Francesca Stoppa

Impact of severe sepsis on serum and urinary biomarkers of acute kidney injury in critically ill children: an observational study.

Background/Aims: We hypothesized that sepsis could have an impact on the sensitivity of serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) for acute kidney injury (AKI) diagnosis in critically ill children. Methods: Serum NGAL (sNGAL) and urinary NGAL (uNGAL) and CysC were measured daily in the first 48 h from pediatric intensive care unit admission in 11 consecutive critically ill children with severe sepsis; a single measurement was made in a population of 10 healthy controls undergoing minor ambulatory surgery to exclude possible biases in the laboratory methods. Results: uNGAL, serum CysC (sCysC), and urinary CysC (uCysC) levels were significantly increased in patients with septic AKI compared with septic patients without AKI, while sNGAL levels were not significantly different between septic patients with and without AKI. Median serum creatinine levels did not show significant differences between AKI and non-AKI patients. Conclusions: uNGAL, sCysC and uCysC were not altered by sepsis and were good predictors of AKI. In a septic state, sNGAL alone did not discriminate patients with AKI from those without AKI.

Relationship between global end-diastolic volume and cardiac output in critically ill infants and children

Objective:The objective of this study was to investigate possible correlations between the preload index global end-diastolic volume (GEDV) and the indexes of cardiac function, cardiac index, and stroke volume index in critically ill pediatric patients. The aim was to evaluate whether GEDV may help in the decision-making process concerning volume loading. Design:Prospective clinical study. Setting:Pediatric intensive care unit of the Bambino Gesù Children’s Research Hospital. Patients:Seventy patients, 40 male and 30 female, mean age 62 ± 41 months (range 5–156 months), divided into six groups: group A, hemorrhagic shock, ten cases; group B, head injury, 21 cases; group C, septic shock, ten cases; group D, encephalitis, ten cases; group E, respiratory failure, nine cases; group F, cardiogenic shock, ten cases. Interventions:All patients received volumetric hemodynamic monitoring following initial resuscitation and every 4 hrs thereafter or whenever a hemodynamic deterioration was suspected. During the cumulative in-hospital stay, a total 1,184 sets of measurements were done. Measurements and Main Results:Findings are consistent with a statistically significant linear correlation of GEDV with cardiac index and stroke volume index in hemorrhagic shock (group A) (R2 = .647, p < .0001; R2 = .738, p < .0001) and cardiogenic shock (group F) (R2 = .645, p < .0001; R2 = .841, p < .0001). Conclusions:GEDV may potentially be a useful guide to treatment in preload-dependent conditions, such as hemorrhagic and cardiogenic shock. In the other groups where there is little relationship between preload and cardiac function indexes, the influence of non-preload-dependent mechanisms on cardiac output is certainly more significant.

Ultrasound-guided central venous cannulation in infants weighing less than 5 kilograms

Purpose Recent reports suggest that ultrasound-guided central venous cannulation may also be safe and effective in infants. This study aimed to evaluate the success and complications rate of this technique in infants weighing less than 5 kg. Methods We studied 45 infants, weighing less than 5 kg (mean weight: 2.9 ± 1.1 kg, median: 3.1) needing a central venous access for intensive care treatment. In all patients, venous access was obtained by ultrasound-guided cannulation of the internal jugular vein (IJV). Results Central venous cannulation was successful in all 45 infants. The right internal jugular vein (IJV) was used in most cases (92%). The IJV was antero-lateral to the carotid artery in 66% of patients, lateral in 28% and anterior in 6%. Although we recorded 10 complications (22.2%), only one was clinically relevant (one pneumothorax). The other complications were repeated venipunctures (n=4), kinking of the guidewire (n=3) and local venous hematomas (n=2). The time required for completing the procedure was 7 ± 4.3 min, while the mean time of central venous catheter permanence was 5.5 ± 8 days. There was a negative correlation between the patients weight and the time needed for cannulation (p<0.01). Complications occurred in infants with a lower body weight (p<0.01). Conclusions Our experience suggests that ultrasound-guided central vein cannulation can be performed by well-trained physicians in infants weighing less than 5 kg without relevant risks.

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01).

Introduction Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as ‘refractory’ (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. Trial registration number NCT02431663; Pre-results.

Ultrasound-guided left brachiocephalic vein cannulation in children with underlying bleeding disorders: A retrospective analysis

Objectives: To evaluate the safety and effectiveness of ultrasound–guided left brachiocephalic vein cannulation in infants and children with underlying bleeding conditions. Design: Retrospective cohort. Setting: PICU of a tertiary pediatric hospital. Patients: Thirty-four patients requiring central venous catheterization from January 2011 to January 2012. Interventions: None. Measurements and Main Results: Two pediatric intensivists, experienced in ultrasound–guided vessel cannulation, performed the ultrasound catheterization of the left brachiocephalic vein. Ultrasound equipment consisted of a standard ultrasound monitor with a linear 6–13 MHz probe. The ultrasound monitor was set on a resolution with a depth of 1.8 cm for infants and 2.2 cm for children. The “in-plane” technique was used for all patients. Thirty-four catheterizations were performed. Patient median age was 12.5 months (5.75–63.5 mo) and median weight was 9.25 kg (7–16.25 kg). The population of infants and children analyzed was composed of 25 patients with hematologic disorder (73%) treated with hematopoietic stem cell transplantation, five patients (15%) supported with extracorporeal membrane oxygenation for viral pneumonias, and four patients (12%) with uremic hemolytic syndrome. A 4F catheter was used in 79% of cases. Left brachiocephalic vein cannulation was successful in all 34 patients. Median time needed for cannulation was 350 seconds (277.5–450 s). The overall complication rate was 9% (3 of 34) and consisted of difficulty in advancing the guidewire after having pierced the vein. The time required for catheter positioning and complications was not associated with both lower body weight and body surface area of the patients (p > 0.05). Mean central venous catheter duration was 32 ± 4 days. Conclusions: Data reported in this retrospective study confirm the safety and effectiveness of ultrasound–guided left brachiocephalic vein catheterization in infants and children with underlying bleeding disorders.

Independent lung ventilation in a newborn with asymmetric acute lung injury due to respiratory syncytial virus: A case report

IntroductionIndependent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients.Case presentationWe present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weight who had an asymmetric lung injury due to respiratory syncytial virus bronchiolitis. We used independent lung ventilation applying conventional protective pressure controlled ventilation to the less-compromised lung, with a respiratory frequency proportional to the age of the patient, and a pressure controlled high-frequency ventilation to the atelectatic lung. This was done because a single tube conventional ventilation protective strategy would have exposed the less-compromised lung to a high mean airways pressure. The target of independent lung ventilation is to provide adequate gas exchange at a safe mean airways pressure level and to expand the atelectatic lung. Independent lung ventilation was accomplished for 24 hours. Daily chest radiograph and gas exchange were used to evaluate the efficacy of independent lung ventilation. Extubation was performed after 48 hours of conventional single-tube mechanical ventilation following independent lung ventilation.ConclusionThis case report demonstrates the feasibility of independent lung ventilation with two separate tubes in neonates as a treatment of an asymmetric acute lung injury.

Abdominal compartment syndrome in childhood: the role of near infrared spectroscopy for the early detection of the organ dysfunction

We found very interesting the manuscript written by Dr. Steinau et al. [1] recently published in your journal. The author proposed their approach for the management of abdominal compartment syndrome (ACS) in childhood presenting a wide case mix of pathology ranging from neonates to school children. We agree that the gold standard for the indirect intrabdominal preassure (IAP) measurement both in adults and children is the intra-bladder pressure monitoring with an intermittent saline bolus. In accordance with the adult guidelines, intrabdominal hypertension (IAH) in children is firstly managed with a conservative therapy, while in the presence of ACS (low abdominal perfusion pressure associated to a new onset of organ dysfunction) early abdominal decompression remains a mandatory approach in order to reduce the high mortality rate associated with this condition [2, 3]. Unfortunately, the ‘‘numbers’’ used in the adult population to perform an abdominal decompression are not applicable in children since the variable abdomen compliance especially in neonates and infants [2]. Many authors [1, 2, 4] suggested proper cut-off values for IAH, to establish the ‘‘critical pressure number’’ at which regularly a switch from IAH to ACS in pediatric patients can be observed. In his work, Dr. Steinau et al. used the criteria proposed by Dr. Eijke [4] to define the pediatric ACS [3]. He considered the pediatric ACS as a lasting IAH higher than 12 mmHg combined with at least one organ dysfunction. We believe that a fixed ‘‘critical’’ number is not suitable for all pediatric patients and that the values proposed by Dr. Stainau are just indicative of an evolving process that could lead or not to a multiple organ dysfunction. Both in adults and children, clinical examination and laboratory testing (base deficit, lactate, unpaired dieresis) are sensitive in detecting abnormalities of tissue perfusion during ACS only after sustained periods of inadequate perfusion, furthermore the early changes in organ metabolism are not easily identified with the traditional monitoring systems. We believe that the outcome of ACS would improve if an earlier detection of regional tissue hypoperfusion would be provided to these patients. Differently from adults, in both neonates and infants, abdominal organs perfusion (kidney) can be monitored using the near infrared spectroscopy (NIRS). This device enables the detection of the states of organ hypoperfusion, allowing a rapid intervention to limit the cascade of multiple organs dysfunction and the development of shock [5–7]. NIRS uses nonpulsatile oximetry to determine venous-weighted oxy-hemoglobin saturation of the underlying regional tissue (rSO2) studied. In pediatrics generally two-site NIRS (brain–kidney) is used for the non invasive assessment of the cardiac output and of its autoregulation in the case of shock [6]. Normally tissue beds with high oxygen consumption (brain) have lower baseline rSO2, where tissue with little metabolic demand (kidney) have a higher baseline rSO2. Figure 1 shows a case of primary ACS for a Clostridium difficilis enterocolitis in a 6-month-old child (7 kg body weight) in which two-site NIRS (brain–kidney) was continuously used to manage the relation between cardiac output and IAP. This patient presented a pathologic change in brain and kidney saturation (dotted arrow) when IAP was *10 mmHg and diuresis was still 1.5 ml/kg/h. This state was not controlled with the medical therapy (deep sedation, neuromuscular M. Di Nardo (&) C. Cecchetti F. Stoppa N. Pirozzi S. Picardo Pediatric Intensive Care Unit, Children’s Hospital Bambino Gesu, Rome, Italy e-mail: matteo.dinardo@tin.it

Severe parainfluenza pneumonia in a case of transient hypogammalobulinemia of infancy.

Human parainfluenza viruses (HPIVs) infection, largely known to cause self-limiting bronchiolitis and pneumonia in immune competent patients, can lead to severe to fatal pulmonary disease in immune disorders, such as primary or acquired-immune deficiencies. We report the case of a 1-year-old child who developed an acute respiratory distress syndrome. Because of a progressive respiratory failure unresponsive to conventional treatment extracorporeal membrane oxygenation (ECMO) was rapidly started. HPIV-3 infection was diagnosed on the rhinopharyngeal fluid and immunological examinations revealed a hypogammaglobulinemia. A combination therapy with ribavirin, intravenous immunoglobulin (IVIG) and steroid under ECMO support was started with considerable improvement. Subsequent analysis and more specific immunological assessment resulted normal confirming the diagnosis of transient hypogammaglobulinemia of infancy (THI). This case highlights the importance of prompt therapy with early ECMO support in combination with ribavirin, IVIG and steroids in patients affected by severe HPIV-3 pneumonia and THI.

Case 1: Chocolate-coloured blood in infant with shock (Case Presentation)

CASE PRESENTATION We report the case of a 6-month-old infant (body weight 6 kg), transferred to our intensive care unit (ICU) from a district general hospital with the diagnosis of septic shock. Upon arrival at our institution she was ventilated in a pressure-controlled mode reaching a peripheral Spo2 of 90% with a Fio2 of 100%, associated with a peripheral pallid cyanosis. Haemodynamic conditions were unstable: blood pressure 60/20 mmHg, heart rate 170 beats/min, refill capillary time >4 sec, reduced cardiac inotropic performance at trans-thoracic echocardiography without congenital anomaly. Neurologic examination showed a paediatric Glascow coma score (GCS) of 8, isocoric and isociclic pupils scarcely reacting to light bilaterally. Arterial blood gases showed a severe metabolic acidosis: pH: 7, Pao2, 218 mmHg, PaCo2, 14 mmHg, EB, −25. Blood haemoglobin was 9 g/L, leukocyte count 35 000/103 mcL, serum levels of sodium, potassium, calcium, phosphorus, urea, creatinine, liver enzymes, reactive C protein were within normal limits. A chest X-ray showed normal cardiac silhouette and clear lung fields. No signs of infections seemed to be present. Blood samples were brown coloured. After fluid administration of 20 mL/kg in 20 min of cristalloids and inotropic support (dopamine 10 g/kg/min) haemodynamic conditions progressively worsened leading to a cardiac arrest with asystolia. Cardiopulmonary resuscitation was successfully performed with a ROSC time of 100 sec. At this moment we were able to perform a better evaluation of patient’s clinical case history taken from the parents (they referred that the infant, previously healthy, progressively decreased her consciousness and that she was fed with a vegetable soup prepared in advance and stored in the refrigerator 2 days before admission to ICU). What caused her symptoms?

The first five years of neonatal and pediatric transports on extracorporeal membrane oxygenation in the center and south of Italy: The pediatric branch of the Italian “Rete Respira” network:

Introduction: Neonatal and pediatric ECMO is a high-risk procedure that should be performed only in expert centers. Children who are eligible for ECMO and are managed in hospitals without ECMO capabilities should be referred to the closest ECMO center before the severity of illness precludes safe conventional transport. When the clinical situation precludes safe conventional transport, ECMO should be provided on site with the patient transported on ECMO. Methods: We retrospectively reviewed our institutional database of all ECMO transports for neonatal and pediatric respiratory failure from February 2013 to February 2018. Results: Over the last 5 years, we provided 24 transports covering all requests from the center and south of Italy except for the islands. Of these transports, 20 were performed on ECMO and 4 without ECMO. No patient died during transportation. Five complications were reported only during the ECMO transports, and all of these were managed without compromising the patient’s safety. The preferred modes of transport were by ambulance (70%) and ambulance transported into the fixed wing aircraft (30%) for longer national distances. The survival to hospital discharge of the patients transported with ECMO was 75% among the neonatal transports and 83.3% among the pediatric transports. The survival to hospital discharge of the four patients transported without ECMO was 100% for both neonates and children. Conclusions: Neonatal and pediatric ECMO transports can be safely performed with a dedicated team that maintains stringent adherence to well-designed management protocols.