Degradation of the Endothelial Glycocalyx Contributes to Metabolic Acidosis in Children Following Cardiopulmonary Bypass Surgery.

OBJECTIVES: Cardiopulmonary bypass surgery is complicated by metabolic acidosis, microvascular dysfunction, and capillary leak. The glycocalyx-a layer of proteins and sugars lining the vascular endothelium-is degraded during cardiopulmonary bypass. We aimed to describe the kinetics of glycocalyx degradation during and following cardiopulmonary bypass. We hypothesized that cleavage of negatively charged fragments of the glycocalyx would directly induce metabolic acidosis through changes in the strong ion gap (defined using Stewart's physicochemical approach to acid-base chemistry). We also investigated whether glycocalyx degradation was associated with failure of endothelial function and cardiovascular dysfunction. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed surgical/medical PICU. PATIENTS: Twenty-seven term infants and children requiring cardiopulmonary bypass surgery for the correction/palliation of congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recruited 27 patients, 5 days to 57 months old. We prospectively sampled plasma prior to, during, and following cardiopulmonary bypass at predefined time points. We measured plasma concentrations of interleukin-6 (inflammatory marker), heparan sulfate (negatively charged glycocalyx glycosaminoglycan), and syndecan-1 (neutrally charged glycocalyx protein). We defined the following outcome measures: metabolic acidosis (strong ion gap), renal dysfunction (fold change in creatinine), capillary leak (fluid bolus volume), cardiovascular dysfunction (Vasoactive Inotropic Score), and length of ventilation. In linear regression models, maximum measured heparan sulfate concentration (negatively charged) was associated with metabolic acidosis (p = 0.016), renal dysfunction (p = 0.009), and length of ventilation (p = 0.047). In contrast, maximum measured syndecan-1 concentration (neutrally charged) was not associated with these clinical endpoints (p > 0.30 for all). CONCLUSIONS: Our data show that metabolic acidosis (increased strong ion gap) is associated with plasma concentration of heparan sulfate, a negatively charged glycosaminoglycan cleaved from the endothelial glycocalyx during cardiopulmonary bypass. In addition, cleavage of heparan sulfate was associated with renal dysfunction, capillary leak, and global markers of cardiovascular dysfunction. These data highlight the importance of designing translational therapies to protect the glycocalyx in cardiopulmonary bypass.

Cortisol Response in Children After Second Cardiopulmonary Bypass.

A surge in cortisol levels is seen after surgery with cardiopulmonary bypass (CPB). Based on evidence of attenuation of the cortisol response to repeated stress in other settings, we hypothesized that the magnitude of cortisol increase in children after a second exposure to CPB would be reduced. Serial cortisol levels were measured at three time points after each CPB: immediately (day 0), on the first morning (day 1), and second morning (day 2). Forty-six children underwent two surgeries with CPB during the study period. The mean age (standard deviation) at first and second surgery was 3.5 (6.3) months and 10.4 (9.9) months, respectively. Cortisol levels at the first surgery were 109 (105) µg/dl, 29 (62) µg/dl, and 17 (12) µg/dl on day 0, 1, and 2, respectively; similarly at second surgery, it was 61 (57) µg/dl on day 0 to 20 (16) µg/dl and 11 (10) µg/dl on day 1 and 2, respectively. After log-transformation and adjusting for time interval between surgeries, cortisol levels at the second surgery were lower by 42% on day 0 (p = 0.02), and 46% lower on day 2 (p = 0.02). A second exposure to CPB in children with congenital heart disease is associated with an attenuated cortisol release.

The Total Inotrope Exposure Score: an extension of the Vasoactive Inotrope Score as a predictor of adverse outcomes after paediatric cardiac surgery.

OBJECTIVE: The aim of the present study was to explore and compare the association between a new vasoactive score - the Total Inotrope Exposure Score - and outcome and the established Vasoactive Inotrope Score in children undergoing cardiac surgery with cardiopulmonary bypass DESIGN: The present study was a single-centre, retrospective study. SETTING: The study was carried out at a 21-bed cardiovascular ICU in a Tertiary Children's Hospital between September, 2010 and May, 2011 METHODS: The Total Inotrope Exposure Score is a new vasoactive score that brings together cumulative vasoactive drug exposure and incorporates dose adjustments over time. The performance of these scores - average, maximum Vasoactive Inotrope Score at 24 and 48 hours, and Total Inotrope Exposure Score - to predict primary clinical outcomes - either death, cardiopulmonary resuscitation, or extra-corporeal membrane oxygenation before hospital discharge - and secondary outcomes - length of invasive mechanical ventilation, length of ICU stay, and hospital stay - was calculated. Main results The study cohort included 167 children under 18 years of age, with 37 (22.2%) neonates and 65 (41.3%) infants aged between 1 month and 1 year. The Total Inotrope Exposure Score best predicted the primary outcome (six of 167 cases) with an unadjusted odds ratio for a poor outcome of 42 (4.8, 369.6). Although the area under curve was higher than other scores, this difference did not reach statistical significance. The Total Inotrope Exposure Score best predicted prolonged invasive mechanical ventilation, length of ICU stay, and hospital stay as compared with the other scores. CONCLUSION: The Total Inotrope Exposure Score appears to have a good association with poor postoperative outcomes and warrants prospective validation across larger numbers of patients across institutions.

Serum cortisol and early postoperative outcome after stage-1 palliation for hypoplastic left heart syndrome.

OBJECTIVES: The postoperative cortisol profile and its association with early outcomes are poorly understood in neonates undergoing surgery for complex congenital heart disease. We investigated the postoperative profile of cortisol and its relationship with the clinical course in a cohort of newborns after stage-1 palliation for hypoplastic left heart syndrome. DESIGN: Prospective observational study. SETTING: Pediatric cardiovascular ICU at a tertiary children's hospital. SUBJECTS: Twenty-three neonates after stage-1 palliation for hypoplastic left heart syndrome between 2009 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three serial measurements of total serum cortisol after surgery. The first measurement was taken immediately after surgery and the second and third-on the first and second postoperative mornings. The median weight of the infants was 3.0 kg (2.7-3.4 kg), and the age at surgery was 7 days (6-9 d). The median (25th-75th percentile) cortisol levels at admission, day 1, and day 2 were 96.2 µg/dL (51.1-112 µg/dL), 17.3 µg/dL (9.7-25.1 µg/dL), and 10 µg/dL (6.5-17 µg/dL), respectively (p < 0.0001 between admission and day 1). Higher cortisol was associated with greater morbidity, including the need for preoperative ventilation, increased total duration of ventilation, duration of inotropic support, and hospital length of stay. CONCLUSIONS: Cortisol levels fell significantly over the first 24 hours after stage-1 palliation for hypoplastic left heart syndrome. A higher postoperative cortisol was associated with increased postoperative morbidity, which warrants further investigation.

An eighteen-year review of intensive care requirements for paediatric burns in a regional burns service.

INTRODUCTION: Advances in burns management have reduced mortality. Consequently, efficient resource management plays an increasingly important role in improving paediatric burns care. This study aims to assess the support requirements and outcomes of paediatric burns patients admitted to a burns centre intensive care unit in comparison to established benchmarks in burns care. METHOD: A retrospective review of burns patients under the age of 16 years old, admitted to a regional burns service intensive care unit between March 1998 and March 2016 was conducted. RESULTS: Our analysis included 234 patients, with the percentage of TBSA affected by burn injury ranging from 1.5% to 95.0%. The median (IQR) %TBSA was 20.0% (11.0-30.0), and the observed mortality rate was 2.6% (6/234). The median (IQR) length of stay was 0.7 days/%TBSA burn (0.4-1.2), 17.9% (41/229) required circulatory support and 2.6% (6/234) required renal replacement. Mortality correlated with smoke inhalation injury (P < 0.001), %TBSA burn (P = 0.049) and complications (P = 0.004) including infections (P = 0.013). CONCLUSIONS: Among children with burn injuries who require intensive care, the presence of inhalational injury and the diagnosis of infection are positively correlated with mortality. Understanding the requirements for organ support can facilitate a more effective allocation of resources within a burns service.

Research Priorities for Pediatric Intensive Care Nutrition Within the United Kingdom: A National Institute of Health Research James Lind Alliance Priority Setting Partnership.

OBJECTIVES: To determine research priorities in PICU nutrition, which represent the shared priorities of patients, parents, carers, and PICU healthcare professionals within the United Kingdom. DESIGN: A national multiphase priority setting methodology in partnership with the James Lind Alliance delivered over 16 months (June 2020-September 2021). Part 1: a national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. Part 2: summarizing and evidence-checking the submitted uncertainties. Part 3: interim prioritization survey. Part 4: consensus workshop. SETTING: PICU. PARTICIPANTS: Patients, parents, and carers of patients who had been admitted to PICU, and PICU healthcare professionals involved in the treatment of these patients within the United Kingdom. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. In the first survey, 165 topic ideas were suggested (12% by parents/carers and 88% by PICU healthcare professionals). These were categorized into 57 summary questions. The existing evidence was searched to ensure that the proposed summary questions had not already been answered. Forty were judged to be true uncertainties following a systematic literature review. These 40 uncertainties were grouped into eight themes for the second interim survey, which asked respondents to prioritize their top research questions. One hundred and forty participants contributed to this second interim survey. A final shortlist of 25 questions was derived, with the top 18 questions taken to a multistakeholder workshop where a consensus was reached on the top 10 priorities. CONCLUSIONS: This research identified important research gaps in the management of patients in PICU. Areas that need to be addressed as a priority include energy requirements in ventilated neonates, nutritional supplementation of probiotics to manage and prevent sepsis, the impact of postintensive care syndrome on nutrition and growth, and when to commence parenteral (IV) nutrition. The challenge now is to refine and deliver answers to these research priorities.

Macrolide and fluoroquinolone mediated cardiac arrhythmias: clinical considerations and comprehensive review.

While there is evidence for cardiac arrhythmias associated with macrolide and fluoroquinolone antibiotics, there is still debate among health care providers as to whether this risk of arrhythmia is overstated. A joint panel of the US Food and Drug Administration suggested that macrolide and fluoroquinolone labels need much stronger warnings regarding the possible serious adverse cardiac effects associated with these antibiotics, especially since they are so widely prescribed. And while health care providers may differ on the pertinence of the cardiac risks associated with antibiotic use, they can undoubtedly minimize the cardiac effects that are associated with these antibiotics by paying attention to the cardiac risk factors and drug history associated with the patient. Relevant studies for our review were identified from a PubMed search using keywords and combined word searches involving macrolides, fluoroquinolones, and cardiac arrhythmias. We attempted to include as many recent (>2015) articles as possible. We included case reports, randomized, controlled trials, observational studies, case-control studies, systematic reviews, and retrospective studies. Underlying cardiac issues can predispose patients to harmful cardiac side effects that can be exacerbated in the presence of antibiotics. The health care provider should rule out any risk factor associated with antibiotic-induced cardiac arrhythmia in the event that a patient does need a macrolide or fluoroquinolone antibiotic. Rigorous patient evaluation and a detailed patient history, including short and long term medication use, is the likely key to reducing any risk of cardiac arrhythmias associated with macrolides and fluoroquinolones. Clinicians should be cautious when prescribing macrolide and fluoroquinolone medications to patients with risk factors that may lead to antibiotic-induced cardiac arrhythmias, including a slow heart rate and those that are taking medications to treat arrhythmias.

Patient characteristics and severity of human rhinovirus infections in children.

BACKGROUND: It is increasingly recognized that human rhinoviruses (HRV) can be associated with severe infections. However, conflicting results have been reported on the relative prevalence and severity of the three HRV species. OBJECTIVES: The relative prevalence and clinical characteristics of HRV-A, B and C, in children attending a South London teaching hospital were investigated retrospectively. STUDY DESIGN: Children aged<16 years with episodes of respiratory tract infections and detectable entero/rhinovirus RNA in respiratory samples between November 2009 and December 2010 were investigated. Retrospective case review was performed and patients' characteristics recorded. RESULTS: Entero/rhinoviruses were the commonest viral pathogens (498/2316; 21.5%). Amongst 204 infection episodes associated with entero/rhinovirus, 167 were typed HRV, HRV-C was the most prevalent (99/167, 59.3%) followed by HRV-A (60/167; 35.9%) and HRV-B (8/167, 4.8%). The severity spectrum of HRV-A and HRV-C infections were similar and affected all parts of the respiratory tract. Co-pathogens were observed in 54 (26.5%) episodes. Severity was increased in patients with non-viral co-pathogens and those with an underlying respiratory condition. Univariate and multiple regression analyses of potential prognostic variables including age, co-pathogens and underlying respiratory illnesses showed that mono-infection with HRV-C, as compared with other HRV species, was associated with more severe disease in young children<3 years. CONCLUSIONS: HRV-C was the most prevalent species and on its own was associated with severe disease in children<3 years. The association between infection with HRV species and clinical presentation is complex and affected by many confounding factors.

Abdominal distension: an important feature in human parechovirus infection.

A total of 8 infants presenting with sepsis-like illness were diagnosed to have human parechovirus (HPeV) infection; of which, 5 had abdominal distension and 6 had an erythematous rash. A combination of abdominal distension and erythematous rash was observed in 4 infants. The abdominal symptoms can be very prominent and signs could be confused with acute surgical conditions. Although fever and central nervous symptoms are important features, a red rash with abdominal distension and a low C-reactive protein value and lymphocyte count can be clues to recognize this infection.

Rickets and tracheobronchomalacia.

Rickets is increasingly encountered in practice, even in the Western world. One recent publication reports an overall incidence of 7.5 per 100 000 children. Respiratory infections are well known to be associated with rickets. We present a case of rickets with severe respiratory complications. Tracheobronchomalacia was detected on bronchoscopy. We believe that tracheobronchomalacia may be a hitherto unrecognised finding in rickets and may need to be investigated further.