Mark J Peters

University College London | UCL · Institute of Child Health

Background High flow nasal cannula therapy (HFNC) and continuous positive airway pressure (CPAP) are two widely used modes of non-invasive respiratory support in paediatric critical care units. The FIRST-ABC randomised controlled trials (RCTs) evaluated the clinical and cost-effectiveness of HFNC compared with CPAP in two distinct critical care pop...

Objectives A conservative oxygenation strategy, targeting peripheral oxygen saturations (Sp o 2 ) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Sp o 2 greater than 94% in our recent Oxy-PICU trial. Sp o 2 monitors may overestimate arterial...

Objectives Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to eva...

Background Pulse oximetry-derived oxygen saturation (SpO2) is an estimate of true arterial oxygen saturation (SaO2). The aim of this review was to evaluate available evidence determining the effect of skin tone on the ability of pulse oximeters to accurately estimate SaO2. Methods Published literature was screened to identify clinical and non-clin...

Importance Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host respon...

Importance The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective To derive and validate novel criteria for pediatric sepsis and septic shock across different...

Background Prolonged mechanical ventilation increases the risk of mortality and morbidity. Optimising sedation and early testing for possible liberation from invasive mechanical ventilation (IMV) has been shown to reduce time on the ventilator. Alongside a multicentre trial of sedation and ventilation weaning, we conducted a mixed method process ev...

Purpose Plasma neurofilament light (NFL) is a marker of neuronal injury, associated with poor neurological outcomes in adults and neonates in a wide range of diseases. We sought to describe the associations between NFL at admission (NFL adm ) and outcomes in a heterogenous cohort of critically ill children needing unplanned admission to the pediatr...

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we...

Objective To describe comprehensively the distribution and progression of high-frequency continuous vital signs monitoring data for children during critical care transport and explore associations with patient age, diagnosis, and severity of illness. Design Retrospective cohort study using prospectively collected vital signs monitoring data linked...

Rationale: Optimal systemic oxygenation targets in pediatric critical illness are unknown. A U-shaped relationship exists between blood oxygen levels and PICU mortality. Redox stress or iatrogenic injury from intensive treatments are potential mechanisms of harm from hyperoxia. Objectives: To measure biomarkers of oxidative status in children ad...

Over the past two decades, pediatric intensive care research networks have been formed across North America, Europe, Asia, and Australia/New Zealand. The U.K. Paediatric Critical Care Society Study Group (PCCS-SG) has over a 20-year tradition of fostering collaborative research, leading to the design and successful conduct of randomized clinical tr...

Objectives Chest physiotherapy is a treatment option for mechanically ventilated children. However, there is a lack of consensus regarding its value and informal discussions suggest variation in practice. This study describes chest physiotherapy practices for mechanically ventilated children in the UK and explores clinical decision making related t...

Noninvasive respiratory support modalities such as high-flow nasal cannula (HFNC) therapy and continuous positive airway pressure (CPAP) are used frequently in pediatric critical care to support acutely ill children with respiratory failure (step-up management) and children following extubation (step-down management). Although there are several obs...

Objectives: Designing randomized trials to determine utility, dose, and timing of steroid administration in the management of critically unwell children may be difficult owing to a high proportion of patients who receive steroid as part of current care. We aimed to describe steroid use among all patients on two general PICUs. Design: Retrospecti...

This article reviews the many factors that have to be taken into account as we consider the advancement of pediatric critical care (PCC) in multiple settings across the world. The extent of PCC and the range of patients who are cared for in this environment are considered. Along with a review of the ongoing treatment and technology advances in the...

Objective Hypertension on paediatric intensive care (PICU) is associated with adverse outcomes. Management is complex; hypertension often represents a physiological adaptive response and exposure to hypertension could lead to altered pressure-flow autoregulation. International treatment consensus is to avoid rapid blood pressure (BP) reduction. Our...

Importance: The optimal first-line mode of noninvasive respiratory support for acutely ill children is not known. Objective: To evaluate the noninferiority of high-flow nasal cannula therapy (HFNC) as the first-line mode of noninvasive respiratory support for acute illness, compared with continuous positive airway pressure (CPAP), for time to li...

Importance: Diversion of cerebrospinal fluid (CSF) has been used for decades as a treatment for children with severe traumatic brain injury (TBI) and is recommended by evidenced-based guidelines. However, these recommendations are based on limited studies. Objective: To determine whether CSF diversion is associated with improved Glasgow Outcome...

Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital...

Objectives: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Spo2) t...

Background: Published reports of complex interventions in randomized controlled trials often lack sufficient detail to allow trial replication and adoption into practice. Aim: The aim of this paper is to describe our experience of using the Template for Intervention Description and Replication (TIDieR) checklist in reporting a recent trial of se...

Importance: The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known. Objective: To evaluate the noninferiority of high-flow nasal cannula (HFNC) therapy as the first-line mode of noninvasive respiratory support following extubation, compared with continuous positive airway press...

Importance: Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol. Objectives: To characterize current use of hyperosmolar agents in pediatric sev...

Introduction Acute electrolyte and acid–base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor ki...

Background Daily assessment of patient readiness for liberation from invasive mechanical ventilation can reduce the duration of ventilation. However, there is uncertainty about the effectiveness of this in a paediatric population. Objectives To determine the effect of a ventilation liberation intervention in critically ill children who are anticip...

Importance Oxygen supplementation is a cornerstone treatment in pediatric critical care. Accumulating evidence suggests that overzealous use of oxygen, leading to hyperoxia, is associated with worse outcomes compared with patients with normoxia. Objectives To evaluate the association of arterial hyperoxia with clinical outcome in critically ill ch...

Background Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and thei...

Background The coronavirus disease-19 (COVID-19) pandemic had a relatively minimal direct impact on critical illness in children compared to adults. However, children and paediatric intensive care units (PICUs) were affected indirectly. We analysed the impact of the pandemic on PICU admission patterns and patient characteristics in the UK and Irela...

Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital...

Background Acute kidney injury (AKI) is common in COVID-19. This study investigated adults hospitalised with COVID-19 and hypothesised that risk factors for AKI would include co-morbidities and non-white race. Methods A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between January 17th...

Background Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship. Methods The INHALE Random...

Objective: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. Data sources: MEDLINE, Embase, and th...

The bat connection The heterogeneity of COVID-19 makes it challenging to predict the course of infection in an individual. Upon virus infection, interferons (IFNs) generate the initial signals for cellular defenses. Knowing that defects in IFN signaling are associated with more severe COVID-19, Wickenhagen et al . used IFN-stimulated gene expressio...

The aim of this study was to appraise and summarize the effects of chest physiotherapy in mechanically ventilated children. A systematic review was completed by searching Medline, Embase, Cinahl Plus, PEDro, and Web of Science from inception to February 9, 2021. Studies investigating chest physiotherapy for mechanically ventilated children (0–18 ye...

Importance There is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit. Objective To determine if a sedation and ventilator liberation protocol intervention reduces the duration of invasive mechanical ventilation in infants and children anticipated...

Background Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians’ endorsement and uptake of these tests is crucial to maximise engagement; however, adoption may be impeded if users harbour unaddressed concerns or if device...

Background: Critical illness frequently requires the use of broad-spectrum antimicrobials to treat life-threatening infection. The resulting impact on microbiome diversity is profound, influencing gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary bile acids to secondary bile aci...

Background Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods The International Severe A...

Purpose: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. Methods: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO2 < 80%) to high-flow nasal therapy (HFNT) or low-flow ox...

Background Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evid...

Background Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. Methods In this multicentre prospective observational cohort study, the Internatio...

Background Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease,...

Objective To explore parent and staff views on the acceptability of a randomised controlled trial investigating temperature thresholds for antipyretic intervention in critically ill children with fever and infection (the FEVER trial) during a multi-phase pilot study. Design Mixed methods study with data collected at three time points: (1) before,...

Background Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECO...

Background Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. Methods We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or...

Chapter 1 begins by examining the definitions of sepsis and septic shock as subsets of the systemic inflammatory response syndrome, discusses the epidemiology of paediatric sepsis, and provides a structured approach to the assessment of a child with suspected sepsis. The evidence for and limitation of investigations, such as lactate measurement and...

Background The FIRST-ABC trial comprises of two pragmatic, multicentre, parallel groups, non-inferiority randomised clinical trials designed to evaluate the clinical non-inferiority of first-line use of high flow nasal cannula (HFNC) to continuous positive airway pressure (CPAP) in critically ill children who require non-invasive respiratory suppor...

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a novel condition that was first reported in April, 2020. We aimed to develop a national consensus management pathway for the UK to provide guidance for clinicians caring for children with PIMS-TS. A three-phase online Delphi process and virtual consensus...

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a novel condition that was first reported in April, 2020. We aimed to develop a national consensus management pathway for the UK to provide guidance for clinicians caring for children with PIMS-TS. A three-phase online Delphi process and virtual consensus...

Introduction Even though respiratory support is a common intervention in paediatric critical care, there is no randomised controlled trial (RCT) evidence regarding the effectiveness of two commonly used modes of non-invasive respiratory support (NRS), continuous positive airway pressure (CPAP) and high-flow nasal cannula therapy (HFNC). FIRST-line...

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction....

Objective: To develop a consensus management pathway for children with Paediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). Design: A three-phase online Delphi process and virtual consensus meeting sought consensus over the investigation, management and research priorities from 98 multidisciplinary partici...

Our paediatric intensive care unit (PICU) performs active surveillance for prescribing errors and detects a mean of 1.66 with an SD of 0.18 total prescription errors per occupied bed day. The primary aim of this project was to reduce the number of prescribing errors in PICU. The secondary aims were to improve the workflow in the unit and reduce the...

Objectives: Sepsis is responsible for a substantial proportion of global childhood morbidity and mortality. However, evidence demonstrates major inaccuracies in the use of the term "sepsis" in clinical practice, coding, and research. Current and previous definitions of sepsis have been developed using expert consensus but the specific criteria use...

Objectives To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. Design A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public...

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three pu...