Kaolin-activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: a prospective cohort study.

BACKGROUND AND AIMS: Several studies report the use of thromboelatography (TEG) to monitor coagulation in pediatric cardiac surgery. The aim of this study was to compare baseline and intraoperative TEG, TEG-functional fibrinogen, and standard coagulation assays in children with cyanotic and acyanotic congenital heart disease (CHD) undergoing cardiac surgery. METHODS: This is a prospective observational study of 63 children aged <24 months undergoing cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria included preoperative anticoagulant therapy and hepatic failure. We collected blood at anesthesia induction (T1), at lowest temperature after CPB start (T2), and after heparin neutralization (T3). Coagulation was evaluated by TEG (reaction time [R]), k, alpha-angle, maximum amplitude (MA), MA-fibrinogen (MA-fib), and by standard coagulation assays (prothrombin time, activated partial thromboplastin time, fibrinogen level, platelet [PLT] count). RESULTS: Sixty-three patients were enrolled (38 cyanotic and 25 acyanotic). Median age was 4 [IQR 2-6] months and median weight was 5 [IQR 3.7-6.5] kg. Most common surgeries were: ventricular septal defect repair (n = 13), Fallot correction (n = 11), and arterial switch operation (n = 10). Cyanotic and acyanotic children were well matched: R, k, MA, and MA-fib at T1, T2, and T3 were not significantly different between cyanotic and acyanotic children. At T2, significant correlations were showed between MA and PLT count (r = 0.4; P = 0.0008) and k and plasma fibrinogen level (r = -0.54; P < 0.0001). At T3, significant correlations were showed between MA and PLT count (r = 0.5; P < 0.0001), G and PLT count (r = 0.6; P < 0.0001), and MA-fib and plasma fibrinogen level (r = 0.5; P = 0.002). CONCLUSIONS: According to our findings, cyanosis does not affect TEG parameters in children with CHD. PLT count and plasma fibrinogen significantly correlated (are significantly associated) with MA and MA-fib respectively, suggesting that use of TEG after protamine administration may be prompted for improved hemostatic monitoring in the perioperative phase.

Evaluation of Endotoxemia After Pediatric Cardiac Surgery With the Endotoxin Activity Assay: An Exploratory Prospective Cohort Study.

OBJECTIVE: Children with congenital heart diseases undergoing surgery with cardiopulmonary bypass are exposed to a high risk of perioperative endotoxemia. The aim of our study was to prospectively evaluate endotoxin assay activity reference levels during the postoperative phase of infants undergoing cardiac surgery for congenital heart disease and to assess their association with perioperative variables and postoperative infections. DESIGN: Prospective exploratory single-center cohort study. SETTING: Tertiary pediatric cardiac ICU. PATIENTS: Infants undergoing cardiac surgery with cardiopulmonary bypass were enrolled. Exclusion criteria were preoperative suspected or confirmed infection, the need for extracorporeal membrane oxygenation or a ventricular assist device in any perioperative phase, surgery for heart transplantation, and/or urgent surgery. INTERVENTIONS: Serial measurements of endotoxin assay activity were performed at baseline, pediatric cardiac ICU arrival, postoperative day 1 and 2. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were enrolled. Overall, 14 of 25 patients (58%) presented at least one endotoxin assay activity level greater than 0.4 during the study period (normal level is < 0.4). Endotoxin assay activity levels tended to significantly increase from baseline to postoperative day 1 and 2 and from pediatric cardiac ICU arrival to postoperative day 2 (p < 0.0001). Endotoxin assay activity greater than 0.6 predicted Gram-negative infections with a sensitivity of 0.40, a specificity of 0.95, a positive predictive value of 0.66, and a negative predictive value of 0.86. At multivariable regression, endotoxin assay activity on postoperative day 1 resulted independently associated with cardiopulmonary bypass duration, lactate, temperature peak, and vasoactive inotropic score at pediatric cardiac ICU arrival. Children with endotoxin assay activity levels greater than 0.6 (vs all the others) showed a significantly higher median (interquartile) number of ventilation days: 8 (2-39) versus 1.5 (1-3 (p = 0.02). CONCLUSIONS: This exploratory study showed that endotoxin assay activity levels in infants undergoing cardiopulmonary bypass are frequently above 0.4 and peak 24-48 hours after surgery and appear to be associated with perioperative impaired organ perfusion. Endotoxin assay activity is not useful to predict Gram-negative infections.

Modes of Death in a Pediatric Cardiac ICU.

OBJECTIVE: To determine epidemiology and proximate causes of death in a pediatric cardiac ICU in Southern Europe. DESIGN: Retrospective chart review. SETTING: Single-center institution. PATIENTS: We concurrently identified 57 consecutive patients who died prior to discharge from the cardiac ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over the study period, there were 57 deaths for a combined mortality rate of 2.4%. Four patients (7%) were declared brain dead, 25 patients (43.8%) died after a failed resuscitation attempt, and 28 patients (49.1%) died after withholding or withdrawal of life-sustaining treatment. Cardiorespiratory failure was the most frequent proximate cause of death (39, 68.4%) followed by brain injury (14, 24.6%) and septic shock (4, 7%). Older age at admission, presence of mechanical ventilation and/or device-dependent nutrition support, patients on a left-ventricular assist device and longer cardiac ICU stay were more likely to have life support withheld or withdrawn. CONCLUSIONS: Almost half of the deaths in the cardiac ICU are predictable, and they are anticipated by the decision to limit life-sustaining treatments. Brain injuries play a direct role in the death of 25% of patients who die in the cardiac ICU. Patients with left-ventricular assist device are associated with withdrawal of treatment.

Furosemide versus ethacrynic acid in pediatric patients undergoing cardiac surgery: a randomized controlled trial.

INTRODUCTION: Clinical effects of furosemide (F) and ethacrynic acid (EA) continuous infusion on urine output (UO), fluid balance, and renal, cardiac, respiratory, and metabolic function were compared in infants undergoing surgery for congenital heart diseases. METHODS: A prospective randomized double-blinded study was conducted. Patients received 0.2 mg/kg/h (up to 0.8 mg/kg/h) of either F or EA. RESULTS: In total, 38 patients were enrolled in the F group, and 36, in the EA group. No adverse reactions were recorded. UO at postoperative day (POD) 0 was significantly higher in the EA group, 6.9 (3.3) ml/kg/h, compared with the F group, 4.6 (2.3) ml/kg/h (P = 0.002) but tended to be similar in the two groups thereafter. Mean administered F dose was 0.33 (0.19) mg/kg/h compared with 0.22 (0.13) mg/kg/h of EA (P < 0.0001). Fluid balance was significantly more negative in the EA group at postoperative day 0: -43 (54) ml/kg/h versus -17 (32) ml/kg/h in the F group (P = 0.01). Serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels and incidence of acute kidney injury did not show significant differences between groups. Metabolic alkalosis occurred frequently (about 70% of cases) in both groups, but mean bicarbonate level was higher in the EA group: 27.8 (1.5) M in the F group versus 29.1 (2) mM in the EA group (P = 0.006). Mean cardiac index (CI) values were 2.6 (0.1) L/min/m(2) in the F group compared with 2.98 (0.09) L/min/m(2) in the EA group (P = 0.0081). Length of mechanical ventilation was shorter in the EA group, 5.5 (8.8) days compared with the F group, 6.7 (5.9) (P = 0.06). Length of Pediatric Cardiac Intensive Care Unit (PCICU) admission was shorter in the EA group: 14 (19) days compared with 16 (15) in the F group (P = 0.046). CONCLUSIONS: In cardiac surgery infants, EA produced more UO compared with F on POD0. Generally, a smaller EA dose is required to achieve similar UO than F. EA and F were safe in terms of renal function, but EA caused a more-intense metabolic alkalosis. EA patients achieved better CI, and shorter mechanical ventilation and PCICU admission time. TRIAL REGISTRATION: Clinicaltrials.gov NCT01628731. Registered 24 June 2012.

Impact of Heparin- or Nonheparin-Coated Circuits on Platelet Function in Pediatric Cardiac Surgery.

BACKGROUND: Extracorporeal circuit coating has been shown to improve coagulation derangements during pediatric cardiopulmonary bypass (CPB). This study compared platelet function and hemostasis activation in pediatric cardiac surgery conducted with nonheparin coating (Balance; Medtronic, Minneapolis, MN) versus heparin-based coating (Carmeda; Medtronic) circuits. METHODS: A prospective, randomized, double-center trial was conducted in children older than 1 month undergoing congenital heart disease treatment. Blood samples were collected at baseline (T0), 15 minutes after the start of CPB (T1), and 15 minutes (T2) and 1 hour after the conclusion of CPB (T3). The primary end point of the study was to detect potential differences in ß-thromboglobulin levels between the two groups at T2. Other coagulation and platelet function indicators were analyzed as secondary end points. RESULTS: The concentration of ß-thromboglobulin increased significantly at T2 in both groups. However, there was no significant difference between the groups across all time points. There was no difference in the secondary end points between the groups. CONCLUSIONS: The two circuits showed similar biological effects on platelet function and coagulation. This observation may be useful in optimizing the conduct of CPB and in rationalizing its cost for the treatment of congenital heart disease.

Use of low-dose dexmedetomidine in combination with opioids and midazolam in pediatric cardiac surgical patients: randomized controlled trial.

BACKGROUND: Dexmedetomidine is a selective agonist of α2 receptors that induces hypnotic, sedative and mild analgesic effect. The aim of our study was to test the effects of dexmedetomidine in combination with opioids and benzodiazepines compared to benzodiazepine-opioids alone. METHODS: A randomized controlled trial was conducted. Patients (children >30 days and <24 months undergoing correction of complex congenital heart diseases [CHD]) were randomized to receive 0.5 mcg/kg/h dexmedetomidine in addition to half dose of opioids and benzodiazepines (D-CASES) or standard dose opioids and benzodiazepines (CONTROLs). PRIMARY OUTCOME: to compare the duration of mechanical ventilation (MV) in D-CASEs and CONTROLs. SECONDARY OUTCOMES: 1) the degree of sedation; 2) the onset of withdrawal symptoms; 3) the occurrence bradycardia and hypotension. RESULTS: Overall, 48 patients, 26 in CONTROLs group and 22 in D-CASEs group were ultimately included in the analysis after enrollment. The median duration of MV was 33.5 (16.7-75) hours in CONTROLs and 41.5 (23.7-71.2) hours in D-CASEs (P=0.51). Dexmedetomidine did not affect COMFORT and FLACC scales but it reduced the SOS scale in 15 D-CASEs vs. 11 CONTROLs (P=0.001). The incidence of bradycardia and hypotension and vasoactive support did not show significant differences in the two groups. CONCLUSIONS: Low dose of dexmedetomidine in combination with morphine and midazolam was safe in a high-risk cohort of CHD children after cardiac surgery and reduced the onset of withdrawal symptoms. However, it did not decrease MV time and the total amount of other sedative and analgesic drugs required in the post-operative period.

Parenteral Nutrition Is One of the Most Significant Risk Factors for Nosocomial Infections in a Pediatric Cardiac Intensive Care Unit.

BACKGROUND: Nosocomial infections (NIs) are associated with significant morbidity and mortality and increased healthcare costs. We aimed to assess the NI epidemiology and associated risk factors in a pediatric cardiac intensive care unit (PCICU). MATERIALS AND METHODS: Prospective observational study on 1106 patients admitted to a PCICU from January 1, 2012, to October 31, 2013. NIs were defined and recorded weekly by a multidisciplinary team. Independent risk factors for NIs were assessed by logistic regression analysis in the overall cohort, in cardiac surgical patients, and in those who had cardiopulmonary bypass (CPB). RESULTS: Ninety-two patients (8.3%) had NIs. Overall mortality was 2% but 8.3% in children with NIs ( P < .001). The most frequent NIs were pneumonia (19.6%), bacteremia of unknown origin (16.3%), and catheter-associated bloodstream infection (14.1%) caused mainly by Staphylococcus aureus and Pseudomonas aeruginosa. In the overall cohort, independent risk factors for NIs were number of days of parenteral nutrition (PN), days of invasive and noninvasive ventilation, ward before PCICU admission, and days of PCICU stay; in the cardiac surgical patients, the risk factors were days of PN and days of invasive and noninvasive ventilation; in children who had undergone CPB, the risk factors for NIs were days of PN, delayed sternal closure, reintervention, length of CPB, younger age, and days of invasive ventilation. CONCLUSION: Mortality was significantly higher in patients with NIs. The use of PN was one of the most significant predictors for NIs in the overall cohort of PCICU patients, cardiac surgical patients, and those who required CPB.

High levels of free haemoglobin in neonates and infants undergoing surgery on cardiopulmonary bypass.

OBJECTIVES: Haemolysis is known to occur during surgery on cardiopulmonary bypass (CPB) and to be responsible for kidney injury. The aim of this study was to assess, in a cohort of infants, the reference levels of free haemoglobin (fHb) and their change over time postoperatively; the predicting variables of haemolysis in the intraoperative phase; and the association between fHb and renal function. METHODS: A retrospective analysis in infants undergoing surgery on CPB was conducted. Children with preoperative renal dysfunction and need for extracorporeal membrane oxygenation support were excluded. fHb was sampled before and after CPB and on the first 2 postoperative days (POD). RESULTS: Twenty-two patients with a median (interquartile) age of 111 (63-184) days and Aristotle score of 8 (6.4-9) were enrolled. fHb had a baseline value of 29 (24-41) mg/dl, peaked to 75 (65-109) mg/dl at CPB weaning and returned to 35 (30-55) mg/dl on POD 2 (P <0.0001). The median normalized index of haemolysis was 0.15 (0.09-0.19) g of fHb per 100 l of pumped blood. A multivariable regression model showed that, at CPB weaning, fHb levels were independently associated with left atrial venting flow (P = 0.02), and that CPB time remained the only independent variable (P = 0.034), when left atrial venting was excluded from the analysis. Acute kidney injury (AKI) occurred in 10 patients (45%). fHb levels in the 48 post-CPB hours were not significantly different between AKI and non-AKI patients: However, a significant correlation was present between creatinine on POD1 and CPBw-fHb (r = 0.48; P = 0.045); and between cystatin C on POD1 and CPBw-fHb (r = 0.58; P = 0.02). CONCLUSIONS: A high rate of fHb is released during paediatric surgery with CPB in infants. fHb mainly depends on the left atrial venting flow rate and CPB duration. However, such peaks of fHb levels were not associated with renal dysfunction.