History of prematurity and the patient's age did not increase a patient's risk of failure. Nonresponders to high-flow nasal cannula therapy were on the onset, more hypercarbic, were less tachypnic prior to the start of high-flow nasal cannula, and had no change in their respiratory rate after the initiation of high-flow nasal cannula therapy. Nonresponders had higher pediatric risk of mortality scores in the first 24 hrs.

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Pertussis carries a high risk of mortality in very young infants. The mechanism of refractory cardio-respiratory failure is complex and not clearly delineated. We aimed to examine the clinico-pathological features and suggest how they may be related to outcome, by multi-center review of clinical records and post-mortem findings of 10 patients with fulminant pertussis (FP). All cases were less than 8 weeks of age, and required ventilation for worsening respiratory symptoms and inotropic support for severe hemodynamic compromise. All died or underwent extra corporeal membrane oxygenation (ECMO) within 1 week. All had increased leukocyte counts (from 54 to 132 x 10(9)/L) with prominent neutrophilia in 9/10. The post-mortem demonstrated necrotizing bronchitis and bronchiolitis with extensive areas of necrosis of the alveolar epithelium. Hyaline membranes were present in those cases with viral co-infection. Pulmonary blood vessels were filled with leukocytes without well-organized thrombi. Immunodepletion of the thymus, spleen, and lymph nodes was a common feature. Other organisms were isolated as follows; 2/10 cases Para influenza type 3, 2/10 Moraxella catarrhalis, 1/10 each with respiratory syncytial virus (RSV), a coliform organism, methicillin-resistant Staphylococcus aureus (MRSA), Haemophilus influenzae, Stenotrophomonas maltophilia, methicillin-sensitive Staphylococcus aureus (MSSA), and candida tropicalis. We postulate that severe hypoxemia and intractable cardiac failure may be due to the effects of pertussis toxin, necrotizing bronchiolitis, extensive damage to the alveolar epithelium, tenacious airway secretions, and possibly leukostasis with activation of the immunological cascade, all contributing to increased pulmonary vascular resistance. Cellular apoptosis appeared to underlay much of these changes. The secondary immuno-compromise may facilitate co-infection.

Intracellular heat shock protein 72 (Hsp72) is known to serve a broad cytoprotective role. Recent data indicate that stressed cells can release Hsp72 into the extracellular compartment, although the biological function of extracellular Hsp72 remains to be fully elucidated. Because extracellular Hsp72 has been demonstrated to interact with Toll-like receptor 4, we hypothesized that endogenously produced and released Hsp72 would reprogram the mononuclear cell responses to LPS. THP-1 cells treated with LPS were used as a model for nuclear factor (NF)–κB activation. Heat shock conditions consisted of incubation at 43°C for 1 h. Control cells were incubated at 37°C. Twenty four hours after incubation, heat shock conditioned media (HSCM) and control media (CM) were centrifuged, and the respective cells were discarded. A separate group of naive THP-1 cells were then incubated with either HSCM or CM for 18 h and then stimulated with LPS (1 µg/mL). Heat shock significantly increased Hsp72 in HSCM compared with CM. In THP-1 cells transfected with an NF-κB luciferase reporter plasmid, the addition of HSCM attenuated subsequent LPS-mediated luciferase activity compared with cells incubated in CM. The addition of HSCM also attenuated LPS-mediated NF-κB–DNA binding and IκBα degradation. Heat shock protein 72–mediated inhibition of NF-κB activation was further corroborated by a significant decrease in TNF-α production. When HSCM and CM were subjected to Hsp72 depletion via adenosine triphosphate–agarose binding, LPS-mediated activation of NF-κB was partially restored, suggesting that Hsp72 is partially responsible for cellular reprogramming in response to HSCM. These data demonstrate that endogenously produced and released extracellular Hsp72 has the ability to reprogram the in vitro response to endotoxin in cultured human mononuclear cells.

Computerized provider order entry (CPOE) and clinical decision support improve medication prescribing safety in adults. However, effective therapy for children requires dosing based on circulating medication levels. We examined the introduction of a computerized corollary order for aminoglycoside blood level monitoring. The study was divided into baseline (BP) and corollary order (CP) periods. In the CP, we implemented a workflow-integrated reminder to order blood levels and presented this to the clinician during each aminoglycoside ordering session. Appropriate laboratory monitoring was 128/159 (80.5%) courses in the BP and 146/177 (82.5%) courses in the CP. Thus introduction of the order did not significantly improve laboratory monitoring rates, nor did it result in a reduction in the rate of either toxic or subtherapeutic levels. However, aminoglycoside corollary orders may have an important role in institutions where pharmacists are not actively involved in monitoring therapy.

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Pediatric sepsis comprises a spectrum of disorders that result from infection by bacteria, viruses, fungi, or parasites. Sepsis ranges from bacteremia, with early signs of circulatory compromise to complete collapse with multiple organ dysfunction and death. Early recognition improves outcomes for infants and children. Over the past two decades, sepsis has been defined and redefined with modifications for the pediatric population. The most recent iteration, complementing the NICE guideline (NG51) “Sepsis: Recognition, diagnosis and early management”, was published in 2017.1 Pediatric severe sepsis usually is community-acquired (57%) with the respiratory tract as the primary site of infection. Mortality rates associated with sepsis and septic shock in patients admitted to the pediatric intensive care unit are 5.6% and 17.0%, respectively.2 The SIRS adult criteria have been modified to produce pediatric-specific definitions. Per the 2017 Sepsis-3 guidelines, sepsis in adults is no longer based on the SIRS criteria, rather it is defined as an infection with at least one organ dysfunction. Although it may change in the future, the definition for the pediatric population remains based on the SIRS criteria due to weak evidence.3,4 Although not included in the definition of sepsis, hyperglycemia, altered mental status, and high lactate, are highly suggestive of sepsis and should be considered when evaluating a patient.Risk factors for pediatric sepsis include less than one month of age, serious injury, chronic medical problems, immunosuppression, indwelling devices, and urinary tract abnormalities. Sepsis should be in the differential diagnosis in children with persistently abnormal vital signs such as tachycardia that is often missed and attributed to other causes. Hypotension is a late finding in children; the diagnosis of shock cannot be based solely on this finding. Unlike adults, previously healthy children can compensate extremely well during hypoperfusion states and do so for relatively long periods resulting in sudden decompensation.2 Timely response to sepsis is vital to survival. Vascular access needs to be obtained, fluids administered (minimum of 60 ml/kg), broad spectrum antibiotic coverage and initiation of inotropic support in fluid refractory shock need to occur within the first hour. Hydrocortisone should be considered with catecholamine-resistant shock and if at risk for absolute adrenal insufficiency. Laboratory diagnostics such as white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) are often nonspecific. More novel tests such as lactate and procacitonin are more specific clinical adjuncts that will support diagnosis, monitor, and trend a child's progress.1,5 Key recommendations of the 2017 guidelines highlighted the importance of bundles: “recognition bundle” with trigger tools for rapid identification; “resuscitation and stabilization bundle” to increase adherence with best practice principles; and a “performance bundle” to identify gaps and barriers in the system.1 Not every child ...

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