[Advances in clinical management of neonatal sepsis]. / 新生儿败血症的临床管理进展.

Neonatal sepsis, as a significant cause of various complications and adverse outcomes in neonates, remains a serious health burden both domestically and internationally. Strategies such as antibiotic prophylaxis during delivery, the utilization of early-onset sepsis risk calculators, and quality improvement initiatives in neonatal wards are beneficial in alleviating the disease burden of neonatal sepsis. This paper provides a review of the epidemiology, risk factors, and recent advances in clinical management of neonatal sepsis.

Analysis of risk factors for death in 59 cases of critically ill neonates receiving continuous renal replacement therapy: a two-centered retrospective study.

To investigate the risk factors for death in critically ill neonates receiving continuous renal replacement therapy (CRRT). This retrospective study analyzed the clinical data of critically ill neonates receiving CRRT at two tertiary hospitals from January 2015 to December 2021. A multi-factor logistic regression analysis was performed, and the predictive value of relevant risk factors on death was verified by receiver operating characteristic (ROC) curve. A total of 59 cases of critically ill neonates were included in this study, with a mortality of 37.3%. The most common primary disease in these cases was neonatal sepsis, followed by neonatal asphyxia, and inborn errors of metabolism (IEM). Univariate analysis showed that the risk factors related to death included primary diseases; the number of organs involved in multiple organ dysfunction syndrome (MODS), neonatal critical illness scores (NCIS), and indications of CRRT; the blood lactate, blood glucose, hemoglobin, and platelet before CRRT initiation; and the incidence of bleeding or thrombosis during CRRT. Multi-factor logistic regression analysis showed that risk factors for death in critically ill neonates receiving CRRT included the occurrence of neonatal sepsis, the number of organs involved in MODS, and the NCIS. ROC curve analysis showed that the number of organs involved in MODS and NCIS had a good predictive value for death in critically ill neonates receiving CRRT, with the areas under the curve (AUC) being 0.700 and 0.810, respectively. CONCLUSION: Neonatal sepsis, the number of organs involved in MODS, and NCIS were independent risk factors for death in critically ill neonates receiving CRRT. Moreover, the number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT. WHAT IS KNOWN: • The population to which CRRT is applicable is gradually expanding from critically ill children to critically ill neonates. • The mortality of critically ill neonates receiving CRRT remains high. WHAT IS NEW: • The most common primary disease in critically ill neonates receiving CRRT was neonatal sepsis, followed by neonatal asphyxia and inborn errors of metabolism (IEM). • The number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT.

Severe neonatal COVID-19: Challenges in management and therapeutic approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may manifest as a life-threatening respiratory infection with systemic complications. Clinical manifestations among children are generally less severe than those seen in adults, but critical cases have increasingly been reported in infants less than 1 year of age. We report a severe case of neonatal COVID-19 requiring intensive care and mechanical ventilation, further complicated by a multidrug-resistant Enterobacter asburiae super-infection. Chest X-rays, lung ultrasound, and chest computed tomography revealed extensive interstitial pneumonia with multiple consolidations, associated with persistent increased work of breathing and feeding difficulties. SARS-CoV-2 RNA was detected in respiratory specimens and stools, but not in other biological samples, with a rapid clearance in stools. Serological tests demonstrated a specific SARS-CoV-2 antibody response mounted by the neonate and sustained over time. The therapeutic approach included the use of enoxaparin and steroids which may have contributed to the bacterial complication, underlying the challenges in managing neonatal COVID-19, where the balance between viral replication and immunomodulation maybe even more challenging than in older ages.

Platelet transfusions in a murine model of neonatal polymicrobial sepsis: Divergent effects on inflammation and mortality.

BACKGROUND: Platelet transfusions (PTxs) are often given to septic preterm neonates at high platelet count thresholds in an attempt to reduce bleeding risk. However, the largest randomized controlled trial (RCT) of neonatal transfusion thresholds found higher mortality and/or major bleeding in infants transfused at higher thresholds. Using a murine model, we investigated the effects of adult PTx on neonatal sepsis-induced mortality, systemic inflammation, and platelet consumption. STUDY DESIGN AND METHODS: Polymicrobial sepsis was induced via intraperitoneal injection of cecal slurry preparations (CS1, 2, 3) into P10 pups. Two hours after infection, pups were transfused with washed adult Green Flourescent Protein (GFP+) platelets or control. Weights, platelet counts, and GFP% were measured before 4 and 24 h post-infection. At 24 h, blood was collected for quantification of plasma cytokines. RESULTS: The CS batches varied in 24 h mortality (11%, 73%, and 30% in CS1, 2, and 3, respectively), due to differences in bacterial composition. PTx had differential effects on sepsis-induced mortality and systemic inflammatory cytokines, increasing both in mice infected with CS1 (low mortality) and decreasing both in mice infected with CS2 and 3. In a mathematical model of platelet kinetics, the consumption of transfused adult platelets was higher than that of endogenous neonatal platelets, regardless of CS batch. DISCUSSION: Our findings support the hypothesis that transfused adult platelets are consumed faster than endogenous neonatal platelets in sepsis and demonstrate that PTx can enhance or attenuate neonatal inflammation and mortality in a model of murine polymicrobial sepsis, depending on the composition of the inoculum and/or the severity of sepsis.

Hemodynamic dysfunction in neonatal sepsis.

Cardiovascular disturbances are a frequent occurrence in neonatal sepsis. Preterm and term infants are particularly vulnerable due to the unique features of their cardiovascular function and reserve, compared to older children and adults. The clinical manifestations of neonatal sepsis are a product of the variable inflammatory pathways involved (warm vs. cold shock physiology), developmental state of the cardiovascular system, and hormonal responses. Targeted neonatal echocardiography has played an important role in advancing our knowledge, may help delineate specific hemodynamic phenotypes in real-time, and supports an individualized physiology-based management of sepsis-associated cardiovascular dysfunction. IMPACT: Cardiovascular dysfunction is a common sequela of sepsis. This review aims to highlight the pathophysiological mechanisms involved in hemodynamic disturbance in neonatal sepsis, provide insights from targeted neonatal echocardiography-based clinical studies, and suggest its potential incorporation in day-to-day management.

Paediatric and neonatal sepsis and inflammation.

Sepsis has a huge impact on global mortality and has been declared as a priority by the World Health organisation the WHO.1 Children have a high incidence of sepsis especially in the neonatal with an estimated 3 million babies affected worldwide and mortality ranges from 11 to 19%.2 In addition, long-term neurodevelopmental outcomes are affected but this is largely unquantified. However, challenges remain in the early recognition, diagnosis and standardised management of sepsis. This series on Sepsis and inflammation in children reviews the conundrums of diagnostic criteria, biomarkers, management and future strategies to improve outcomes.

Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials.

BACKGROUND: The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered. RESULTS: Among 884 abstracts identified, 90 randomised controlled trials (RCTs) were included in this review. Only 30 manuscripts explicitly stated the primary and/or secondary outcomes. A total of 88 distinct outcomes were recorded across all 90 studies included. These were then assigned to seven different domains in line with the taxonomy for classification proposed by the COMET initiative. The most frequently reported outcome was survival with 74% (n = 67) of the studies reporting an outcome within this domain. CONCLUSIONS: This systematic review constitutes one of the initial phases in the protocol for developing a COS in neonatal sepsis. The paucity of standardised outcome reporting in neonatal sepsis hinders comparison and synthesis of data. The final phase will involve a Delphi Survey to generate a COS in neonatal sepsis by consensus recommendation. IMPACT: This systematic review identified a wide variation of outcomes reported among published RCTs on the management of neonatal sepsis. The paucity of standardised outcome reporting hinders comparison and synthesis of data and future meta-analyses with conclusive recommendations on the management of neonatal sepsis are unlikely. The final phase will involve a Delphi Survey to determine a COS by consensus recommendation with input from all relevant stakeholders.

The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis.

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Look Who's Talking: Host and Pathogen Drivers of Staphylococcus epidermidis Virulence in Neonatal Sepsis.

Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis, a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal S. epidermidis strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial S. epidermidis strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of S. epidermidis traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of S. epidermidis virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of S. epidermidis as a cause of neonatal morbidity and mortality.

Soft tissue infection as a rare cause of neonatal sepsis.

Umbilical venous and peripherally inserted central venous catheters are often used in preterm infants, but complications include late-onset catheter-associated infections. Conversely, other sites of infection have to be taken into account in the case of clinical deterioration. In this Image in Science and Medicine paper, we report on a preterm infant with a rare cause of neonatal sepsis.

Dynamics of the preterm gut microbiome in health and disease.

Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and late-onset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini-review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The host-microbiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants.

Utility of volatile organic compounds as a diagnostic tool in preterm infants.

BACKGROUND: Volatile organic compounds (VOCs) are hydrocarbons that originate within different healthy and diseased tissues. VOCs can be secreted into the circulation and then excreted in the urine and faeces. In the lungs, VOCs are locally produced and can be detected in exhaled breath. VOCs can be identified using non-invasive techniques, which make their use in preterm infants safe and desirable. METHODS: A systematic search of the literature in PubMed, Embase and Web of Science was conducted looking for VOCs techniques and diagnostic performance in preterm infants. A total of 50 articles identified with only seven papers were included in the final analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: VOCs could diagnose necrotising enterocolitis up to 4 days before a clinical diagnosis; for late onset sepsis, up to 3 days before; and for bronchopulmonary dysplasia, up to 2 weeks before. In addition to these diagnostic uses, VOCs analysis could also distinguish breastfed from formula-fed preterm neonates in the first month of life. CONCLUSION: VOCs analysis is a non-invasive tool that makes the use in preterm infants of preference. VOCs analytic techniques require more research and consensus between researchers to overcome their limitations. IMPACT: Volatile organic compounds are hydrocarbons that can separate between healthy and diseased states in preterm infants. Biomarker panels developed from volatile organic compounds are potential diagnostic tools. The non-invasive nature of acquiring volatile organic compounds markers make it desirable in the paediatric patients. Research into exact chemical components of the volatile organic compounds can inform about the pathophysiology of disease in preterm infants. More robust longitudinal studies with repeated experiments are required before volatile organic compounds can be applied in clinical practice.

Integrated community case management of childhood illness in low- and middle-income countries.

BACKGROUND: The leading causes of mortality globally in children younger than five years of age (under-fives), and particularly in the regions of sub-Saharan Africa (SSA) and Southern Asia, in 2018 were infectious diseases, including pneumonia (15%), diarrhoea (8%), malaria (5%) and newborn sepsis (7%) (UNICEF 2019). Nutrition-related factors contributed to 45% of under-five deaths (UNICEF 2019). World Health Organization (WHO) and United Nations Children's Fund (UNICEF), in collaboration with other development partners, have developed an approach - now known as integrated community case management (iCCM) - to bring treatment services for children 'closer to home'. The iCCM approach provides integrated case management services for two or more illnesses - including diarrhoea, pneumonia, malaria, severe acute malnutrition or neonatal sepsis - among under-fives at community level (i.e. outside of healthcare facilities) by lay health workers where there is limited access to health facility-based case management services (WHO/UNICEF 2012). OBJECTIVES: To assess the effects of the integrated community case management (iCCM) strategy on coverage of appropriate treatment for childhood illness by an appropriate provider, quality of care, case load or severity of illness at health facilities, mortality, adverse events and coverage of careseeking for children younger than five years of age in low- and middle-income countries. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL on 7 November 2019, Virtual Health Library on 8 November 2019, and Popline on 5 December 2018, three other databases on 22 March 2019 and two trial registers on 8 November 2019. We performed reference checking, and citation searching, and contacted study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs), cluster-RCTs, controlled before-after studies (CBAs), interrupted time series (ITS) studies and repeated measures studies comparing generic WHO/UNICEF iCCM (or local adaptation thereof) for at least two iCCM diseases with usual facility services (facility treatment services) with or without single disease community case management (CCM). We included studies reporting on coverage of appropriate treatment for childhood illness by an appropriate provider, quality of care, case load or severity of illness at health facilities, mortality, adverse events and coverage of careseeking for under-fives in low- and middle-income countries. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened abstracts, screened full texts and extracted data using a standardised data collection form adapted from the EPOC Good Practice Data Collection Form. We resolved any disagreements through discussion or, if required, we consulted a third review author not involved in the original screening. We contacted study authors for clarification or additional details when necessary. We reported risk ratios (RR) for dichotomous outcomes and hazard ratios (HR) for time to event outcomes, with 95% confidence intervals (CI), adjusted for clustering, where possible. We used estimates of effect from the primary analysis reported by the investigators, where possible. We analysed the effects of randomized trials and other study types separately. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included seven studies, of which three were cluster RCTs and four were CBAs. Six of the seven studies were in SSA and one study was in Southern Asia. The iCCM components and inputs were fairly consistent across the seven studies with notable variation for the training and deployment component (e.g. on payment of iCCM providers) and the system component (e.g. on improving information systems). When compared to usual facility services, we are uncertain of the effect of iCCM on coverage of appropriate treatment from an appropriate provider for any iCCM illness (RR 0.96, 95% CI 0.77 to 1.19; 2 CBA studies, 5898 children; very low-certainty evidence). iCCM may have little to no effect on neonatal mortality (HR 1.01, 95% 0.73 to 1.28; 2 trials, 65,209 children; low-certainty evidence). We are uncertain of the effect of iCCM on infant mortality (HR 1.02, 95% CI 0.83 to 1.26; 2 trials, 60,480 children; very low-certainty evidence) and under-five mortality (HR 1.18, 95% CI 1.01 to 1.37; 1 trial, 4729 children; very low-certainty evidence). iCCM probably increases coverage of careseeking to an appropriate provider for any iCCM illness by 68% (RR 1.68, 95% CI 1.24 to 2.27; 2 trials, 9853 children; moderate-certainty evidence). None of the studies reported quality of care, severity of illness or adverse events for this comparison. When compared to usual facility services plus CCM for malaria, we are uncertain of the effect of iCCM on coverage of appropriate treatment from an appropriate provider for any iCCM illness (very low-certainty evidence) and iCCM may have little or no effect on careseeking to an appropriate provider for any iCCM illness (RR 1.06, 95% CI 0.97 to 1.17; 1 trial, 811 children; low-certainty evidence). None of the studies reported quality of care, case load or severity of illness at health facilities, mortality or adverse events for this comparison. AUTHORS' CONCLUSIONS: iCCM probably increases coverage of careseeking to an appropriate provider for any iCCM illness. However, the evidence presented here underscores the importance of moving beyond training and deployment to valuing iCCM providers, strengthening health systems and engaging community systems.

Immunometabolic approaches to prevent, detect, and treat neonatal sepsis.

The first days of postnatal life are energetically demanding as metabolic functions change dramatically to accommodate drastic environmental and physiologic transitions after birth. It is increasingly appreciated that metabolic pathways are not only crucial for nutrition but also play important roles in regulating inflammation and the host response to infection. Neonatal susceptibility to infection is increased due to a functionally distinct immune response characterized by high reliance on innate immune mechanisms. Interactions between metabolism and the immune response are increasingly recognized, as changes in metabolic pathways drive innate immune cell function and activation and consequently host response to pathogens. Moreover, metabolites, such as acetyl-coenzyme A (acetyl-CoA) and succinate have immunoregulatory properties and serve as cofactors for enzymes involved in epigenetic reprogramming or "training" of innate immune cells after an initial infectious exposure. Highly sensitive metabolomic approaches allow us to define alterations in metabolic signatures as they change during ontogeny and as perturbed by immunization or infection, thereby linking metabolic pathways to immune cell effector functions. Characterizing the ontogeny of immunometabolism will offer new opportunities to prevent, diagnose, and treat neonatal sepsis.

Clinical Effects and Outcomes After Polymyxin B-Immobilized Fiber Column Direct Hemoperfusion Treatment for Septic Shock in Preterm Neonates.

OBJECTIVES: To compare the effectiveness and mortality of early-onset sepsis or late-onset sepsis treatments with polymyxin B-immobilized fiber column direct hemoperfusion in terms of effectiveness and mortality in preterm infants with septic shock. DESIGN: Retrospective cohort study. SETTING: Neonatal ICU within a tertiary care hospital. PATIENTS: Of 1,115 patients, 49 had blood culture-proven sepsis between January 2013 and December 2018; six and five patients with septic shock had undergone polymyxin B-immobilized fiber column direct hemoperfusion treatment for early-onset sepsis (early-onset sepsis group) and late-onset sepsis (late-onset sepsis group), respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographic characteristics of both groups were similar. The time from decision to treatment induction was significantly shorter in the early-onset sepsis group than that in the late-onset sepsis group (p = 0.008). The mortality rate after 28 days of treatment and the hospital mortality were significantly lower in the early-onset sepsis group than in the late-onset sepsis group (p = 0.026 and 0.015, respectively). The PaO2/FIO2 ratio was significantly higher in the early-onset sepsis group than in the late-onset sepsis group at the end of the treatment (p = 0.035). In addition, median arterial-to-alveolar oxygen tension ratio significantly improved from 0.19 to 0.55, and median blood pressure also significantly improved from 32.5 to 40.0 mm Hg after the treatment in the early-onset sepsis group. Interleukin-6 levels significantly decreased after treatment in the early-onset sepsis group (p = 0.037). The Pediatric Risk of Mortality III score was similar between the early-onset sepsis and late-onset sepsis groups before and after the treatment. Intraventricular hemorrhage events occurred in both groups, but with no significant differences (p = 0.175). CONCLUSIONS: Polymyxin B-immobilized fiber column direct hemoperfusion treatment for preterm infants with septic shock due to early-onset sepsis is associated with earlier hemodynamic and respiratory status improvements and with lower mortality than that due to late-onset sepsis. Early neonatal septic shock detection and polymyxin B-immobilized fiber column direct hemoperfusion induction may improve the prognosis of affected infants.

Clinical effect and safety of continuous renal replacement therapy in the treatment of neonatal sepsis-related acute kidney injury.

BACKGROUND: Sepsis is the leading cause of acute kidney injury (AKI) in the neonatal intensive care unit (NICU). The aim of the study is to explore the efficacy and security of continuous renal replacement therapy (CRRT) in the treatment of neonatal sepsis-related AKI. METHOD: Totally12 sepsis-related AKI neonates treated with CRRT were hospitalized in the NICU of Shanghai Children's Hospital between November 2012 and November 2019, and the clinical data of these 12 cases were retrospectively analyzed. Renal function, acid-base balance, electrolytes, blood pressure and hemodynamics indexes were recorded before CRRT initiation, 12/24/48 h after CRRT initiation and at the end of CRRT respectively. The efficacy of CRRT was evaluated and the clinical outcome was observed in these 12 sepsis-related AKI neonates. Repeated measurement analysis of variance was used for statistical analysis of the data. RESULT: (1) Continuous veno-venous hemodialysis filtration (CVVHDF) was used in 12 cases of sepsis-related AKI neonates. There were 6 cases with oliguria, 3 cases with fluid overload (FO), 3 cases with septic shock. The duration of CRRT was 49 ~ 110 h, average (76.2 ± 23.5) h. (2) The blood pressure (BP) of 12 sepsis -related AKI neonates could reach the normal level (40-60 mmHg) 12 h after CRRT initiation, and the normal BP level could be maintained during the CRRT treatment. After 12 h CRRT, the blood pH value increased to the normal range (7.35 ~ 7.45). After 12 h CRRT treatment, the oxygenation index of 12sepsis-related AKI neonates could reach 200 mmHg. After 24 h CRRT treatment, it could rise to more than 300 mmHg. Serum potassium, serum urea nitrogen and serum creatinine levels decreased significantly 12 h after CRRT initiation, and reached the normal range 24 h after CRRT initiation. The urine volume significantly increased 24 h after CRRT initiation. (3) Venous catheterization was performed successfully in all sepsis-related AKI neonates. We observed 2 cases of thrombocytopenia, 1 case of obstruction and 1 case of hypotension in the course of CRRT. There were no complications such as hypothermia, hemorrhage, thrombosis and infection.11 neonates were cured and discharged. One neonate was treated with CRRT and passed through the oliguria stage of AKI, but died after the parents gave up the treatment. CONCLUSIONS: It is safe and effective to treat neonatal sepsis-related AKI with CRRT, which should be an effective measure for the treatment of sepsis-related AKI neonates.

Therapeutic Plasma Exchange in Neonatal Septic Shock: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to examine the use of therapeutic plasma exchange (TPE) as adjunctive therapy in neonatal septic shock. STUDY DESIGN: This retrospective cohort study was performed on a convenience sample of neonates in a quaternary children's hospital between January 2018 and February 2019. RESULTS: We identified three neonates with septic shock who received TPE. Two neonates had adenovirus sepsis, and one had group B streptococcal sepsis. All neonates were on extracorporeal life support (ECLS) when TPE was started. The median duration of TPE was 6 days (interquartile range [IQR]: 3-15), with a median of four cycles (IQR: 3-5). Lactate levels decreased significantly after TPE (median before TPE: 5.4 mmol/L [IQR: 2.4-6.1] vs. median after TPE: 1.2 mmol/L [IQR: 1.0-5.8]; p < 0.001). Platelet levels did not change (median before TPE: 73,000/mm3 [IQR: 49,000-100,000] vs. median after TPE: 80,000/mm3 (IQR: 62,000-108,000); p = 0.2). Organ failure indices improved after TPE in two of the three neonates. Hypocalcemia was seen in all cases despite prophylactic calcium infusions. One neonate died, and two survived to ICU discharge. CONCLUSION: TPE can be safely performed in neonates with septic shock. TPE may have a role as an adjunctive therapy in neonates with septic shock requiring ECLS.

Bhutan's First Emergency Air Medical Retrieval Service: The First Year of Operations.

OBJECTIVE: The Bhutan Emergency Aeromedical Retrieval (BEAR) Team is the only helicopter emergency medical service in Bhutan. This study was performed to review the clinical cases cared for by the BEAR Team, ascertain the types of interventions that were performed, and determine the outcomes of patients evacuated in its first year of operations. METHODS: This is a retrospective observational study in which medical evacuations performed in the first year of operations were analyzed. The number of airlifts activated during the study period determined the sample size (171). Data were obtained from case logs and trip sheets. RESULTS: The BEAR Team provided services to all regions of the country in its first year. The overall survival rate was 73.1%. The most common intervention required was securing a definitive airway (n = 24). The top 3 conditions requiring air medical retrieval were sepsis, acute mountain sickness, and trauma. CONCLUSION: Helicopter emergency medical services are known to decrease the time to definitive treatment. This is particularly pertinent in Bhutan, given the scattered population distribution, long transport times, and distribution of medical resources and specialty care. This study is the first of its kind in Bhutan, and this can pave way to conduct more studies involving patients transported by air ambulance.

Use of a Modified Early-Onset Sepsis Risk Calculator for Neonates Exposed to Chorioamnionitis.

OBJECTIVE: To validate the recently modified Kaiser Permanente early-onset sepsis (EOS) calculator with a higher baseline incidence in chorioamnionitis exposed neonates. STUDY DESIGN: This is a retrospective study of chorioamnionitis-exposed neonates born at ≥35 weeks of gestation with a known EOS incidence of 4.3/1000. The risk and management categories were calculated using the calculator with an incidence of 4/1000. The results were compared with a previous analysis of the same cohort that used an EOS incidence of 0.5/1000. RESULTS: In our sample, the EOS calculator recommends at least a blood culture in 834 of 896 (93.1%) and empiric antibiotics in 533 of 896 (59.5%) chorioamnionitis-exposed neonates when using an EOS incidence of 4/1000. This captures 5 of 5 neonates (100%) with EOS. When using a baseline EOS incidence of 0.5/1000, the calculator recommends at least a blood culture in only 289 of 896 (32.2%) and empiric antibiotics in only 209 of 896 (23.3%) neonates, but fails to recommend empiric antibiotics in 2 of 5 neonates with EOS (40%). CONCLUSIONS: When using an EOS risk of 4 of 1000 in infants exposed to mothers with chorioamnionitis, the EOS calculator has the ability to capture an increased number of neonates with culture-positive EOS. However, this change also leads to nearly a 3-fold increase in the use of empiric antibiotics and an evaluation with blood culture in almost all infants born to mothers with chorioamnionitis.

Increased surfactant protein-D levels in the airways of preterm neonates with sepsis indicated responses to infectious challenges.

AIM: Sepsis is multifactorial and potentially devastating for preterm neonates. Changes in surfactant protein-D (SP-D), phosphatidylcholine (PC) and PC molecular species during infection may indicate innate immunity or inflammation during sepsis. We aimed to compare these important pulmonary molecules in ventilated neonates without or with sepsis. METHODS: Endotracheal aspirates were collected from preterm neonates born at 23-35 weeks and admitted to the neonatal intensive care unit at the John Radcliffe Hospital, Oxford, UK, from October 2000 to March 2002. Samples were collected at one day to 30 days and analysed for SP-D, total PC and PC molecular species concentrations using enzyme-linked immunosorbent assay and mass spectrometry. RESULTS: We found that 8/54 (14.8%) neonates developed sepsis. SP-D (p < 0.0001), mono- and di-unsaturated PC were significantly increased (p = 0.05), and polyunsaturated PC was significantly decreased (p < 0.01) during sepsis compared to controls. SP-D:PC ratios were significantly increased during sepsis (p < 0.001), and SP-D concentrations were directly related to gestational age in neonates with sepsis (r2  = 0.389, p < 0.01). CONCLUSION: Increased SP-D levels and changes in PC molecular species during sepsis were consistent with direct or indirect pulmonary inflammatory processes. Very preterm neonates we able to mount an acute inflammatory innate immune response to infectious challenges, despite low levels of surfactant proteins at birth.