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.

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.

Clinical Factors Associated with Dose of Loop Diuretics After Pediatric Cardiac Surgery: Post Hoc Analysis.

A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH.

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.

Multisite Near Infrared Spectroscopy During Cardiopulmonary Bypass in Pediatric Patients.

Multisite near infrared spectroscopy (NIRS) monitoring during pediatric cardiopulmonary bypass (CPB) has not been extensively validated. Although it might be rational to explore regional tissue saturation at different body sites (namely brain, kidney, upper body, lower body), conflicting results are currently provided by experience in children. The aim of our study was to evaluate absolute values of multisite NIRS saturation during CPB in a cohort of infants undergoing pediatric cardiac surgery to describe average differences between cerebral, renal, upper body (arm), and lower body (thigh) regional saturation. Furthermore, the correlation between cerebral NIRS and cardiac index (CI) at CPB weaning was evaluated. Twenty-five infants were enrolled: their median weight, age, and body surface area were 3.9 (3.3-6) kg, 111 (47-203) days, and 0.24 (0.22-0.33) m(2) , respectively. Median Aristotle score was 8 (6-10), and vasoactive inotropic score at CPB weaning was 16 (14-25). A total of 17 430 data points were recorded by each sensor: two-way ANOVA showed that time (P < 0.0001) and site (P = 0.0001) significantly affected variations of NIRS values: however, if cerebral NIRS values are excluded, sensor site is no more significant (P = 0.184 in the no circulatory arrest [noCA] group and P = 0.42 in the circulatory arrest [CA] group). Analysis of NIRS saturation changes over time showed that, at all sites, average NIRS values increased after CPB start, even if the increase of cerebral saturation was less intense than other sites (P < 0.0001). Detailed analysis of interaction between site of NIRS measurement and time point showed that cerebral NIRS (ranging from 65 to 75%) was always significantly lower than that of other channels (P < 0.0001) that tended to be in the range of oversaturation (80-90%), especially during the CPB phase. Average cerebral NIRS values of patients who did not undergo circulatory arrest (CA) during CPB, 10 min after CPB weaning, were associated with average CI values with a significant correlation (r = 0.7, P = 0.003). In conclusion, during CPB, cerebral NIRS values are expected to remain constantly lower than somatic sensors, which instead tend to show similar elevated saturations, regardless of their position. Based on these results, positioning of noncerebral NIRS sensors during CPB without CA may be questioned.

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.

Steal induction in preschool children: is melatonin as good as clonidine? A prospective, randomized study.

OBJECTIVES/AIMS: To investigate whether melatonin would be an alternative drug to clonidine for performance of steal induction. BACKGROUND: Distress during induction might have a negative impact on postoperative behavior. A steal induction is a technique for smooth anesthesia induction, and clonidine has been the primary agent for this purpose. There are conflicting results regarding the efficacy of melatonin for premedication, but its sleep inducing properties have been shown in children. METHODS: Pediatric patients ASA I and II were randomly assigned to receive either melatonin 0.3 mg·kg(-1) or clonidine 4 µg·kg(-1) orally. Primary outcome was the percentage of successful steal induction, while secondary outcomes were onset of sleep, overall quality of mask induction, and adverse events at emergence from anesthesia. RESULTS: A total of 87 patients were included for analysis with a median age of 33 months (range, 12-71) and median weight of 14 kg (range, 8-26). A successful steal induction was performed in 88.4% of group C and 75% of group M (P > 0.05). Onset of sleep in these patients occurred after a median time of 45 min (range 10-60) in group C and 35 min (range 15-60) in group M (P > 0.05). Children not falling asleep after melatonin received the premedication at a significantly earlier time point compared to those falling asleep (P = 0.001). CONCLUSIONS: Melatonin was effective for steal induction in 75% of children compared to 88% of children who had clonidine. Melatonin resulted less effective when administered early in the morning.

Effects of levosimendan on ventriculo-arterial coupling and cardiac efficiency in paediatric patients with single-ventricle physiology after surgical palliation: retrospective study.

OBJECTIVES: The use of levosimendan for paediatric patients with low cardiac output after congenital heart surgery has been recently described. We sought to evaluate ventriculo-arterial coupling (VAC) and other ventricular energetic parameters before and after 72 h from levosimendan start in infants with single-ventricle physiology and cardiac failure after palliation with Norwood or hybrid procedures. METHODS: In this single-centre retrospective study, 9 consecutive patients affected by hypoplastic left heart syndrome-like anatomy were retrospectively analysed. Systolic elastance, diastolic elastance, arterial elastance, VAC and cardiac mechanical efficiency were calculated by measuring, through 2-dimensional echocardiography, end-systolic volume and end-diastolic volume and by recording mean arterial pressure and central venous pressure. RESULTS: The median (range) weight and age were 2.8 (2.3-6) kg and 16.5 (6-116) days, respectively. After 72 h from levosimendan start, end-systolic volume significantly decreased (-1 ml, -3.2 to -0.1, P = 0.007), whereas mean arterial pressure and end-diastolic volume remained stable. Heart rate showed a significant decrease (-28 beats/min, -41 to 22, P = 0.008). Systolic elastance (2.9 mmHg/ml, 0.4-5.4, P = 0.008), arterial elastance (-5.9, -24 to -0.5, P = 0.038), VAC (-0.86, -1.5 to -0.16, P = 0.009) and cardiac mechanical efficiency (0.18, 0.03-0.22, P = 0.008) differences also showed significant modifications. CONCLUSIONS: In a small case series of patients with single-ventricle physiology, levosimendan showed to improve contractility and optimize VAC, with a reduction of heart rate. Monitoring of VAC and ventricular energetics can be an interesting aspect to improve the management of heart failure in infants with univentricular anatomy.

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.

Absorption pharmacokinetics of clonidine nasal drops in children.

BACKGROUND: The alpha2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children. METHODS: Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg x kg(-1) of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography-mass spectrometry. Data were calculated by a computer-aided curve-fitting program. RESULTS: Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4-0.6 ng x ml(-1) and 1.4-3.0 h, respectively. CONCLUSIONS: Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes.

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.

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.

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.

Fiberoptic monitoring of central venous oxygen saturation (PediaSat) in small children undergoing cardiac surgery: continuous is not continuous.

BACKGROUND:  Monitoring of superior vena cava saturation (ScvO 2) has become routine in the management of pediatric patients undergoing cardiac surgery. The objective of our study was to evaluate the correlation between continuous ScvO 2 by the application of a fiber-optic oximetry catheter (PediaSat) and intermittent ScvO 2 by using standard blood gas measurements. These results were compared to those obtained by cerebral near infrared spectroscopy (cNIRS). SETTING:  Tertiary pediatric cardiac intensive care unit (PCICU). METHODS AND MAIN RESULTS:  A retrospective study was conducted in consecutive patients who were monitored with a 4.5 or 5.5 F PediaSat catheter into the right internal jugular vein. An  in vivo calibration was performed once the patient was transferred to the PCICU and re-calibration took place every 24 hours thereafter. Each patient had a NIRS placed on the forehead. Saturations were collected every 4 hours until extubation. Ten patients with a median age of 2.2 (0.13-8.5) years and a weight of 12.4 (3.9-24) kg were enrolled. Median sampling time was 32 (19-44) hours: 64 pairs of PediaSat and ScVO2 saturations showed a poor correlation (r=0.62, 95% CI 44-75; p<0.0001) and Bland Altman analysis for repeated measures showed an average difference of 0.34 with a standard deviation of 7,9 and 95% limits of agreement from -15 to 16. Thirty-six pairs of cNIRS and ScVO2 saturations showed a fair correlation (r=0.79, 95% CI 0.60-0.89; p<0.0001) an average difference of -1.4 with a standard deviation of 6 and 95% limits of agreement from -13 to 10. Analysis of median percentage differences between PediaSat and ScvO2 saturation over time revealed that, although not statistically significant, the change in percentage saturation differences was clinically relevant after the 8th hour from calibration (from -100 to +100%). CONCLUSION:  PediaSat catheters showed unreliable performance in our cohort. It should be further investigated whether repeating calibrations every 8 hours may improve the accuracy of this system. CNIRS may provide similar results with a lower invasiveness.

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.

Comparative evaluation of high-flow nasal cannula and conventional oxygen therapy in paediatric cardiac surgical patients: a randomized controlled trial.

OBJECTIVES: The aim of this study was to compare high-flow nasal cannula (HFNC) and conventional O2 therapy (OT) in paediatric cardiac surgical patients; the primary objective of the study was to evaluate whether HFNC was able to improve PaCO2 elimination in the first 48 h after extubation postoperatively. METHODS: We conducted a randomized, controlled trial in pediatric cardiac surgical patients under 18 months of age. At the beginning of the weaning of ventilation, patients were randomly assigned to either of the following groups: OT or HFNC. Arterial blood samples were collected before and after extubation at the following time points: 1, 6, 12, 24 and 48 h. The primary outcome was comparison of arterial PaCO2 postextubation; secondary outcomes were PaO2 and PaO2/fractional inspired oxygen (FiO2) ratio, rate of treatment failure and need of respiratory support, rate of extubation failure, rate of atelectasis, simply to complications and the length of paediatric cardiac intensive care unit stay. RESULTS: Demographic and clinical variables were comparable in the two groups. Analysis of variance for repeated measures showed that PaCO2 was not significantly different between the HFNC and OT groups (P = 0.5), whereas PaO2 and PaO2/FiO2 were significantly improved in the HFNC group (P = 0.01 and P = 0.001). The rate of reintubation was not different in the two groups (P = 1.0), whereas the need for noninvasive respiratory support was 15% in the OT group and none in the HFNC group (P = 0.008). CONCLUSIONS: HFNC had no impact on PaCO2 values. The use of HFNC appeared to be safe and improved PaO2 in paediatric cardiac surgical patients.

Premedication in children: a comparison of oral midazolam and oral clonidine.

BACKGROUND: Oral premedication is widely used in pediatric anesthesia to reduce preoperative anxiety and ensure smooth induction. Midazolam is currently the most commonly used premedicant, but good results have also been reported with clonidine. The aim of the present study was to compare clinical effects of oral midazolam and oral clonidine. METHODS: We performed a prospective open study in 64 children who were randomly assigned to receive either oral midazolam 0.5 mg.kg (-1) (group M) or oral clonidine 4 microg.kg (-1) (group C) prior to mask induction. Drug acceptance, preoperative sedation and anxiolysis, quality of mask acceptance, recovery profile and parental satisfaction were evaluated. RESULTS: The taste of oral clonidine was judged as significantly better; 14% of children rejected oral midazolam. Onset of sedation was significantly faster after premedication with midazolam (30+/-13.1 min) than with clonidine (38.5+/-14.6 min), but level of sedation was significantly better after premedication with clonidine. Quality of mask induction was equally successful in both groups. A steal-induction was performed in 66% of patients of group C, but none in group M. We observed a trend towards an increased incidence of emergence agitation after premedication with midazolam. Parental satisfaction was significantly higher in group C. CONCLUSIONS: In this study, premedication with oral clonidine appeared to be superior to oral midazolam. Quality of mask acceptance was comparable between groups, but oral clonidine was better accepted by the child, produced more effective preoperative sedation, showed a trend towards better recovery from anesthesia and had a higher degree of parental satisfaction.

Steal-induction after clonidine premedication: a comparison of the oral and nasal route.

BACKGROUND: Clonidine premedication in children reliably provides preoperative sedation and anxiolysis, but onset of oral clonidine is known to be slow. Nasal clonidine has been shown to reach peak plasma levels within 10 min in rodents. The aim of the present study was to compare clinical effects and percentage of steal-induction after clonidine premedication by the oral and nasal route. METHODS: Forty children, aged 1-6 years, scheduled for minor infraumbilical surgery, were randomly assigned to receive either pure clonidine 4 microgxkg(-1) intranasally (group CN, n = 20) or clonidine 4 microgxkg(-1) orally in syrup (group CO, n = 20) prior to mask induction. Drug acceptance, preoperative sedation and anxiolysis, quality of mask acceptance, recovery profile and parents' satisfaction were evaluated. RESULTS: Drug acceptance was similar between groups, but quality of taste was significantly better in the oral group. There was no significant difference of preoperative anxiolysis and sedation. The onset of sedative effect was after 38.3 min for oral clonidine and 47.5 min for nasal clonidine. A steal-induction could be performed in 60% of children in each group. Emergence from anesthesia and parents' satisfaction were comparable. CONCLUSIONS: Intranasal clonidine administration has no advantage over the oral route. Clinical effects were similar with both routes; there was a trend towards a faster onset of sedation with oral clonidine. Clonidine premedication causes light sleep, which allows a steal-induction in 60% of patients.

Insertion characteristics, sealing pressure and fiberoptic positioning of CobraPLA in children.

BACKGROUND: The CobraPLA(TM) is a new supraglottic airway device designed for the use in spontaneously breathing and mechanically ventilated patients. In adults it has been found as effective as the LMA, but with better sealing qualities. The aim of the present study was to evaluate fit and sealing characteristics of CobraPLA size 1.5 and 2 in mechanically ventilated children. METHODS: Forty children, ASA I/II, aged 1-10 years, weighing 10-35 kg were scheduled for minor surgical procedures. The number of attempts for insertion and fiberoptic positioning of the CobraPLA was assessed. After muscle relaxation had been achieved, airway sealing pressure was measured by gradually increasing maximum inspiratory pressure to a maximum of 30 cm H(2)O. RESULTS: Insertion of CobraPLA was successful at the first attempt in 90% of patients. The vocal cords were visualized in 90% of patients (grade 0: 2.5%, grade 1: 7.5%, grade 2: 30%, grade 3: 15%, grade 4: 45%). Median sealing pressure was 20.0 +/- 6.0 cm H(2)O. In 21% of patients gastric insufflation was observed at a peak inspiratory pressure of 20 cm H(2)O or below. CONCLUSIONS: The CobraPLA was found to have easy insertion characteristics and good anatomical fitting in children between 10 and 35 kg. If positive pressure ventilation with CobraPLA size 1.5 and 2.0 is required, peak inspiratory pressure should be kept below the leak pressure and the abdomen closely monitored for signs of gastric insufflation.