Matteo Di Nardo

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.

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.

Adoptive immunotherapy with antigen-specific T cells during extracorporeal membrane oxygenation (ECMO) for adenovirus-related respiratory failure in a child given haploidentical stem cell transplantation.

We report on the successful infusion of human adenovirus (HAdV)‐specific T cells in a child with congenital amegakaryocytic thrombocytopenia, given T‐cell‐depleted hematopoietic stem cell transplantation (HSCT) from the HLA‐haploidentical mother during extracorporeal membrane oxygenation (ECMO) for severe HAdV‐related respiratory failure. Donor‐derived, interferon (IFN)‐γ‐secreting HAdV‐specific T cells were enriched using the cytokine capture assay, after in vitro stimulation with overlapping peptides from the immunodominant HAdV5 hexon protein. Two weeks after T‐cell transfer, viral load decreased and ECMO was discontinued. T‐cell responses to HAdV antigens were documented after four weeks and were associated with viral clearance, immune reconstitution and clinical amelioration. Pediatr Blood Cancer 2014;61:376–379.

Extracorporeal membrane oxygenation as a bridge to allogeneic T-cell depleted hematopoietic stem cell transplantation in infants with severe combined immune deficiency: is it feasible?

Dear Editor, Because severe combined immunodeficiency (SCID) is usually lethal within the first year of life [1], diagnosis and treatment must be established rapidly. Although gene therapy is currently investigated for some SCID variants, the most widely employed treatment is still represented by allogeneic hematopoietic stem cell transplantation (allo-HSCT) [2]. The therapeutic benefit of alloHSCT is frequently offset by respiratory failure (RF) due to opportunistic infections occurring both before and after transplantation. Few attempts have been made to manage RF with extracorporeal membrane oxygenation (ECMO) during the aplastic phase following allo-HSCT. Leahey et al. [3] reported successful use of ECMO post-transplant in SCID patients with bronchiolitis; however, a recent review of 29 cases of ECMO posttransplant indicates that patient outcome is dismal [4]. To the best of our knowledge, no one has reported ECMO as a ‘‘bridge to allo-HSCT’’ in SCID patients. We describe the case of a 6-month-old boy with c-chain deficiency SCID, supported with ECMO before and after T cell depleted allo-HSCT from his HLAhaploidentical mother for RF. This child was referred to our hospital for diarrhea, dehydration, and RF [pH 7.48, PaO2/FiO2 280, PaCO2 4 kPa (30 mmHg)]. Chest X-ray showed bilateral consolidations. He was immediately admitted to the pediatric intensive care unit (PICU), where helmet continuous positive-airway pressure [0.5 kPa (5 cmH2O), FiO2 0.6] was started. However, as a result of respiratory fatigue, we decided to intubate the patient. Bronchoalveolar lavage (BAL) was positive for cytomegalovirus (CMV) and Pneumocystis jirovecii (PJ); thus, intravenous ganciclovir and trimethoprim were started. Although on mechanical ventilation, gas exchange worsened (Fig. 1) and ECMO was started. The child was supported with VV-ECMO using a double-lumen 16-F Avalon cannula (Maquet, Getinge Group, Germany), inserted percutaneously from the right jugular vein. A centrifugal pump (Pedivas, Levitronix, Thoratec, UK) with a phosphorylcholine fully coated oxygenator (Pediatric ECMO A.L. ONE, Eurosets Medolla, Italy) and a phosphorylcholine fully coated 1/4 circuit (Eurosets, Medolla, Italy) were used. The patient received reducedintensity regimen including treosulfan and fludarabine. A novel graft manipulation with a/b T and CD19? B cell depletion (Miltenyi

Neurologic Injury in Adults Supported With Veno-Venous Extracorporeal Membrane Oxygenation for Respiratory Failure: Findings From the Extracorporeal Life Support Organization Database

Objectives: To assess in-hospital neurologic (CNS) complications in adult patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure. Design: Retrospective analysis of the Extracorporeal Life Support Organization’s data registry. Setting: Data reported to Extracorporeal Life Support Organization from 350 international extracorporeal membrane oxygenation centers during 1992–2015. Patients: Adults (≥ 18 yr old) supported with veno-venous extracorporeal membrane oxygenation for respiratory failure. Interventions: None. Measurements and Main Results: We included 4,988 adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure. Neurologic injury was defined as brain death, seizures, stroke, and intracranial hemorrhage occurring during extracorporeal membrane oxygenation support. We used multivariable logistic regression to explore patient and extracorporeal membrane oxygenation factors associated with neurologic injury. Median age of the study cohort was 46 (interquartile range, 32–58). Four hundred twenty-six neurologic complications were reported in 356 patients (7.1%), and included 181 intracranial hemorrhage (42.5%), 100 brain deaths (23.5%), 85 stroke (19.9%), and 60 seizure events (14.1%). In-hospital mortality was significantly higher for those with CNS complications (75.8% vs 37.8%; p < 0.001) and varied by type of CNS injury; mortality was 79.6% in patients with intracranial hemorrhage, 68.2% in patients with stroke, and 50% in patients with seizures. Pre-extracorporeal membrane oxygenation cardiac arrest, continuous veno-venous hemofiltration, and hyperbilirubinemia during extracorporeal membrane oxygenation were associated with increased odds of neurologic injury. Conclusions: Approximately 7% of adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure had neurologic injury. Intracranial hemorrhage was the most frequent type, and survival for patients with neurologic injury was poor. Future investigations should evaluate anticoagulation management as well as brain/extracorporeal membrane oxygenation interaction to reduce these life-threatening events.

ECLS in Pediatric Cardiac Patients

Extracorporeal life support (ECLS) is an important device in the management of children with severe refractory cardiac and or pulmonary failure. Actually, two forms of ECLS are available for neonates and children: extracorporeal membrane oxygenation (ECMO) and use of a ventricular assist device (VAD). Both these techniques have their own advantages and disadvantages. The intra-aortic balloon pump is another ECLS device that has been successfully used in larger children, adolescents, and adults, but has found limited applicability in smaller children. In this review, we will present the “state of art” of ECMO in neonate and children with heart failure. ECMO is commonly used in a variety of settings to provide support to critically ill patients with cardiac disease. However, a strict selection of patients and timing of intervention should be performed to avoid the increase in mortality and morbidity of these patients. Therefore, every attempt should be done to start ECLS “urgently” rather than “emergently,” before the presence of dysfunction of end organs or circulatory collapse. Even though exciting progress is being made in the development of VADs for long-term mechanical support in children, ECMO remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation. With the increase in familiarity with ECMO, new indications have been added, such as extracorporeal cardiopulmonary resuscitation (ECPR). The literature supporting ECPR is increasing in children. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS have reduced in the last 5 years and many centers support patients with functionally univentricular circulations. Improved results have been recently achieved in this complex subset of patients.

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.

Brain monitoring in adult and pediatric ECMO patients: The importance of early and late assessments

Monitoring brain integrity and neurocognitive function is a new and important target for the management of a patient treated with extracorporeal membrane oxygenation (ECMO), in particular because of the increasing awareness of cerebral abnormalities that may potentially occur in this setting. Continuous regular monitoring, as well as repeated assessment for cerebral complications has become an essential element of the ECMO patient management. Besides well-known complications, like bleeding, ischemic stroke, seizures, and brain hypoperfusion, other less defined yet relevant injury and clinical manifestations are increasingly reported and impacting on ECMO patient prognosis at short term. Furthermore, it is becoming more evident that neurologic complication may not occur only in the early phase. Indeed, other potential adverse events related to the long-term neurocognitive function have been also recently documented either in children or adult ECMO patients. Despite increasing awareness of these aspects, generally accepted protocols and clinical management strategies in this respect are still lacking. Current means to monitor brain perfusion or detecting ongoing cerebral tissue injury are rather limited, and most techniques provide indirect or post-insult recognition of irreversible tissue injury. Continuous monitoring of brain perfusion, serial assessment of brain-derived serum biomarkers, timely neuro-imaging, and post-discharge counselling for neurocognitive dysfunction, particularly in pediatric patients, are novel pathways focusing on neurologic assessment with important implications in daily practice to assess brain function and integrity not only during the ECMO-related hospitalization, but also at long-term to re-evaluate the neuropsychological integrity, although well designed studies will be necessary to elucidate the cost-effectiveness of these management strategies.

Cannulating the contraindicated: effect of low birth weight on mortality in neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation

BACKGROUND/PURPOSE Restrictions for ECMO in neonates include birth weight less than 2kg (BW <2kg) and/or gestational age less than 34weeks (GA <34weeks). We sought to describe their relationship on mortality. METHODS Neonates with a primary diagnosis code of CDH were identified in the Extracorporeal Life Support Organization (ELSO) registry, and logistic regression models were used to examine the effect of BW <2kg and GA <34weeks on mortality. RESULTS We identified 7564 neonates with CDH. The overall mortality was 50%. There was a significantly higher risk of death with unadjusted odds ratio (OR) 2.39 (95% confidence interval [CI]: 1.53-3.74; P<0.01) for BW <2kg neonates. The adjusted OR of death for BW <2kg neonates remained significantly high with over two-fold increase in the odds of mortality when adjusted for potential confounding variables (OR 2.11, 95% CI: 1.30-3.43; P<0.01). However, no difference in mortality was observed in neonates with GA <34weeks. CONCLUSIONS While mortality among CDH neonates with a BW <2kg was substantially increased, GA <34weeks was not significantly associated with mortality. Effort should be made to identify the best candidates for ECMO in this high-risk group and develop treatment strategies to optimize their survival. TYPE OF STUDY Case-Control Study, Retrospective Comparative Study. LEVEL OF EVIDENCE Level III.