Diagnostic Agreement Between TEG5000 and TEG6S in the Assessment of Hemostasis in Pediatric Cardiac Surgery: A Prospective Non-inferiority Study.

Thromboelastography (TEG) is a point-of-care test (POCT) used to analyze the hemostatic properties of whole blood. TEG® 5000and TEG® 6s (Haemonetics Corp, USA) measure the same parameters describing clot viscoelasticity using different methodologies. The purpose of this study was to evaluate agreement between TEG5000 and TEG6s measurements. We analyzed prospectively collected tests resulting from paired blood samples in cardiac surgery pediatric patients at one hour (T0) and 24 h (T1) postoperatively. Each citrated sample was utilized for TEG® 5000 and TEG ®6s. Six specific TEG parameters were analyzed and compared: R kaolin time (RK), R kaolin heparinase (RKH) time, K kaolin time (KK), K kaolin heparinase time KH (KKH), Maximum Amplitude kaolin (MAK), Maximal Amplitude Kaolin Heparinase (MAKH). We enrolled 30 patients. Median (interquartile range) patients' age was 206 (20-597) days. All surgical patients underwent correction except 5 who were palliated. At T0, RK and RKH showed an average (standard deviation) % bias of 15.8 (31) and 16.1 (28), respectively, with similar results at T1. A % bias of -6 (23) and - 6 [15] in MAK was found at T0 and T1, respectively. Similarly, MAKH % bias was 1.5 (22) and 7.6 (29) at T0 and T1, respectively. At both timepoints, low % biases (< ± 6%) were demonstrated in KK and KKH. All parameters showed improved coagulation from T0 to T1, but without significant interaction between type of device and time. Analysis of the entire pool of 60 paired samples showed no agreement in diagnostic performance (within the range vs. outside the range) in 12 (20%), 5 (9.8%), 1 (1.7%), 4 (7.8%), 9 (15%), and 5 (9.8%) cases for RK, RKH, MAK, MAKH, KK and KKH, respectively. We observed substantial agreement in MAK and KK in a cohort of pediatric patients undergoing uncomplicated cardiac surgery. Our findings suggest that TEG®5000 and TEG®6s are interchangeable for assessing these parameters.

Predictors of survival in paediatric mitral valve surgery: the impact of age at operation at late follow-up.

OBJECTIVES: The aim of this study was to elucidate predictors of death and reintervention after mitral valve (MV) surgery in children. METHODS: A single-centre retrospective study was performed enrolling 142 patients younger than 18 years who underwent primary index surgical mitral repair or replacement at Bambino Gesù Children's Hospital in Rome from July 1982 to April 2020. Patients with complete, transitional or partial atrioventricular septal defect and patients with single ventricle physiology were excluded. Patients were stratified according to the age group: group 1 (<1 year old), group 2 (1-5 years old) and group 3 (>5 years old). The composite primary outcome was freedom from death or transplant. The secondary outcome was freedom from redo MV surgery. RESULTS: Transplant-free survival was 89% at 5 years and 88% at 10 years. Stratified by age, group 1 had poorer outcome in comparison with other groups (log-rank test P = 0.105). Both univariate and multivariate analyses showed that age <1 year was a significant risk factor for death or transplant (P = 0.044). Age <1 year was associated with increased risk of reoperation (aHR = 3.38, P = 0.009), while the presence of genetic syndrome (aHR = 0.22) and preoperative EF% (aHR = 0.97) were protective factors for reoperation. CONCLUSIONS: The overall survival and freedom from reoperation in children undergoing MV surgery still need improvements. Younger age was a significant risk factor for death and reintervention both after repair and replacement of the MV. In particular, infants and neonates have a three-fold risk for death compared to children.

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study.

INTRODUCTION: Few data are available regarding intraoperative plasma concentrations of vancomycin administered as prophylaxis in pediatric cardiac surgery. The aims of this study were to investigate during pediatric cardiac surgery with cardiopulmonary bypass(CPB) the attainment of the area-under-the-curve of the vancomycin serum concentrations versus time over surgery to minimum inhibitory concentration ratio(AUCintra/MIC) of 400 (mg × h)/l and/or a target concentration of 15-20 mg/l. METHODS: In a prospective study, 40 patients divided into four subgroups (neonates, infants, children <10 years-old, ⩾10 years-old) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. A slow vancomycin bolus of 20 mg/kg, up to a maximum dose of 1000 mg was administered before skin incision and a further dose of 10 mg/kg (up to 500 mg) at CPB start. Vancomycin samples were collected intraoperatively at four time points. RESULTS: The median (interquartile range) age was 241.5 days (47-3898) and the median weight was 7.1 kg (3.1-37). The median AUCintra/MIC was 254.73 (165.89-508.06). In 11 patients the AUCintra/MIC target was not reached. Neonates displayed the lowest AUCintra/MIC values, and these were significantly lower than those of children ⩾10 years old (p = 0.02). Vancomycin concentrations were above the maximal target of 20 mg/l in 82.5% and 80% of patients at surgery and CPB start, respectively. At CPB and surgery end, 42.5% of patients showed vancomycin concentrations above 20 mg/l and 42.5% below 15 mg/l. Patients⩾10 years old showed the highest peak values whereas neonates were those with the lowest troughs. AUCintra/MIC correlated with age(r:0.36, p = 0.02), weight(r:0.35, p = 0.03), intraoperative protein value(r:0.40, p = 0.01), CPB priming volume/kg(r:-0.33, p = 0.04), CPB duration(r:0.36, p = 0.02) and vancomycin troughs(r:0.35, p = 0.04). CONCLUSIONS: An AUCintra/MIC ⩾400 target was not reached in one-quarter of children undergoing heart surgery. Vancomycin peaked before the start of surgery and neonates were those with the lowest troughs. Vancomycin concentrations are affected by CPB hemodilution and by patients' age and weight.

Pediatric Mechanical Circulatory Support: Pathophysiology of Pediatric Hemostasis and Available Options.

Pediatric mechanical circulatory support (MCS) is considered a strategy for heart failure management as a bridge to recovery and transplantation or as a destination therapy. The final outcome is significantly impacted by the number of complications that may occur during MCS. Children on ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are at high risk for bleeding and thrombotic complications that are managed through anticoagulation. The first detailed guideline in pediatric VADs (Edmonton Anticoagulation and Platelet Inhibition Protocol) was based on conventional antithrombotic drugs, such as unfractionated heparin (UFH) and warfarin. UFH is the first-line anticoagulant in pediatric MCS, although its profile is not considered optimal in pediatric setting. The broad variation in heparin doses among children is associated with frequent occurrence of cerebrovascular accidents, bleeding, and thrombocytopenia. Direct thrombin inhibitors (DTIs) have been utilized as alternative strategies to heparin. Since 2018, bivalirudin has become the chosen anticoagulant in the long-term therapy of patients undergoing MCS implantation, according to the most recent protocols shared in North America. This article provides a review of the non-traditional anticoagulation strategies utilized in pediatric MCS, focusing on pharmacodynamics, indications, doses, and monitoring aspects of bivalirudin. Moreover, it exposes the efforts and the collaborations among different specialized centers, which are committed to an ongoing learning in order to minimize major complications in this special pediatric population. Further prospective trials regarding DTIs in a pediatric MCS setting are necessary and in specific well-designed randomized control trials between UFH and bivalirudin. To conclude, based on the reported literature, the clinical use of the bivalirudin in pediatric MCS seems to be a value added in controlling and maybe reducing thromboembolic complications. Further research is necessary to confirm all the results provided by this literature review.

Predictors of survival in paediatric mitral valve replacement.

OBJECTIVES: The aim of this study was to identify the predictors of death and of reintervention after mitral valve replacement (MVR) in children. METHODS: A single-centre retrospective study was performed including 115 patients under the age of 18 undergoing MVR between 1982 and 2019. For all patients, the ratio of prosthetic valve size (diameter in mm) to weight (kg) at surgery was calculated and long-term result was assessed. The primary outcome was freedom from mitral valve (MV) re-replacement. The composite secondary outcome was freedom from death or transplant. RESULTS: Fifty-four patients had a previous surgical attempt to MV repair. The median age at surgery was 5.5 years (interquartile range 1.21-9.87). Death/transplant-free survival was 77 ± 4% at 5 years and 72 ± 5% at 10 years. Univariate analysis showed a size/weight ratio higher than 2 and age <2 years as significant risk factors for death or transplant. Freedom from MV re-replacement at 5 and 10 years was 90 ± 3% and 72 ± 6%, respectively. Biological prosthesis implanted at first replacement (P = 0.007) and size/weight ratio higher than 2 (P = 0.048) were predictors of reoperation. Significant upsizing (P < 0.0001) of mitral prosthesis was observed at re-replacement. CONCLUSIONS: MVR is a viable strategy in children with unrepairable MV disease. Mortality can be predicted based on size/weight ratio and age <2 years. MV re-replacement can be performed with low morbidity and mortality and a larger-size prosthesis can often be placed at the time of redo.

Long-term veno-arterial extracorporeal membrane oxygenation as a bridge to heart-lung transplant.

En bloc heart-lung transplantation still represents definitive therapy for end-stage cardiopulmonary failure. However, patients may critically decompensate while awaiting suitable donor organs and necessitate veno-arterial extracorporeal membrane oxygenation. In this article, we describe the combined use of central cannulation with the Berlin Heart EXCOR ventricular assist device cannulae and the CentriMag centrifugal pump as an extended bridge to heart-lung transplantation in three pediatric patients.

Population Pharmacokinetics of Cefoxitin Administered for Pediatric Cardiac Surgery Prophylaxis.

BACKGROUND: Available data about pharmacokinetics (PK) of antimicrobials administered as surgical prophylaxis to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) showed that drug concentrations during CPB may be supra or subtherapeutic. The aim of this study was to determine the population PK and pharmacodynamic target attainment (PTA) of cefoxitin during pediatric CPB surgery. METHODS: A prospective interventional study was conducted. Cefoxitin (40 mg/kg, up to max 1000 mg) was administered before skin incision. Blood samples were obtained in the operatory room throughout surgery. Population PK, PTA, and safety of cefoxitin were evaluated in neonates, infants, children <10 and >10 years old. RESULTS: Forty patients were enrolled. Cefoxitin levels correlated with time from bolus administration (r = -0.6, P = 0.0001) and, after 240 minutes from bolus, drug values below the target (8 mg/L) were shown. Cefoxitin concentrations were best described by a one-compartment model with first order elimination. A significant relationship was identified between body weight, age, body mass index, and serum creatinine on drug clearance and age, body weight, and body mass index on cefoxitin volume of distribution. The PTA for free drug concentration being above the minimum inhibitory concentration of 8 mg/L for at least 240 minutes was >90% in all age groups except in patients >10 years of age (PTA = 62%). CONCLUSIONS: Cefoxitin PK appears to be significantly influenced by CPB with generally reduced drug clearance. The PTA was adequately achieved in the majority of patients except in patients >10 years old or longer surgeries.

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.

Platelet-mapping assay for monitoring antiplatelet therapy during mechanical circulatory support in children: A retrospective observational study.

INTRODUCTION: The complex hemostatic changes associated with Berlin Heart (BH) implantation in children require a challenging antithrombotic treatment. The aim of this retrospective analysis was to evaluate the thromboelastography (TEG)-platelet mapping (PM) assay to monitor antiplatelet therapy in children implanted with a BH. METHODS: TEG-PM was performed in 4 BH-implanted patients receiving dipyridamole and aspirin, and 9 healthy volunteers. Patients' antiplatelet therapy was adjusted to TEG-PM results. Light transmission aggregometry (LTA) was also available for 2 of these patients. RESULTS: Between 2009 and 2014, 4 BH-implanted patients received a dual antiplatelet therapy monitored by TEG-PM. In 2 patients, 18 of 34 tracings were atypical, because the maximum amplitude due to fibrin never stabilized, which made difficult antiplatelet therapy adjustment as recommended by BH's guidelines. To overcome this difficulty, TEG-PM and LTA were next performed in parallel. However, both methods led to different decisions to adjust antiplatelet therapy in 57% of the cases. In order to better understand this atypical tracing, TEG-PM was also performed in 9 volunteers and surprisingly 3 of them had the same atypical tracing. This atypical tracing was corrected by adding apyrase, suggesting that adenosine diphosphate (ADP) participates to spontaneous platelet activation in heparinized samples. In addition, we evidenced a high variability in the responses of TEG-PM with ADP in volunteers. CONCLUSIONS: Antiplatelet therapy monitoring in BH-implanted children remains challenging, as TEG-PM is sensitive to several preanalytical and analytical conditions.

Use of Confidex to control perioperative bleeding in pediatric heart surgery: prospective cohort study.

Bleeding during and after cardiac surgery is a major issue in pediatric patients. A prospective cohort study was conducted to evaluate the effect of a commercially available prothrombin complex (Confidex) administered in cardiac surgery after weaning from cardiopulmonary bypass of infants with nonsurgical bleeding. In this study, 14 patients younger than 1 year received a Confidex bolus and were matched with 11 patients of a similar age who did not receive the drug. The preoperative coagulation profile was similar in the two groups. No side effects, including anaphylaxis or thrombotic events, were observed. The numbers of units of packed red blood cells and fresh frozen plasma administered both intra- and postoperatively were similar. The postoperative coagulation examination results and thromboelastographic parameters did not differ significantly between the two groups. However, the Confidex patients bled significantly less than the control subjects during the first 24 postoperative hours. The median volume of drained blood was 0.0 ml/kg h (range 0-1.9 ml/kg h) compared with 1.9 ml/kg h (range 1-3 ml/kg h) (p = 0.009). At least one unit of packed red blood cells in the postoperative phase was required by 2 patients (14 %) in the Confidex group and six patients (54 %) in the control group (odds ratio [OR], 0.13; 95 % confidence interval [CI], 0.02-0.9; p = 0.03). The median duration of mechanical ventilation was 3 days (range 2-4 days) in the Confidex group and 4 days (range 0-8 days) in the control group (p = 0.66). The median stay in the intensive care unit was 6 days (range 5-9 days) in the Confidex group and 7 days (range 4-12 days) in the control group (p = 0.88). The use of Confidex for infants undergoing cardiac surgery was safe and effective. It reduced postoperative bleeding and allowed fewer units of packed red blood cells to be infused in the postoperative phase without major side effects.

Cerebral NIRS as a marker of superior vena cava oxygen saturation in neonates with congenital heart disease.

OBJECTIVES: To investigate the correlation between cerebral near-infrared spectroscopy (NIRS) (rSO2c) and superior vena cava venous oxygen saturation (ScvO2) in newborn patients with congenital heart disease (CHD). BACKGROUND: NIRS is a noninvasive method to monitor hemoglobin oxygen saturation using nonpulsatile oximetry. METHODS: We retrospectively analyzed perioperative data from 100 newborn patients who underwent cardiac surgery for CHD. rSO2c, ScvO2 from 24 h before to 72 h after surgery were recorded. RESULTS: rSO2c had a fair correlation with ScvO2 (r 0.37; P <0.001). The relationship between rSO2c and ScvO2 did not change when analyzed between patients with cyanotic or acyanotic CHD. During the preoperative period, rSO2c levels overestimated ScvO2; in the first 18 postoperative hours, rSO2c underestimated ScvO2; after that period, they showed very close trends. Hypocapnia caused rSO2c to underestimate ScvO2; in normocapnic patients, rSO2c-ScvO2 average differences were close to zero; in hypercapnic neonates, rSO2c tended to overestimate ScvO2. The best performance of rSO2c as a surrogate of ScvO2 was found in the venous saturation ranges from 40% to 60% (r 0.3, P: 0.03). CONCLUSIONS: rSO2c in newborn patients with cyanotic and acyanotic CHD provides a continuous noninvasive information with a fair correlation with ScvO2%: some predictable variables (i.e., time from surgery, carbon dioxide, and venous saturation levels), should guide the operators to adjust rSO2c values in terms of ScvO2. Serial measures of ScvO2 seem recommended to tailor rSO2c information on actual venous saturation percentage.

Neurally adjusted ventilatory assist and lung transplant in a child: A case report.

OBJECTIVE: To report the successful application of neurally adjusted ventilatory assist to a child with cystic fibrosis who underwent single-lung transplantation. DESIGN: Case report. SETTING: Pediatric cardiac intensive care unit. PATIENT: A 15-yr-old male with cystic fibrosis was admitted to our pediatric cardiac intensive care unit after single-lung transplantation. The child had previously received two bowel resections at the age of 1 yr, right pneumonectomy at the age of 3 yrs, and endoscopic percutaneus gastrostomy at the age of 10 yrs. After transplant, the child failed several attempts of weaning off mechanical ventilation with pressure-support ventilation, due to infection, pneumothorax, and ventilator asynchrony that caused gastric distension and numerous episodes of nausea and vomiting. INTERVENTION: Use of neurally adjusted ventilatory assist to avoid patient-ventilator dyssynchrony and consequent gastric distension. CONCLUSIONS: The utilization of neurally adjusted ventilatory assist allowed to limit the risk of overassistance and prevent patient-ventilator asynchrony and to successfully wean the child off mechanical ventilation after single-lung transplant.

Initial single-center experience with levosimendan infusion for perioperative management of univentricular heart with ductal-dependent systemic circulation.

The aim of this study was to evaluate the safety and the efficacy of levosimendan, a novel calcium sensitizer agent, on postoperative hemodynamic and metabolic parameters of neonates affected by single ventricle anatomy. Twenty consecutive neonates scheduled for the Norwood procedure with Blalock Taussig shunt were prospectively enrolled. All patients received an infusion of levosimendan at 0.1 µg/kg/min commencing 24 hours before surgery, and the infusion was continued for 48 hours after surgery. No side effects (intolerance to the drug, hypotension, arrhythmias) were shown. A median inotropic score (IS) of 37 was necessary to maintain a mean arterial pressure between 45 and 50 mm Hg at intensive care unit (ICU) admission: IS was significantly reduced after 72 hours (P < .05). Brain natriuretic peptide values decreased significantly from 1210 to 459 pg/mL in 72 hours (P < .05). Median SvO2 increased significantly from 38% to 59% during the evaluated period (P < .05). Cerebral near-infrared spectroscopy values were close to 40% at ICU admission with a significant stable increase to 50% after 12 hours (P < .05). Median lactate level was 13 mmol/L at ICU admission but showed a trend to a rapid and significant decrease after 12 hours (P < .05). Median urine output was surprisingly elevated, always remaining between 5.2 and 6.2 mL/kg/h throughout the postoperative period. Survival rate was 85% at 30 days (17/20 patients) and 75% (15/20) at hospital discharge. Levosimendan infusion in a cohort of neonates with univentricular anatomy was safe and potentially beneficial on postoperative hemodynamic and metabolic parameters.

Fenoldopam in newborn patients undergoing cardiopulmonary bypass: controlled clinical trial.

We determined if low dose fenoldopam in neonates already receiving conventional diuretics improves urine output, fluid balance, acute kidney injury incidence (AKI) and time to extubation. A prospective controlled clinical trial in a pediatric cardiac intensive care unit on 40 neonates undergoing cardiac surgery with cardiopulmonary bypass, excluding simple ventricular septal defect and atrial septal defect. Fenoldopam was infused at a low dose of 0.1 microg/kg/min soon after anesthesia induction and infusion prolonged for 72 h in 20 patients. Twenty neonates with standardized perioperative therapy except fenoldopam administration served as controls. Demographic, hemodynamic, daily urine output, creatinine, creatinine clearance, serum and urinary sodium and potassium were recorded. Inotropic score (IS) was calculated as a surrogate for the degree of hemodynamic impairment. Low dose fenoldopam infusion did not show beneficial effects in renal function. The treatment did not significantly affect IS value, AKI incidence, fluid balance control, time to sternal closure, time to extubation and time to intensive care unit discharge. Low dose fenoldopam in neonates undergoing cardiac surgery with CPB did not produce effects on urine output, fluid balance and AKI incidence. Fenoldopam was well tolerated and did not negatively affect hemodynamics and vasopressor support.

Role of vasopressin in the treatment of anaphylactic shock in a child undergoing surgery for congenital heart disease: a case report.

INTRODUCTION: The incidence of anaphylactic reactions during anesthesia is between 1:5000 and 1:25000 and it is one of the few causes of mortality directly related to general anesthesia. The most important requirements in the treatment of this clinical condition are early diagnosis and maintenance of vital organ perfusion. Epinephrine administration is generally considered as the first line treatment of anaphylactic reactions. However, recently, new pharmacological approaches have been described in the treatment of different forms of vasoplegic shock. CASE PRESENTATION: We describe the case of a child who was undergoing surgery for ventricular septal defect, with an anaphylactic reaction to heparin that was refractory to epinephrine infusion and was effectively treated by low dose vasopressin infusion. CONCLUSION: In case of anaphylactic shock, continuous infusion of low-dose vasopressin might be considered after inadequate response to epinephrine, fluid resuscitation and corticosteroid administration.

Inotropic support and peritoneal dialysis adequacy in neonates after cardiac surgery.

We describe the impact of cardiovascular pharmacologic support on peritoneal dialysis adequacy in 20 neonates who required postoperative renal replacement therapy following cardiopulmonary bypass exposure. Peritoneal dialysis was administered for 2.5 (2) days. Peritoneal dialysis creatinine clearance was 3.4 (2.1) ml/min/1.73 m(2) and ultrafiltration rate was 9.75 (10) ml/h. Residual creatinine clearance was 31 (26) ml/min/1.73 m(2). Peritoneal dialysis creatinine clearance appeared to be a function of dialysate flow up to 100 ml/h. No correlation was present between inotropes and vasopressors infusion and peritoneal dialysis creatinine clearance/ultrafiltration rate. LDH clearance was 0.59 (0.85) ml/min/1.73 m(2) and it did not appear to have a correlation with dialysate flow. Patients in-hospital mortality was 20%, significantly higher than overall neonatal population admitted to our ICU (4.8%, P=0.02). Peritoneal dialysis in neonates allows optimal ultrafiltration rate and adequate small solute clearance, irrespective of hemodynamic status or vasopressor support.