of 0.1 µg/kg/min with an initial bolus (12 µg/kg for 10 minutes) after anesthesia induction. Hemodynamic and biochemical data and rate of complications were analyzed. MEASUREMENTS AND MAIN RESULTS: The cardiac troponin I level in group C 6 hours after surgery was lower than in group A (p = 0.048). The cardiac index in group A was significantly lower than in groups B and C. The intensive care unit stay was significantly shorter in group C than in groups A and B (p = 0.001). The need for inotropic support, the rate of complications, and mortality among groups did not differ. CONCLUSIONS: The infusion of levosimendan after anesthesia induction in cardiac surgical patients contributes to lower cardiac troponin I levels and improved hemodynamics compared with a preoperative IABP.

Levosimendan vs. intra-aortic balloon pump in high-risk cardiac surgery.

The purpose of our study was to compare the efficiency of levosimendan and preventive intra-aortic balloon pump in high-risk cardiac patients (left ventricular ejection fraction <35%) operated under cardiopulmonary bypass. In 20 patients, intra-aortic balloon pump was started 16-18 h before surgery; another 20 had a levosimendan infusion starting after induction of anesthesia with an initial bolus of 12 µg·kg(-1) for 10 min, followed by 0.1 µg·kg(-1)·min(-1) for 24 h. Postoperative complications, hemodynamics, and markers of cardiac damage were analyzed. In the levosimendan group, cardiac index was significantly higher 5 min after cardiopulmonary bypass, at the end of the operation, 2 and 4 h after perfusion, compared to the intra-aortic balloon pump group. The level of troponin I in the levosimendan group was significantly lower at 6 h after the operation. Intensive care unit stay was significantly shorter in the levosimendan group. It was concluded that the use of levosimendan in high-risk cardiac patients is as effective as intra-aortic balloon pump, in terms of maintaining stable hemodynamic during and after operations under cardiopulmonary bypass. The lower level of troponin I at 6 h postoperatively suggests cardioprotective properties of levosimendan, but requires further investigation.

Preoperative total lymphocyte count in peripheral blood as a predictor of poor outcome in adult cardiac surgery.

OBJECTIVE: The aim of this study was to investigate the prognostic value of the preoperative total lymphocyte count in peripheral blood as a predictor of postoperative complications and mortality in cardiac surgery. DESIGN: A retrospective, observational study. SETTING: The Novosibirsk State Research Institute of Circulation Pathology (single institution). PARTICIPANTS: All adults undergoing primary cardiopulmonary bypass in 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort size was 1,368 patients operated upon with cardiopulmonary bypass. Patient characteristics, hospital mortality, postoperative complications, ventilation time, intensive care unit, and hospital stay were analyzed. A preoperative total lymphocyte count <1,500 cells/µL was associated with significantly higher mortality by univariate (p < 0.0001) and multivariate (p < 0.044) analyses. A low preoperative total lymphocyte count was associated with more frequent inotropic support (p < 0.001); postoperative heart arrhythmia (p < 0.001); dialysis-dependent acute renal failure (p < 0.001); and a prolonged ventilation time (p = 0.001), intensive care unit stay (p < 0.001), and hospital stay (p = 0.007). CONCLUSIONS: A low preoperative total lymphocyte count in peripheral blood is a useful prognostic criterion for the evaluation of a complicated postoperative period in cardiac patients operated under cardiopulmonary bypass.