Clinical Guidelines for Routine Neuromonitoring in Neonatal and Pediatric Patients Supported on Extracorporeal Membrane Oxygenation.

DISCLAIMER: These guidelines for routine neuromonitoring in neonatal and pediatric patients supported on extracorporeal membrane oxygenation (ECMO) are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing extracorporeal life support (ECLS)/ECMO and describe what are believed to be useful and safe practice for ECLS and ECMO but these are not necessarily consensus recommendations. The aim of clinical guidelines was to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge, and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or being deemed inclusive of all proper methods of care nor exclusive of other methods of care directed at obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient considering all the circumstances presented by the individual patient, and the known variability and biologic behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

Extracorporeal Life Support Organization (ELSO) Guidelines for Follow-up After Neonatal and Pediatric Extracorporeal Membrane Oxygenation.

Neonates and children who have survived critical illness severe enough to require extracorporeal membrane oxygenation (ECMO) are at risk for neurologic insults, neurodevelopmental delays, worsening of underlying medical conditions, and development of new medical comorbidities. Structured neurodevelopmental follow-up is recommended for early identification and prompt interventions of any neurodevelopmental delays. Even children who initially survive this critical illness without new medical or neurologic deficits remain at risk of developing new morbidities/delays at least through adolescence, highlighting the importance of structured follow-up by personnel knowledgeable in the sequelae of critical illness and ECMO. Structured follow-up should be multifaceted, beginning predischarge and continuing as a coordinated effort after discharge through adolescence. Predischarge efforts should consist of medical and neurologic evaluations, family education, and co-ordination of long-term ECMO care. After discharge, programs should recommend a compilation of pediatric care, disease-specific care for underlying or acquired conditions, structured ECMO/neurodevelopmental care including school performance, parental education, and support. Institutionally, regionally, and internationally available resources will impact the design of individual center's follow-up program. Additionally, neurodevelopmental testing will need to be culturally and lingually appropriate for centers' populations. Thus, ECMO centers should adapt follow-up program to their specific populations and resources with the predischarge and postdischarge components described here.

Pediatric Chronic Critical Illness: Validation, Prevalence, and Impact in a Children's Hospital.

OBJECTIVES: Large populations of chronically critically ill patients test the critical care system's resource utilization ability. Defining and tracking this group is necessary for census predictions. DESIGN: Retrospective cohort analysis. SETTINGS: Tertiary academic center in United States. PATIENTS: Patients admitted to PICU or neonatal ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics and resource utilization variables were sampled in PICU, intermediate care unit, cardiovascular ICU, and neonatal ICU on 3 random days in 3 consecutive months. The attendings' perception of pediatric chronic critical illness was contrasted to Shapiro's definition of chronic critical care criteria. Each unit's active and maximal capacity census was computed: the occurrence rate of pediatric chronic critical illness was 34%, the prevalence was 44.5%, and the tolerance, or percentage pediatric chronic critical illness patients to all available beds, was 36.8%. The median length of stay for the nonpatients with pediatric critical care illness to patients with pediatric critical care illness was 9 versus 46 days (1/5.1). The attending's decision was 58 times more concordant with the criteria. Pediatric chronic critical illness bed occupancy was 40.6% in PICU, 97.2% in intermediate care unit, 47.8% in cardiovascular ICU, and 33.9% in neonatal ICU. CONCLUSIONS: Pediatric chronic critical illness patients occupied more than one third of the ICU beds and have five times longer stay. This mounting load needs to be uniformly defined, addressed at regional and national levels, and considered in the current pandemic planning.

Differential Role of Rapamycin and Torin/KU63794 in Inflammatory Response of 264.7 RAW Macrophages Stimulated by CA-MRSA.

Background. Rapamycin suppresses the RAW264.7 macrophage mediated inflammatory response but in lower doses induces it. In the present study, we tested the suppression of the inflammatory response in the presence of mTOR 1 and 2 inhibitors, Torin and KU63794. Methods. RAW264.7 cells were stimulated for 18 hrs with 10(6) to 10(7) CFU/mL inocula of community-acquired- (CA-) MRSA isolate, USA400 strain MW2, in the presence of Vancomycin. Then, in sequential experiments, we added Torin, KU63794, and Rapamycin alone and in various combinations. Supernatants were collected and assayed for TNF, IL-1, IL-6, INF, and NO. Results. Rapamycin induces 10-20% of the inflammatory cascade at dose of 0.1 ng/mL and suppresses it by 60% at dose of 10 ng/mL. The induction is abolished in the presence of Torin KU63794. Torin and KU63794 are consistently suppressing cytokine production 50-60%. Conclusions. There is a differential response between Rapamycin (mTOR-1 inhibitor) and Torin KU63794 (mTOR 1 and 2 inhibitors). Torin and KU63794 exhibit a dose related suppression. Rapamycin exhibits a significant induction-suppression biphasic response. Knowledge of such response may allow manipulation of the septic inflammatory cascade for clinical advantages.

Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages.

Background. Methicillin-resistant Staphylococcus aureus (MRSA) can stimulate massive cytokine release. Ketamine suppresses tumor necrosis factor (TNF) secretion by MRSA-stimulated RAW264.7 macrophages, and the mechanism likely involves N-methyl-D-aspartic acid (NMDA) receptor antagonism. The downstream effects of NMDA-mediated TNF suppression, specifically the PI3K/Akt and mTOR modulation, have not been described. Methods. RAW264.7 cells were stimulated for 18 hrs with 10(5) to 10(7) CFU/mL inocula of either of two prototypical community-acquired- (CA-) MRSA isolates, USA300 strain LAC and USA400 strain MW2. Then we added the NMDA inhibitors ketamine or 2R-amino-5-phosphonopentanoate (AP5), NMDA substrate, LY294002, and rapamycin in various combinations. Results. NMDA inhibition suppressed TNF secretion by almost a third compared to the no-ketamine control. When NMDA substrate was added, the TNF secretion increased by 10%. Addition of LY294002 suppressed TNF production by macrophages by 20%. Rapamycin exhibited a concentration-dependent TNF induction-suppression response: induction at doses of 0.1 and 1 ng/mL and suppression at 10 and 100 ng/mL. Induction of TNF was abolished when LY294002 was added and the suppression became uniform. Ketamine-induced suppression of TNF secretion was intensified 10-15% when rapamycin was added, but not when LY294002 was added. Conclusion. These findings suggest that NMDA-induced TNF suppression can be augmented by concurrent mTOR inhibition.