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.

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.

Veno-arterial CO2 difference and cardiac index in children after cardiac surgery.

Veno-arterial CO2 difference has been considered as a marker of low cardiac output. This study aimed to evaluate the correlation between veno-arterial CO2 difference and cardiac index estimated by MostCareTM in children after cardiac surgery and its association with other indirect perfusion parameters and the complex clinical course (vasoactive inotropic score above 15 or length of stay above 5 days).Data from 40 patients and 127 arterial and venous CO2 measurements for gap calculation taken 0-5 days postoperatively were available. The median (range) veno-arterial CO2 difference value was 9 (1-25 mmHg). The correlation between veno-arterial CO2 difference and cardiac index was not significant (r: -0.16, p = 0.08). However, there was a significant correlation between veno-arterial CO2 difference and vasoactive inotropic score (r: 0.21, p = 0.02), systolic arterial pressure (r: -0.43, p = 0.0001), dP/dtMAX (r: 0.26, p = 0.004), and arterio-venous O2 difference (r: 0.63, p = 0.0001). Systolic arterial pressure (OR 0.95, 95% CI 0.90-0.99), dP/dtMAX (OR 0.00, 95% CI 0.00-0.06), lactates (OR 1.87, 95% CI 1.21-3.31), and veno-arterial CO2 difference (OR 1.13, 95% CI 1.01-1.35) showed a significant univariate association with the complex clinical course. In conclusion, veno-arterial CO2 difference did not correlate with cardiac index estimated by MostCareTM in our cohort of post-cardiosurgical children, but it identified patients with the complex clinical course, especially when combined with other direct and indirect variables of perfusion.

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.

Pressure recording analytical method and bioreactance for stroke volume index monitoring during pediatric cardiac surgery.

BACKGROUND: It is currently uncertain which hemodynamic monitoring device reliably measures stroke volume and tracks cardiac output changes in pediatric cardiac surgery patients. OBJECTIVE: To evaluate the difference between stroke volume index (SVI) measured by pressure recording analytical method (PRAM) and bioreactance and their ability to track changes after a therapeutic intervention. METHODS: A single-center prospective observational cohort study in children undergoing cardiac surgery with cardiopulmonary bypass (CPB) was conducted. Twenty children below 20 kg with median (interquartile range) weight of 5.3 kg (4.1-7.8) and age of 6 months (3-20) were enrolled. Data were collected after anesthesia induction, at the end of CPB, before fluid administration and after fluid administration. Overall, median-IQR PRAM SVI values (23 ml·m(-2), 19-27) were significantly higher than bioreactance SVI (15 ml·m(-2), 12-25, P = 0.0001). Correlation (r(2) ) between the two methods was 0.15 (P = 0.0003). The mean difference between the measurements (bias) was 5.7 ml·m(-2) with a standard deviation of 9.6 (95% limits of agreement ranged from -13 to 24 ml·m(-2)). Percentage error was 91.7%. Baseline SVI appeared to be similar, but PRAM SVI was systematically greater than bioreactance thereafter, with the highest gap after the fluid loading phase: 13 (12-18) ml·m(-2) vs. 23 (19-25) ml·m(-2), respectively, P = 0.0013. A multivariable regression model showed that a significant independent inverse correlation with patients' body weight predicted the CI difference between the two methods after fluid challenge (ß coefficient -0.12, P = 0.013). CONCLUSIONS: Pressure recording analytical method and bioreactance provided similar SVI estimation at stable hemodynamic conditions, while bioreactance SVI values appeared significantly lower than PRAM at the end of CPB and after fluid replacement.

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.

The Prevalence of Carbapenemase-Producing Microorganisms and Use of Novel Cephalosporins for the Treatment of Severe Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria in a Pediatric Cardiac Intensive Care Unit.

BACKGROUND: The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI). METHODS: All patients admitted to the cardiac ICU of the Bambino Gesù Children's Hospital in Rome during the 2016-2022 period with an invasive infection caused by a CRO were enrolled. RESULTS: The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission (p = 0.04). CONCLUSION: The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.

Whole blood assessment of neutrophil gelatinase-associated lipocalin versus pediatricRIFLE for acute kidney injury diagnosis and prognosis after pediatric cardiac surgery: cross-sectional study*.

OBJECTIVE: To assess the ability of a single whole blood neutrophil gelatinase-associated lipocalin measurement in predicting acute kidney injury occurrence, its severity, and the need for postoperative renal replacement therapy after pediatric cardiac surgery. DESIGN: Single-center prospective cross-sectional study. SETTING: Tertiary care pediatric cardiac intensive care unit. PATIENTS: Consecutive children <1 yr old with congenital heart diseases undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Neutrophil gelatinase-associated lipocalin levels were measured after pediatric cardiac intensive care unit admission. Pediatric score indicating level of renal damage by Risk, Injury, Failure, Loss of function and End-stage kidney disease (pRIFLE) was used as the reference method. Acute kidney injury was diagnosed in 90 (56%) of the 160 enrolled patients. The number of abnormal neutrophil gelatinase-associated lipocalin samples (above the cutoff level of 150 ng/mL) was 12 over 90 (13%) in acute kidney injury population and 6 over 70 in non-acute kidney injury patients (8%) (odds ratio 1.6; 95% confidence interval 0.6-4.7; p = .31). Sensitivity of neutrophil gelatinase-associated lipocalin for acute kidney injury detection was 0.13 and specificity 0.91. The number of patients with abnormal neutrophil gelatinase-associated lipocalin samples was not significantly different within pediatric score indicating level of renal damage by pRIFLE (p = .69); furthermore, we found abnormal neutrophil gelatinase-associated lipocalin levels in 4 (30%) over 13 renal replacement therapy patients and in 14 (10%) over 133 children without renal replacement therapy need (odds ratio 4.2; 95% confidence interval 1.2-10.2; p = .02). Mean cross-clamp time (p = .28), inotropic score (p = .19), surgical risk score (p = .3), mean length of mechanical ventilation (p = .48), and pediatric cardiac intensive care unit stay (p = .57) did not significantly differ between children with abnormal and normal neutrophil gelatinase-associated lipocalin values. CONCLUSIONS: Neutrophil gelatinase-associated lipocalin measured at pediatric cardiac intensive care unit arrival does not accurately predict acute kidney injury diagnosis, according to pediatric score indicating level of renal damage by pRIFLE classification. In these patients, neutrophil gelatinase-associated lipocalin might be helpful for renal replacement therapy prediction.

Neutrophil gelatinase-associated lipocalin levels during extracorporeal membrane oxygenation in critically ill children with congenital heart disease: preliminary experience.

OBJECTIVE: To evaluate diagnostic and prognostic significance of neutrophil gelatinase-associated lipocalin during extracorporeal membrane oxygenation in children with congenital heart disease. DESIGN: Prospective observational study. SETTING: Pediatric cardiac intensive care unit. PATIENTS: Ten pediatric patients with congenital heart disease requiring venoarterial extracorporeal membrane oxygenation for postoperative cardiorespiratory support were prospectively enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five patients were successfully weaned from extracorporeal membrane oxygenation and survived to intensive care unit discharge; five children died during extracorporeal therapy or within 12 hrs from extracorporeal membrane oxygenation stop. Continuous renal replacement therapy after extracorporeal membrane oxygenation start was indicated for three patients. When patients on continuous venovenous hemofiltration were compared with patients not on continuous venovenous hemofiltration, diuretic administration was lower (1.5 vs. 10 mg/kg/day), extracorporeal membrane oxygenation duration was longer (7 [range, 6-14]) vs. 4 [range, 3-8] days), and survival decreased from 60% (four of seven) to 33% (one of three). Neutrophil gelatinase-associated lipocalin levels were higher at the first extracorporeal membrane oxygenation day in patients who underwent continuous venovenous hemofiltration, 285 (range, 181-513) vs. 130 (range, 81-277) ng/mL, in patients who did not undergo continuous venovenous hemofiltration (p = .045). Neutrophil gelatinase-associated lipocalin levels remained higher among patients on continuous venovenous hemofiltration than others throughout the examined extracorporeal membrane oxygenation period (p = .0007), whereas creatinine levels tended to be equivalent between the two groups (p = .38). However, a trend toward increasing neutrophil gelatinase-associated lipocalin levels was noticed also in patients not on continuous venovenous hemofiltration. CONCLUSIONS: Neutrophil gelatinase-associated lipocalin levels at the first extracorporeal membrane oxygenation day may have predictive value for continuous venovenous hemofiltration. During the course of extracorporeal membrane oxygenation support, creatinine levels were normalized in patients with acute kidney injury undergoing continuous venovenous hemofiltration; in these patients, neutrophil gelatinase-associated lipocalin levels may provide further information on kidney injury.

High-dose fenoldopam reduces postoperative neutrophil gelatinase-associated lipocaline and cystatin C levels in pediatric cardiac surgery.

INTRODUCTION: The aim of the study was to evaluate the effects of high-dose fenoldopam, a selective dopamine-1 receptor, on renal function and organ perfusion during cardiopulmonary bypass (CPB) in infants with congenital heart disease (CHD). METHODS: A prospective single-center randomized double-blind controlled trial was conducted in a pediatric cardiac surgery department. We randomized infants younger than 1 year with CHD and biventricular anatomy (with exclusion of isolated ventricular and atrial septal defect) to receive blindly a continuous infusion of fenoldopam at 1 µg/kg/min or placebo during CPB. Perioperative urinary and plasma levels of neutrophil gelatinase-associated lipocaline (NGAL), cystatin C (CysC), and creatinine were measured to assess renal injury after CPB. RESULTS: We enrolled 80 patients: 40 received fenoldopam (group F) during CPB, and 40 received placebo (group P). A significant increase of urinary NGAL and CysC levels from baseline to intensive care unit (ICU) admission followed by restoration of normal values after 12 hours was observed in both groups. However, urinary NGAL and CysC values were significantly reduced at the end of surgery and 12 hours after ICU admission (uNGAL only) in group F compared with group P (P = 0.025 and 0.039, respectively). Plasma NGAL and CysC tended to increase from baseline to ICU admission in both groups, but they were not significantly different between the two groups. No differences were observed on urinary and plasma creatinine levels and on urine output between the two groups. Acute kidney injury (AKI) incidence in the postoperative period, as indicated by pRIFLE classification (pediatric score indicating Risk, Injury, Failure, Loss of function, and End-stage kidney disease level of renal damage) was 50% in group F and 72% in group P (P = 0.08; odds ratio (OR), 0.38; 95% confidence interval (CI), 0.14 to 1.02). A significant reduction in diuretics (furosemide) and vasodilators (phentolamine) administration was observed in group F (P = 0.0085; OR, 0.22; 95% CI, 0.07 to 0.7). CONCLUSIONS: The treatment with high-dose fenoldopam during CPB in pediatric patients undergoing cardiac surgery for CHD with biventricular anatomy significantly decreased urinary levels of NGAL and CysC and reduced the use of diuretics and vasodilators during CPB. TRIAL REGISTRATION: Clinical Trial.Gov NCT00982527.

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.

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.

Cefoxitin Prophylaxis During Pediatric Cardiac Surgery: Retrospective Exploration of Postoperative Trough Levels.

BACKGROUND: This study aimed to explore inter-individual variability of cefoxitin trough levels, predictors of serum cefoxitin concentration and the probability of target attainment of drug levels above 4 mg/L after pediatric cardiac surgery. METHODS: Retrospective study on children scheduled for elective cardiac surgery and having cefoxitin trough levels available up to 24 hours postsurgery. RESULTS: Overall, 68 children (9 neonates, 34 infants, 15 children below or equal to 10 years old and 10 patients above this age) were included. Of these, 16 surgeries were performed off cardiopulmonary bypass and 52 were performed on cardiopulmonary bypass. The free cefoxitin concentrations showed a median (interquartile range) concentration of 1.7 (0.6-4.2) mg/L. The range of cefoxitin concentrations showed a 150-fold and 340-fold variability at cardiac intensive care unit admission and after 24 hours, respectively. The pharmacodynamics (PD) targets of free cefoxitin at 100% of the dosing interval, considering Eucast breakpoints for Methicillin Sensitive Staphylococcus Aureus (4 mg/L) and E.Coli (8 mg/L), were obtained in 28% and 16% of patients, respectively. Patient weight (odds ratio, 0.7; 95% confidence interval, 0.62-0.92; P = 0.006) and serum creatinine concentrations (odds ratio, 25; 95% confidence interval, 18-36; P = 0.004) showed a significant relationship with the PD targets. CONCLUSIONS: Cefoxitin trough concentrations vary significantly in the first 24 hours after pediatric cardiac surgery. Both serum creatinine and body weight showed independent associations with cefoxitin concentration. The PD target was not obtained in the vast majority of the explored population, regardless of the target bacteria.

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.

Endotoxin Activity in Neonates Undergoing Cardiac Surgery: Cohort Study.

BACKGROUND: Endotoxemia in pediatric cardiac surgical patients is poorly understood. The endotoxin activity assay (EAA) levels were examined in neonates undergoing cardiac surgery in order to assess their reference levels and their association with other pre-, intra-, and postoperative risk factors for gut hypoperfusion. We finally observed if refeeding was associated with modification of endotoxin levels. METHODS: In a prospective cohort study, neonates undergoing surgery for correction or palliation were enrolled. Preterm birth, weight below 1.5 kg, the need for extracorporeal membrane oxygenation, and urgent surgery were exclusion criteria. RESULTS: Among the 26 enrolled neonates, 12 underwent on-pump and 14 off-pump surgery, 22 received a preoperative infusion of prostaglandin E2. Overall, 11 patients were surgically corrected and 15 received a palliation. Endotoxin activity assay baseline levels were inversely correlated with age at surgery ( r = -.50, P = .006) and they increased to postoperative day2 ( P = .002). On-pump versus off-pump surgery ( P =.36) and surgical palliation with a Blalock-Taussig shunt versus correction ( P = .45) did not predict increase in EAA levels. Aortic clamping for coarctation repair was associated with the lowest levels ( P = .04). Systolic, mean, and diastolic pressures were associated with EAA levels ( r = -.55, P = .01; r = -.45, P = .02; r = -.37, P = .04, respectively). Endotoxin activity assay levels after refeeding were similar to baseline levels. Patients with abdominal distension and feeding intolerance showed higher median peak EAA levels (0.7, 0.66-1.11) than asymptomatic patients (0.53, 0.35-0.64; P = .01). CONCLUSIONS: Endotoxin activity assay levels increase after elective neonatal surgery and are not modified by refeeding. High postoperative levels may predict feeding intolerance.

Light sedation with dexmedetomidine: a practical approach for the intensivist in different ICU patients.

Light sedation, corresponding to a Richmond Agitation-Sedation Scale between 0 and -1 is a priority of modern critical care practice. Dexmedetomidine, a highly selective, central, α2-adrenoceptor agonist, is increasingly administered in the intensive care units (ICUs) as an effective drug to induce light sedation, analgesia and a quasi-physiological sleep in critically ill patients. Although in general dexmedetomidine is well tolerated, side effects as bradycardia, hypertension, and hypotension may occur. Although a general dosing range is suggested, different ICU patients may require different and highly precise titration that may significantly vary due to neurological status, cardio-respiratory function, base-line blood pressure, heart rate, liver efficiency, age and co-administration of other sedatives. This review analyzes the use of dexmedetomidine in different settings including pediatric, adult, medical and surgical patients starting with some considerations on delirium prevention and sleep quality in critically ill patients and how dexmedetomidine may contribute to these crucial aspects. Dexmedetomidine use in specific sub-populations with unique characteristics will be detailed, with a special attention to a safe use.

Cardiac index assessment by the pressure recording analytical method in infants after paediatric cardiac surgery: a pilot retrospective study.

OBJECTIVES: Our aim was to verify whether the cardiac index (CI) estimated by the pressure recoding analytical method (PRAM) was associated with clinical metabolic indexes of tissue perfusion and mechanical ventilation duration in paediatric patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) for congenital heart disease and whether it could therefore be considered a clinically reliable monitoring method. METHODS: A retrospective study was conducted in a paediatric cardiac intensive care unit (PCICU), applying PRAM, a minimally invasive advanced haemodynamic monitoring system (MostCare®, Vygon, Vytech), for the first 24 postoperative hours. Haemodynamic and clinical average values were analysed as time-weighted average values at four postoperative time points (during the first 2 h from PCICU admission, from the 3rd to the 6th, from the 7th to the 12th and from the 13th to the 24th postoperative hours) and correlated with respective variables recorded and averaged at the same time points. RESULTS: Forty consecutive patients were enrolled. Median (interquartile range) age, CPB time and Aristotle score were 85 (47-200) days, 157 (112-185) minutes and 8.9 (7.5-10), respectively. CI values at the four time points were 2.89 (2.67-3.19), 2.94 (2.60-3.17), 2.84 (2.64-3.26) and 2.93 (2.58-3.46) l/min/m2, respectively. CI values correlated with lactate levels (r: -0.2; P = 0.01), systolic pressure (r: 0.34, P = 0.0001), heart rate (r: -0.4; P = 0.0001), vasoactive inotropic score (r: -0.3; P = 0.0001) and diuretic dose (r: -0.2; P = 0.01). In patients with low cardiac output syndrome (diagnosed according to clinical metabolic indexes), CI values estimated by PRAM were significantly lower than those of patients without signs of low cardiac output syndrome (P = 0.0001): 3.0 vs 2.8 (95% CI of difference -0.05 to 0.67), 3.1 vs 2.7 (95% CI of difference 0.13-0.85), 3.2 vs 2.7 (95% CI of difference 0.11-0.83) and 3.2 vs 2.7 (95% CI of difference 0.08-0.81) l/min/m2, respectively. Patients with a CI equal to or above 3 l/min/m2, compared with others, showed a significantly lower increase in creatinine levels from PCICU arrival to postoperative day 1: 0.07 (-0.1 to 0.2) vs 0.21 (0.05-0.3) mg/dl (P = 0.0016). Prediction of mechanical ventilation duration was independently associated only with CI (b: -3.4; r: -0.39; P = 0.04) in a multivariable model after adjustment for Aristotle score, vasoactive inotrope score, cross-clamp time, creatinine levels at PCICU admission and patient's age. CONCLUSIONS: CI estimated by PRAM after paediatric cardiac surgery was reliably associated with clinical indicators of tissue perfusion, with vasoactive and diuretic drug requirements, and predicted longer mechanical ventilation duration.

Ketamine: new indications for an old drug.

Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor for glutamate, though its effects are mediated by interaction with many others receptors. It has been introduced in clinical use since 1960's but today it is not largely employed as a general anaesthetic for its undesired psychic effects (emergence reactions) occurring in approximately 12% of patients. In the last decade, there has been a renewed interest in the use of subanaesthetic doses of ketamine for the treatment of acute and chronic pain. In the late 1990's, multiple prospective, randomised, controlled study has shown the efficacy of low dose of ketamine for postoperative pain relief, for analgesia during regional or local anaesthesia, and for opioid-sparing effect. At present, non-definitive conclusion can be drawn. More data are needed to define the possible long term effects and the clinical goal of ketamine use.