Sarah N. Fernández

Postoperative neutrophil gelatinase-associated lipocalin predicts acute kidney injury after pediatric cardiac surgery*.

Objective: We investigated the temporal pattern and predictive value of neutrophil gelatinase–associated lipocalin for early identification of acute kidney injury in children undergoing cardiac surgery. Design: Prospective observational cohort study. Setting: One PICU in a tertiary medical center in Madrid, Spain. Patients: One hundred six children older than 15 days and younger than 16 years undergoing surgery for congenital cardiac lesions. Interventions: None. Measurements and Main Results: Urine samples were obtained before and at intervals after surgery. Acute kidney injury was defined according to pediatric Risk, Injury, Failure, Loss, and End-stage kidney disease criteria. The temporal pattern of both urine neutrophil gelatinase–associated lipocalin absolute concentration elevation and normalized to urine creatinine concentration was correlated with the development of acute kidney injury and other clinical outcomes. We evaluated the predictive ability of both urine neutrophil gelatinase–associated lipocalin and urine neutrophil gelatinase–associated lipocalin/creatinine by area under the curve, when added to a clinical predictive model. Data from 106 pediatric patients were analyzed. Acute kidney injury occurred in 42 patients (39.6%). Urine neutrophil gelatinase–associated lipocalin significantly increased in patients with acute kidney injury at 1, 3, and 15 hours postoperatively. Urine neutrophil gelatinase–associated lipocalin and urine neutrophil gelatinase–associated lipocalin/creatinine correlated with surgical variables and clinical outcomes. Acute kidney injury prediction improved when urine neutrophil gelatinase–associated lipocalin was added to a clinical model (area under the curve increased at 1 hr from 0.85 to 0.91 and at 3 hr to 0.92). Neither the urine neutrophil gelatinase–associated lipocalin nor the urine neutrophil gelatinase–associated lipocalin/creatinine values were significantly different between patients with prerenal and sustained acute kidney injury. Conclusions: Urine neutrophil gelatinase–associated lipocalin is a predictive biomarker for acute kidney injury after pediatric cardiac surgery, and it may permit earlier intervention that improves outcome of acute kidney injury. Urine neutrophil gelatinase–associated lipocalin normalized to urine creatinine improves the prediction of acute kidney injury severity but offers no advantage in acute kidney injury diagnosis.

Microcirculatory alterations during haemorrhagic shock and after resuscitation in a paediatric animal model

BACKGROUND Haemorrhagic shock is frequent in paediatric trauma patients and after cardiac surgery, especially after cardiopulmonary bypass. It has demonstrated to be related to bad outcome. OBJECTIVES To evaluate changes on microcirculatory parameters during haemorrhagic shock and resuscitation in a paediatric animal model. To determine correlation between microcirculatory parameters and other variables routinely used in the monitoring of haemorrhagic shock. METHODS Experimental study on 17 Maryland pigs. Thirty minutes after haemorrhagic shock induction by controlled bleed animals were randomly assigned to three treatment groups receiving 0.9% normal saline, 5% albumin with 3% hypertonic saline, or 5% albumin with 3% hypertonic saline plus a bolus of terlipressin. Changes on microcirculation (perfused vessel density (PVD), microvascular blood flow (MFI) and heterogeneity index (HI)) were evaluated and compared with changes on macrocirculation and tisular perfusion parameters. RESULTS Shock altered microcirculation: PVD decreased from 13.5 to 12.3 mm mm(-2) (p=0.05), MFI decreased from 2.7 to 1.9 (p<0.001) and HI increased from 0.2 to 0.5 (p<0.001). After treatment, microcirculatory parameters returned to baseline (PVD 13.6 mm mm(-2) (p<0.05), MFI 2.6 (p<0.001) and HI 0.3 (p<0.05)). Microcirculatory parameters showed moderate correlation with other parameters of tissue perfusion. There were no differences between treatments. CONCLUSIONS Haemorrhagic shock causes important microcirculatory alterations, which are reversed after treatment. Microcirculation should be assessed during haemorrhagic shock providing additional information to guide resuscitation.

Constipation in the Critically Ill Child: Frequency and Related Factors

OBJECTIVE To analyze the incidence and factors associated with constipation in critically ill children. STUDY DESIGN We performed a prospective observational study that included children admitted to the pediatric intensive care unit for more than 3 days. Constipation was defined as more than 3 days without a bowel movement. Relationships between constipation and demographic data; clinical severity score; use of mechanical ventilation, use of vasoconstrictors, sedatives, and muscle relaxants; nutritional data; electrolyte disturbances; and clinical course were analyzed. RESULTS Constipation developed in 46.7% of the 150 patients studied (mean age, 34.3 ± 7.1 months). It was most common in postoperative, older, and higher-body-weight patients, and in those with fecal continence (P < .01). Compared with patients without constipation, patients with constipation had higher severity scores and more frequently received midazolam, fentanyl, muscle relaxants, and inotropic support (P < .05). Patients with constipation also started nutrition later and with a lower volume of nutrition (P < .01). There were no between-group differences in mortality or length of pediatric intensive care unit stay. In multivariate analysis, independent factors associated with constipation were body weight (OR, 1.08; 95% CI, 1.03-1.13), Pediatric Index of Mortality 2 score (OR, 1.05; 95% CI, 1.02-1.09), admission after surgery (OR, 7.64; 95% CI, 2.56-22.81), and treatment with vasoconstrictors (OR, 10.28; 95% CI, 3.53-29.93). CONCLUSION Constipation is common in critically ill children. Body weight, Pediatric Index of Mortality 2 clinical severity score, admission after surgery, and the need for vasoconstrictor therapy are major independent risk factors associated with constipation.

Adrenaline, terlipressin, and corticoids versus adrenaline in the treatment of experimental pediatric asphyxial cardiac arrest.

Objective: To analyze if treatment with adrenaline (epinephrine) plus terlipressin plus corticoids achieves higher return of spontaneous circulation than adrenaline in an experimental infant animal model of asphyxial cardiac arrest. Design: Prospective randomized animal study. Setting: Experimental department in a University Hospital. Subjects: Forty-nine piglets were studied. Interventions: Cardiac arrest was induced by at least 10 minutes of removal of mechanical ventilation and was followed by manual external chest compressions and mechanical ventilation. After 3 minutes of resuscitation, piglets that did not achieve return of spontaneous circulation were randomized to two groups: adrenaline 0.02 mg kg–1 every 3 minutes (20 animals) and adrenaline 0.02 mg kg–1 every 3 minutes plus terlipressin 20 &mgr;g kg–1 every 6 minutes plus hydrocortisone 30 mg kg–1 one dose (22 animals). Resuscitation was discontinued when return of spontaneous circulation was achieved or after 24 minutes. Measurement and Main Results: Return of spontaneous circulation was achieved in 14 piglets (28.5%), 14.2% with only cardiac massage and ventilation. Return of spontaneous circulation was achieved in 25% of piglets treated with adrenaline and in 9.1% of those treated with adrenaline plus terlipressin plus hydrocortisone (p = 0.167). Return of spontaneous circulation was achieved in 45.4% of animals with pulseless electric activity, 20% with asystole, and 0% with ventricular fibrillation (p = 0.037). Shorter duration of cardiac arrest, higher mean blood pressure and EtCO2 and lower PaCO2 before resuscitation, and higher mean blood pressure during resuscitation were associated with higher return of spontaneous circulation. Conclusions: Treatment with adrenaline plus terlipressin plus corticoids does not achieve higher return of spontaneous circulation than that with adrenaline in an infant animal model of asphyxial cardiac arrest.

Infection in critically ill pediatric patients on continuous renal replacement therapy.

Introduction Continuous renal replacement therapies (CRRT) are frequently used in critically ill children and may increase the risk of infection. However, the incidence, characteristics and prognosis of infection in critically ill children on CRRT have not been studied. Methods Data from a prospective, single-center register of critically ill children treated with CRRT was analyzed. Results 55 children (40% under 1 year of age) were treated with CRRT between June 2008 and January 2012; 43 patients (78.2%) presented 1 or more infections. The most common condition of patients requiring CRRT was heart disease (69%). Infection occurred a median of 11 days after the initiation of CRRT (IQ range: 4 to 21 days). A total of 21 patients (48.8 %) developed 1 infection, 7 (16.2%) developed 2 infections and 15 (34.9%) developed 3 or more infections. The most frequent infection was catheter-related bacteremia, with no differences in catheter location. CRRT duration longer than 4.5 days was the only risk factor for infection. Patients with infection had a longer length of stay (LOS) in the Pediatric Intensive Care Unit (PICU) than patients without it (37.8 vs. 17.6, p = 0.019), but there were no differences in mortality (30.2% vs. 33.3%; p = 0.84). Conclusions Infection rate is high in critically ill children treated with CRRT. More than 4 days of CRRT increases the risk of infection. Infection in these patients entails a longer stay in the PICU but did not increase mortality.

Evaluation of sublingual microcirculation in a paediatric intensive care unit: prospective observational study about its feasibility and utility

BackgroundEvaluation of the microcirculation in critically ill patients is usually done by means of indirect parameters. The aim of our study was to evaluate the functional state of the microcirculation by direct visualization of sublingual microcirculation using Sidestream Dark Field Imaging, to determine the correlation between these findings and other parameters that are commonly used in the clinical practice and to assess the applicability of the systematic use of this technique in critically ill children.MethodsA prospective observational study was carried out in a Pediatric Intensive Care Unit (PICU) of a tertiary referral hospital. All patients admitted to the PICU during a three-month period were included in the study after obtaining the informed consent from the patient. Systematic evaluation of sublingual microcirculation was done in these patients (Total Vessel Density, Proportion of Perfused Vessels, Perfused Vessel Density, De Backer Score, Microvascular Flow Index, Heterogeneity Index) within the first day of admission (T1) and between the second and third day of admission (T2). Other clinical, hemodynamic, and biochemical parameters were measured and registered simultaneously. When the evaluation of the microcirculation was not feasible, the reason was registered. Descriptive analysis of our findings are expressed as means, medians, standard deviations and interquartile ranges. Mann–Whitney-Wilcoxon and Fisher tests were used to compare variables between patients with and without evaluation of the microcirculation. Pearson Correlation Coefficient (ρ) was used to evaluate the correlation between microcirculatory parameters and other clinical parameters.ResultsOne hundred fine patients were included during the study period. Evaluation of the microcirculation was feasible in 18 patients (17.1%). 95.2% of them were intubated. The main reason for not evaluating microcirculation was the presence of respiratory difficulty or the absence of collaboration (95.1% on T1 and 68.9% on T2). Evaluated patients had a higher prevalence of intubation and ECMO at admission (72.2% vs. 14.9% and 16.6% vs. 1.1%, respectively), and longer median duration of mechanical ventilation (0 vs. 6.5 days), vasoactive drugs (0 vs. 3.5 days) and length of stay (3 vs. 16.5 days) than non-evaluated patients. There was a moderate correlation between microcirculatory parameters and systolic arterial pressure, central venous pressure, serum lactate and other biochemical parameters used for motoring critically ill children.ConclusionsSystematic evaluation of microcirculation in critically ill children is not feasible in the unstable critically ill patient, but it is feasible in stable critically ill children. Microcirculatory parameters show a moderate correlation with other parameters that are usually monitored in critically ill children.

Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets

Objective To design an experimental pediatric animal model of acute kidney injury induced by cisplatin. Methods Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study. Results 41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage. Conclusions a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury.

Different Respiratory Rates during Resuscitation in a Pediatric Animal Model of Asphyxial Cardiac Arrest.

Aims Actual resuscitation guidelines recommend 10 respirations per minute (rpm) for advanced pediatric life support. This respiratory rate (RR) is much lower than what is physiological for children. The aim of this study is to compare changes in ventilation, oxygenation, haemodynamics and return of spontaneous circulation (ROSC) rates with three RR. Methods An experimental model of asphyxial cardiac arrest (CA) in 46 piglets (around 9.5 kg) was performed. Resuscitation with three different RR (10, 20 and 30 rpm) was carried out. Haemodynamics and gasometrical data were obtained at 3, 9, 18 and 24 minutes after beginning of resuscitation. Measurements were compared between the three groups. Results No statistical differences were found in ROSC rate between the three RR (37.5%, 46.6% and 60% in the 10, 20 and 30 rpm group respectively P = 0.51). 20 and 30 rpm groups had lower PaCO2 values than 10 rpm group at 3 minutes (58 and 55 mmHg vs 75 mmHg P = 0.08). 30 rpm group had higher PaO2 (61 mmHg) at 3 minutes than 20 and 10 rpm groups (53 and 45 mmHg P = 0.05). No significant differences were found in haemodynamics or tissue perfusion between hyperventilated (PaCO2 <30 mmHg), normoventilated (30–50 mmHg) and hypoventilated (>50 mmHg) animals. PaO2 was significantly higher in hyperventilated (PaO2 153 mmHg) than in normoventilated (79 mmHg) and hypoventilated (47 mmHg) piglets (P<0.001). Conclusions Our study confirms the hypothesis that higher RR achieves better oxygenation and ventilation without affecting haemodynamics. A higher RR is associated but not significantly with better ROSC rates.

Incidence and Prognosis of Acute Kidney Injury After Cardiac Arrest in Children

Background/Aims: The incidence of acute kidney injury (AKI) after cardiac arrest (CA) in adults is associated with a high mortality, but there are few data about the incidence and prognosis of AKI after CA in children. The aim of our study was to analyze the incidence of AKI in children who have experienced an in-hospital CA and its association with mortality. Methods: A retrospective observational study in a prospective database was performed including children between the ages 1 month and 16 years, who had undergone an in-hospital CA. Information on clinical, analytical, and monitorization data, treatment, mortality and cause of death were recorded. Results: Fifty-six children were included in the study (57.6% males). Return of spontaneous circulation (ROSC) was achieved in 49 children (87.7%). Thirty-one patients (55.3%) survived. Four patients (8.1%) were being treated with continuous renal replacement therapies (CCRT) before CA. After ROSC, 7 other children (14.3%) had severe acute kidney injury requiring CRRT. Mortality of children who required CRRT after CA (57.1%) was not significantly higher than that in children who did not (26.3%; p = 0.18). But mortality of patients who need CRRT before or after CA (72.7%) was significantly higher than the remaining patients (26.3%; p = 0.03). Conclusions: The frequency of AKI in children after recovering a CA is moderate. AKI that needs CCRT before or after CA is associated with a higher mortality.

Comparison between manual and mechanical chest compressions during resuscitation in a pediatric animal model of asphyxial cardiac arrest

Aims Chest compressions (CC) during cardiopulmonary resuscitation are not sufficiently effective in many circumstances. Mechanical CC could be more effective than manual CC, but there are no studies comparing both techniques in children. The objective of this study was to compare the effectiveness of manual and mechanical chest compressions with Thumper device in a pediatric cardiac arrest animal model. Material and methods An experimental model of asphyxial cardiac arrest (CA) in 50 piglets (mean weight 9.6 kg) was used. Animals were randomized to receive either manual CC or mechanical CC using a pediatric piston chest compressions device (Life-Stat®, Michigan Instruments). Mean arterial pressure (MAP), arterial blood gases and end-tidal CO2 (etCO2) values were measured at 3, 9, 18 and 24 minutes after the beginning of resuscitation. Results There were no significant differences in MAP, DAP, arterial blood gases and etCO2 between chest compression techniques during CPR. Survival rate was higher in the manual CC (15 of 30 = 50%) than in the mechanical CC group (3 of 20 = 15%) p = 0.016. In the mechanical CC group there was a non significant higher incidence of haemorrhage through the endotracheal tube (45% vs 20%, p = 0.114). Conclusions In a pediatric animal model of cardiac arrest, mechanical piston chest compressions produced lower survival rates than manual chest compressions, without any differences in hemodynamic and respiratory parameters.