Association Between Treatments and Short-Term Biochemical Improvements and Clinical Outcomes in Post-Severe Acute Respiratory Syndrome Coronavirus-2 Inflammatory Syndrome.

OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs. DESIGN: Multicenter observational study. SETTING: Twenty-one U.K. PICUs. PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally recommended. CONCLUSIONS: We were unable to identify any short-term benefit from any of the treatments, or treatment combinations, administered. Despite a lack of evidence, treatment guidelines for multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 have become very similar in advising step-wise treatments. Retaining clinical equipoise regarding treatment will allow clinicians to enroll children in robust clinical trials to determine the optimal treatment for this novel important condition.

Critical care scientists: Role, training and future directions.

Critical care scientists are a little known but increasingly prominent group of professionals, included in both the government-run Modernising Scientific Careers initiative and 2019 Guidelines for the Provision of Intensive Care Services. This article outlines the role of critical care scientists, their training programme and potential future directions for the role. A wider appreciation and acknowledgement of the critical care scientist's role within the multi-disciplinary team will allow critical care units to fully understand the potential benefits that may be brought to patient care and service delivery.

Caring for critically ill adults in paediatric intensive care units in England during the COVID-19 pandemic: planning, implementation and lessons for the future.

OBJECTIVE: To describe the experience of paediatric intensive care units (PICUs) in England that repurposed their units, equipment and staff to care for critically ill adults during the first wave of the COVID-19 pandemic. DESIGN: Descriptive study. SETTING: Seven PICUs in England. MAIN OUTCOME MEASURES: (1) Modelling using historical Paediatric Intensive Care Audit Network data; (2) space, staff, equipment, clinical care, communication and governance considerations during repurposing of PICUs; (3) characteristics, interventions and outcomes of adults cared for in repurposed PICUs. RESULTS: Seven English PICUs, accounting for 137 beds, repurposed their space, staff and equipment to admit critically ill adults. Neighbouring PICUs increased their bed capacity to maintain overall bed numbers for children, which was informed by historical data modelling (median 280-307 PICU beds were required in England from March to June). A total of 145 adult patients (median age 50-62 years) were cared for in repurposed PICUs (1553 bed-days). The vast majority of patients had COVID-19 (109/145, 75%); the majority required invasive ventilation (91/109, 85%). Nearly, a third of patients (42/145, 29%) underwent a tracheostomy. Renal replacement therapy was provided in 20/145 (14%) patients. Twenty adults died in PICU (14%). CONCLUSION: In a rapid and unprecedented effort during the first wave of the COVID-19 pandemic, seven PICUs in England were repurposed to care for adult patients. The success of this effort was underpinned by extensive local preparation, close collaboration with adult intensivists and careful national planning to safeguard paediatric critical care capacity.

Acute Kidney Injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Experience From PICUs Across United Kingdom.

OBJECTIVES: To study the prevalence, evolution, and clinical factors associated with acute kidney injury in children admitted to PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. DESIGN: Multicenter observational study. SETTING: Fifteen PICUs across the United Kingdom. PATIENTS: Patients admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 between March 14, 2020, and May 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deidentified data collected as part of routine clinical care were analyzed. All children were diagnosed and staged for acute kidney injury based on the level of serum creatinine above the upper limit of reference interval values according to published guidance. Severe acute kidney injury was defined as stage 2/3 acute kidney injury. Uni- and multivariable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe acute kidney injury. Over the study period, 116 patients with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 were admitted to 15 United Kingdom PICUs. Any-stage acute kidney injury occurred in 48 of 116 patients (41.4%) and severe acute kidney injury in 32 of 116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein, Pediatric Index of Mortality 3 score, vasoactive medication, and invasive mechanical ventilation were associated with severe acute kidney injury. In multivariable logistic regression, hyperferritinemia was associated with severe acute kidney injury (compared with nonsevere acute kidney injury; adjusted odds ratio 1.04; 95% CI, 1.01-1.08; p = 0.04). Severe acute kidney injury was associated with longer PICU stay (median 5 days [interquartile range, 4-7 d] vs 3 days [interquartile range, 1.5-5 d]; p < 0.001) and increased duration of invasive mechanical ventilation (median 4 days [interquartile range, 2-6 d] vs 2 days [interquartile range, 1-3 d]; p = 0.04). CONCLUSIONS: Severe acute kidney injury occurred in just over a quarter of children admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Hyperferritinemia was significantly associated with severe acute kidney injury. Severe acute kidney injury was associated with increased duration of stay and ventilation. Although short-term outcomes for acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 appear good, long-term outcomes are unknown.

Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study.

BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85-1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 µg/L to 757 µg/L), whereas the lymphocyte count increased to more than 1·0 × 109 cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.

THE IMPACT OF FIXED CONCENTRATIONS SEDATION INFUSIONS ON FLUID OVERLOAD IN CRITICALLY ILL CHILDREN.

INTRODUCTION: Fluid overload of 10% at 48 hrs (100 ml/kg additional fluid) is strongly associated with morbidity in critically ill children.1 Contributors include fluid resuscitation, acute kidney injury, and administration of intravenous drugs. Acute Kidney Injury has been observed to be more prevalent in infants.2 Drug infusions are historically prepared according to bodyweight to run at large volumes to facilitate end-of-bed calculation and administration. We report the impact of using standardised concentrations on fluid overload in critically ill children in a tertiary general PICU. METHODS: Administration of sedation infusions was prospectively documented using purposive sampling until a population-representative sample for age and weight was obtained. Infusion volumes were calculated in ml/kg/day for different weight groups - 0-5 kg, 5-20 kg and <20 kg - and compared with equivalent volumes for weight-based infusions. RESULTS: 33 patients received sedation infusions over a 5 week period. Overall drug volumes were reduced by 50.3%(41.3 to 58.7%) from 5.19 ml/kg to 2.65 ml/kg. Greatest reduction was seen in the smallest patients (total reduction 68% (16.72 ml/kg vs 5.36 ml/kg). Midazolam volumes in patients >20 kg was observed to increase (0.75 ml/kg vs. 0.95 ml/kg) but this did not have an impact on overall fluid burden. CONCLUSIONS: Weight based sedation infusions may contribute to fluid overload related morbidity, especially in infants. An infant on morphine and midazolam at standard doses (20 mcg/kg/hr and 90 mcg/kg/hr respectively) will receive 16.7 ml/kg/day (33.4% of critical fluid overload at 48 hrs) when using weight-based infusions. Using standard concentrations reduces this volume to 5.36 ml/kg/day (10.7% of critical fluid overload at 48 hrs).

Intraosseous fluid resuscitation in meningococcal disease and lower limb injury.

We set out to review the recent incidence of extravasation and compartment syndrome in children with meningococcal disease admitted to our Paediatric Intensive Care Unit (PICU) who had been resuscitated with intraosseous (IO) needles. Over a 12-month period, 18 children were admitted to PICU with meningococcal sepsis. Four of these children were resuscitated with IO needles and 2 developed serious complications as a result of extravasation and compartment syndrome. Clinical practice guidelines for children with severe sepsis advocate aggressive early fluid resuscitation therapy. We have identified extravasation and lower limb injury as a potential issue of increasing concern with appropriate aggressive IO fluid resuscitation in severe septic shock in children. Powered IO access systems such as the EZ-IO system offer advantages in terms of placement speed, accuracy and bone entry site profile at minimal extra financial cost.

Improvements in the outcome of children with meningococcal disease.

Recent years have seen a marked reduction in the mortality of children with meningococcal disease in paediatric intensive care units (PICU); the reasons for this improvement are multifactorial. The mortality rates for critically ill children overall have improved and reasons for this are probably increased centralisation of PICU services and that fewer critically ill children are now looked after on adult units. Specific treatment pathways for sepsis have improved with the publication of clinical guidelines for children and initiatives such as the Surviving Sepsis Campaign. There is a continuing need to focus on the care delivered to children before reaching PICU and to minimise the morbidity suffered by survivors of this disease.

Consensus guidelines for sustained neuromuscular blockade in critically ill children.

BACKGROUND: The United Kingdom Paediatric Intensive Care Society Sedation, Analgesia and Neuromuscular Blockade Working Group is a multidisciplinary expert panel created to produce consensus guidelines on sedation, analgesia and neuromuscular blockade in critically ill children and forward knowledge in these areas. Neuromuscular blockade is recognized as an important element in the care of the critically ill and adult clinical practice guidelines in this area have been available for several years. However, similar clinical practice guidelines have not previously been produced for the critically ill pediatric patient. METHODS: A modified Delphi technique was employed to allow the Working Group to anonymously consider draft recommendations in up to three Delphi rounds with predetermined levels of agreement. This process was supported by a total of four consensus conferences and once consensus had been achieved, a systematic review of the available literature was carried out. RESULTS: A set of consensus guidelines was produced including six key recommendations. An evaluation of the existing literature supporting these recommendations is provided. CONCLUSIONS: Multidisciplinary consensus guidelines for maintenance neuromuscular blockade in critically ill children (excluding neonates) have been successfully produced and are supported by levels of evidence. The Working Group has highlighted the paucity of high quality evidence in these important clinical areas and this emphasizes the need for further randomized clinical trials in this area.

Current United Kingdom sedation practice in pediatric intensive care.

BACKGROUND: The aim of this study was to investigate the current practice of sedation, analgesia, and neuromuscular blockade in critically ill children on pediatric intensive care units (PICUs) in the UK and identify areas that merit further study. METHODS: Data were gathered in a prospective observational study of 338 critically ill children in 20 UK PICUs. RESULTS: There is considerable variation in clinical practice. A total of 24 different sedative and analgesic agents were used during the study. The most commonly used sedative and analgesic agents were midazolam and morphine. Four different neuromuscular blockers (NMBs) were used, most commonly vecuronium. There were differences in treatment between cardiac and noncardiac children, but there were a greater number of infants and neonates in the cardiac group. NMBs were used in 30% of mechanically ventilated patients. Withdrawal symptoms were reported in 13% of ventilated patients, relatively early in their stay; weaning sedative agents ('tapering') was apparently of no benefit. The use of clonidine in this setting was noted. Physical restraints were used in 7.4%. Propofol was used but in only 2.6% of patients, all over the age of 4 years, and not exceeding 2 mgxkg(-1)xh(-1). No side effects attributable to 'propofol syndrome' were noted. CONCLUSIONS: There is considerable heterogeneity of sedation techniques. NMBs are used in a large portion of this population. Withdrawal symptoms were associated with higher doses of sedation and greater lengths of stay and were not ameliorated by withdrawing sedation gradually ('tapering').

New formulae for predicting tracheal tube length.

BACKGROUND: The aim of this study was to determine the accuracy of standard techniques for estimating oral and nasal tracheal tube length in children and to devise more accurate predictive formulae that can be used at the bedside. METHODS: Data were collected from 255 children who required tracheal intubation whilst on the Pediatric Intensive Care Unit over a period of 1 year. Age, weight, the final length of the tracheal tube and the internal diameter were documented. Patients with a tracheostomy were excluded from the study. RESULTS: Using linear regression the following formulae best predicted final tracheal tube length. For children over 1 year of age: Insertion depth (cm) for orotracheal intubation = age/2 + 13 Insertion depth (cm) for nasotracheal intubation = age/2 + 15 For children below 1 year of age: Insertion depth of orotracheal tube (cm) = weight/2 + 8 Insertion depth of nasotracheal tube (cm) = weight/2 + 9 CONCLUSIONS: Current Advanced Paediatric Life Support guidelines underestimate the appropriate tracheal tube lengths for orotracheal intubation in children over 1 year of age. Similarly, the novel weight-based formulae for tracheal tube lengths in children below the age of 1 year proved more accurate than standard reference charts. We therefore recommend that these new formulae are prospectively evaluated.

The pattern of intravenous drug administration during the transfer of critically ill children by a specialist transport team.

BACKGROUND: There are few published data on the patterns of intravenous drug administration by specialist pediatric intensive care unit (PICU) transport teams during the transfer of critically ill children between hospitals. METHODS: A retrospective review of retrieval documentation was undertaken for all patients transported by the Royal Manchester Children's Hospital PICU transport team over a period of 1 year. RESULTS: A total of 257 patients were transported during the study period, 82 patients (32%) were excluded owing to incomplete or absent documentation, leaving a sample of 175 available for analysis. Intravenous drugs were administered to 168 of these patients (96%). In total, 38 different drugs were administered. The four most commonly administered drugs were midazolam (130 patients), morphine (129 patients), atracurium (108 patients), and heparin (53 patients). Ten drugs accounted for 90% of all prescription episodes (total number of infusions and bolus doses administered), whilst 16 drugs were prescribed only once. The mean number of drugs administered per patient was 3.25 with a mean of 1.96 drug infusions and 1.29 bolus drugs administered per patient. CONCLUSIONS: A relatively small number of drugs are used frequently during the retrieval of critically ill children, but the total range of drugs that are used is large. This has implications for the rational carriage of drugs by PICU transport teams, the potential for drug errors and also for the development of advanced nurse practitioners whose prescribing-like activities may depend on the development of Patient Group Directions.

Consensus guidelines on sedation and analgesia in critically ill children.

OBJECTIVE: The United Kingdom Paediatric Intensive Care Society Sedation, Analgesia and Neuromuscular Blockade Working Group is a multi-disciplinary expert panel created to produce consensus guidelines on sedation and analgesia in critically ill children and forward knowledge in these areas. Sedation and analgesia are recognised as important areas of critical care practice and adult clinical practice guidelines in these fields remain amongst the most popular of those produced by the Society of Critical Care Medicine. However, similar clinical practice guidelines have not previously been produced for the critically ill paediatric patient. DESIGN: A modified Delphi technique was used to allow the Working Group to anonymously consider draft recommendations in three Delphi rounds with predetermined levels of agreement. This process was supported by a total of four consensus conferences. Once consensus had been reached, a systematic review of the available literature was carried out. OUTCOME: A set of consensus guidelines was produced including 20 key recommendations, 10 relating to the provision of analgesia and 10 relating to the sedation of critically ill children. An evaluation of the existing literature supporting these recommendations is provided. CONCLUSIONS: Multi-disciplinary consensus guidelines for maintenance sedation and analgesia in critically ill children have been successfully produced and are supported by levels of evidence (excluding sedation and analgesia for procedures and excluding neonates). The working group has highlighted the paucity of high-quality evidence in these important clinical areas and this emphasises the need for further randomised clinical trials in this area.

Futility and inappropriate care in pediatric intensive care: a cross-sectional survey.

BACKGROUND: Over recent years, there have been increasing concerns regarding an increase in the number of futile and inappropriate admissions to pediatric intensive care units (PICUs) in the United Kingdom (UK). METHODS: A prospective cross-sectional survey was carried out using a data collection form distributed by mail to the directors of all PICUs in the UK. Respondents were asked to give details of all patients on their unit on a specific day including age, reason for admission and any preexisting medical conditions. An assessment was made by respondents of whether the care being provided in each case was, in their opinion, appropriate, futile or inappropriate according to standard definitions. RESULTS: We received responses from 21 units (68%) who reported the details of 111 patients. Care was felt to be appropriate in 88 of these cases (79%), futile in nine cases (8%) and inappropriate in 14 cases (13%). Futile cases were most commonly admitted with respiratory failure and all had preexisting medical conditions, most commonly developmental delay. Where care was felt to be inappropriate, respiratory failure was again the most common reason for admission and all had a preexisting medical condition, most commonly cardiovascular disease. CONCLUSIONS: The care being provided in 21% of the PICU cases, described in this study, was felt to be either futile or inappropriate by the directors of those units. There is an urgent need to, accurately, establish the resource consumption associated with these patients and to establish a standard approach to futility and inappropriate care in PICU in the UK.

Exogenous surfactant in paediatric Acute Lung Injury and Acute Respiratory Distress Syndrome.

Natural pulmonary surfactant is a complex mixture of lipids and proteins with many biological functions. Surfactant is responsible for lowering the surface tension within alveoli and maintaining the functional integrity of the distal airways. In addition to this function surfactant components represent important elements of the host defence system of the lung. Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) are syndromes characterised by reduced pulmonary gas exchange due to diffuse injury to the alveolar-capillary barrier. The alveoli fill with proteinaceous fluid, and there is a marked infiltrate of acute inflammatory cells. ARDS and ALI may occur after both direct lung injury such smoke inhalation, and after indirect lung injury such as in sepsis. Qualitative and quantitative surfactant deficiencies are present in individuals suffering from ARDS and ALI, and the role of exogenous surfactant treatment in these conditions has attracted considerable interest. Most clinical studies have shown only improvements in the oxygenation of patients, but a recent study has, for the first time, demonstrated a reduction in the mortality of children with ARDS and ALI treated with exogenous surfactant. Given the differences that exist in surfactant composition, dosing schedules and the pathological processes responsible for ALI, it is clear that considerable work remains to be done in this field.

Arrhythmias associated with respiratory syncytial virus infection.

Summary A 7-week-old infant with respiratory syncytial virus infection abruptly developed complex cardiac arrhythmias in association with a low serum magnesium level. The arrhythmias were successfully treated with a single intravenous infusion of magnesium sulfate. The child was subsequently found to have a significant atrial septal defect.

The role of high-frequency oscillatory ventilation in paediatric intensive care.

Mechanical ventilation during acute respiratory failure in children is associated with development of ventilator-induced lung injury. Experimental models of mechanical ventilation that limit phasic changes in lung volumes and prevent alveolar overdistension appear to be less damaging to the lung. High-frequency oscillatory ventilation, using very small tidal volumes and relatively high end-expiratory lung volumes, provides a safe and effective means of delivering mechanical ventilatory support with the prospect of reducing the development of ventilator-induced lung injury. Despite theoretical advantages and convincing laboratory data, however, the use of high-frequency oscillatory ventilation in the paediatric population has not yet been associated with significant improvements in clinically significant outcome measures.

The use of physical restraints on paediatric intensive care units.

BACKGROUND: Physical restraints are used in critical care units in an attempt to reduce the risk of treatment interference. Their use remains controversial and there are concerns regarding the effectiveness and safety of restraint techniques. There are few data available on the prevalence of physical restraint use in Paediatric Intensive Care Units (PICU) in the UK and we have therefore conducted a cross-sectional survey to define current clinical practice. METHODS: A postal questionnaire was sent to all UK PICU with questions on the use of physical restraint techniques, including the use of splints across the joints of limbs and of securing limbs to the bed. Consent issues were also addressed. RESULTS: Of those units responding 68% reported that physical restraint techniques were used within those units. Ten units (36% of those responding) reported the use of manual holding of patients, 16 units (57% of those responding) reported the use of splints across the joints of limbs, three units reported the use of swaddling as a restraint technique while one unit secured limbs of patients to the bed. None of the units obtained written consent prior to the use of physical restraints and 53% obtained verbal consent. CONCLUSIONS: Physical restraint is a commonly used technique on PICU in the UK. There is considerable variation in clinical practice and current clinical guidelines which are available do not deal specifically with children. Prospective randomized trials would be necessary to fully investigate the role of physical restraints amongst critically ill children.