In-vivo-and in-vitro evaluation of the 5 French neonatal gastric tonometer

Introduction - Gastrointestinal tonometry has been widely used in adult practice for the early detection of shock and multi-organ failure. Its application in paediatrics has been limited by unsuitably large tonometers and doubt about the accuracy of measurements when saline is used as a tonometric fluid / vehicle for carbon dioxide (CO₂) equilibration. Objective - To evaluate the accuracy and reliability of the newly developed saline 5 French (5F) neonatal gastric tonometer. Study Design - (a) Direct in-vivo comparison of the 5F 0.9%saline tonometer (NST) with the recirculating gas tonometer (RGT) [the current reference standard in adult practice] in 10 Paediatric intensive care unit (PICU) patients, measuring tonometric PCO₂ (PtCO₂) and gastric intramucosal PCO₂ (PiCO₂). (b) In-vivo comparison of PiCO₂ measurements from two 5F tonometers in 10 PICU patients in unfed and fed state. (c) In-vitro comparison of reference PCO₂ to PtCO₂ values obtained using 0.9%saline and phosphate buffered saline in SF tonometers, and the RGT. Results - (a) Comparing the SF NST to RGT in 50 paired simultaneous measurements over PtCO₂ range 3.0 - 9.7kPa, the mean bias was -1.44kPa; limits of agreements (LOA) ±1.45kPa. The mean values of PtCO₂- derived gastric intramucosal pH (pHi) and PiCO₂-PaCO₂ difference differed significantly by -.11 and + 1.1kPa respectively (p<0.0001). (b) 100 paired 5F NST measurements (50 fed/ 50 unfed) over PtCO₂ range 2.48-11.1kPa were assessed. No significant difference was observed in PtCO₂: mean difference (standard deviation) - unfed 0.05kPa (0.36) (p=0.36); fed 0.05kPa (0.42) (p=0.43). (c) 20 consecutive measurements of PtCO₂ were obtained from the 5F NST, 5F phosphate buffered saline tonometer (PBST) and RGT at constant reference PCOi's of 2.5, 5.0, 7.5, 10.0kPa. The 5F NST underestimated the reference PCO₂ by a mean bias of 58% (LOA ±20%); the 5F PBST by 6% (LOA ±26%); while the RGT performed best with a mean bias of 5.7% and tight LOA ±1.5%. Conclusion - There are inherent problems in the methodology of the saline tonometry utilised in the 5F neonatal gastric tonometer. The use of the saline SF neonatal gastric tonometer to monitor gut perfusion in neonates and children should be interpreted with caution. Recirculating gas tonometry is the most accurate method of tonometry studied

Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: A multicentre randomized clinical pilot trial

Background: Fever improves pathogen control at a significant metabolic cost. No randomized clinical trials (RCT) have compared fever treatment thresholds in critically ill children. We performed a pilot RCT to determine whether a definitive trial of a permissive approach to fever in comparison to current restrictive practice is feasible in critically ill children with suspected infection. Methods: An open, parallel-group pilot RCT with embedded mixed methods perspectives study in four UK paediatric intensive care units (PICUs) and associated retrieval services. Participants were emergency PICU admissions aged > 28 days to < 16 years receiving respiratory support and supplemental oxygen. Subjects were randomly assigned to permissive (antipyretic interventions only at ≥ 39.5 °C) or restrictive groups (antipyretic interventions at ≥ 37.5 °C) whilst on respiratory support. Parents were invited to complete a questionnaire or take part in an interview. Focus groups were conducted with staff at each unit. Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between group separation of temperature and safety. Results: One hundred thirty-eight children met eligibility criteria of whom 100 (72%) were randomized (11.1 patients per month per site) without prior consent (RWPC). Consent to continue in the trial was obtained in 87 cases (87%). The mean maximum temperature (95% confidence interval) over the first 48 h was 38.4 °C (38.2-38.6) in the restrictive group and 38.8 °C (38.6-39.1) in the permissive group, a mean difference of 0.5 °C (0.2-0.8). Protocol deviations were observed in 6.8% (99/1438) of 6-h time periods and largely related to patient comfort in the recovery phase. Length of stay, duration of organ support and mortality were similar between groups. No pre-specified serious adverse events occurred. Staff (n = 48) and parents (n = 60) were supportive of the trial, including RWPC. Suggestions were made to only include invasively ventilated children for the duration of intubation. Conclusion: Uncertainty around the optimal fever threshold for antipyretic intervention is relevant to many emergency PICU admissions. A more permissive approach was associated with a modest increase in mean maximum temperature. A definitive trial should focus on the most seriously ill cases in whom antipyretics are rarely used for their analgesic effects alone. Trial registration: ISRCTN16022198. Registered on 14 August 2017

Which outcomes should be used in future bronchiolitis trials? Developing a bronchiolitis core outcome set using a systematic review, Delphi survey and a consensus workshop

Objectives The objective of this study was to develop a core outcome set (COS) for use in future clinical trials in bronchiolitis. We wanted to find out which outcomes are important to healthcare professionals (HCPs) and to parents and which outcomes should be prioritised for use in future clinical trials.Design and setting The study used a systematic review, workshops and interviews, a Delphi survey and a final consensus workshop.Results Thirteen parents and 45 HCPs took part in 5 workshops; 15 other parents were also separately interviewed. Fifty-six items were identified from the systematic review, workshops and interviews. Rounds one and two of the Delphi survey involved 299 and 194 participants, respectively. Sixteen outcomes met the criteria for inclusion within the COS. The consensus meeting was attended by 10 participants, with representation from all three stakeholder groups. Nine outcomes were added, totalling 25 outcomes to be included in the COS.Conclusion We have developed the first parent and HCP consensus on a COS for bronchiolitis in a hospital setting. The use of this COS will ensure outcomes in future bronchiolitis trials are important and relevant, and will enable the trial results to be compared and combined

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries

Death by acid rain: VAP or EXIT?

Ventilator-associated pneumonia (VAP) is a new (nosocomial) lower respiratory tract infection diagnosed in mechanically ventilated patients 48 or more hours after intubation. There is no gold standard for establishing the diagnosis and its pathogenesis is iatrogenic and multifactorial. Gastro-oesophageal reflux is common in mechanically ventilated children, but its role in VAP remains speculative. VAP is associated with increased mortality and morbidity, prolonged duration of ventilation and hospital stay, and escalated costs of hospitalisation. VAP 'bundles' are championed as the antidote

Transaminase levels reflect disease severity in children ventilated for respiratory syncytial virus (RSV) bronchiolitis

Abstract Bronchiolitis, often caused by respiratory syncytial virus (RSV), is the commonest cause of hospitalisation in infancy. Serum transaminases are sometimes raised in children with bronchiolitis. We tested the hypothesis that raised transaminases are associated with increased disease severity in children ventilated for bronchiolitis. Prospective observational cohort study of mechanically ventilated children with community-acquired RSV bronchiolitis. Alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured daily. Children with normal transaminases were compared with those with elevated levels. Over 11 consecutive winters, 556 children with RSV bronchiolitis were mechanically ventilated – 226 had comorbidities and therefore excluded; 313 of remaining 330 were under 2 years age; 305 had early transaminase measurements. 57/305 (19%) had elevated transaminase (AST and/or ALT) levels. For the first time we show that duration of ventilation and length of admission were both significantly longer, and paediatric index of mortality and C-reactive protein higher, in those with elevated AST levels on admission (but not those with elevated ALT levels). Furthermore, transaminase elevations were transient, generally having normalised by seven days following admission. RSV bronchiolitis was more severe in children with early elevated AST levels and could be used early in the illness as a predictor for disease severity