Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to F io2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/F io2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Recommendations on the Management of Interhospital Transport of Pediatric Patients With Mediastinal Mass.

PURPOSE: Children with mediastinal masses often present with insidious symptoms to nonspecialist centers and require interhospital transport to oncology centers for definitive care. We evaluated clinical characteristics and patient outcomes and proposed a management protocol. MATERIALS AND METHODS: This is a retrospective review of all children with mediastinal mass at the pediatric intensive care unit of the Hong Kong Children's Hospital between April 2019 and March 2020. RESULTS: Ten children with a median age of 14.5 years (interquartile range, 9.3-17.0 years) were included. Leukemia and lymphoma accounted for the majority of cases (n = 6, 60%). Nearly all patients (n = 9, 90%) required interhospital transport before definitive treatment could be instituted. There were no deaths, but 2 patients were transported with significant respiratory compromise. Among patients requiring more than 1 interhospital transport, there was a higher incidence of shortness of breath (100% vs 40%; odds ratio, 33; P = 0.048) and orthopnea (80% vs 0%; odds ratio, 33; P = 0.048), whereas none had a neck mass (0% vs 80%; odds ratio, 0.03; P = 0.048). CONCLUSIONS: Children with mediastinal mass are at risk of life-threatening cardiorespiratory compromise. Pretransport assessment, planning, and stabilization along with clear management plans for deterioration during transport are crucial especially for patients who are symptomatic at time of presentation, to reduce risks associated with delays in arriving at the specialist point of care for definitive treatment.

Clinical Characteristics and Outcomes of Acute Childhood Encephalopathy in a Tertiary Pediatric Intensive Care Unit.

AIM: Childhood encephalopathy comprises a wide range of etiologies with distinctive distribution in different age groups. We reviewed the pattern of encephalopathy admitted to the pediatric intensive care unit (PICU) of a tertiary children's hospital. METHODS: We reviewed the medical records and reported the etiologies, clinical features, and outcomes of children with encephalopathy. RESULTS: Twenty-four admissions to the PICU between April 2019 and May 2020 were reviewed. The median (interquartile range) age was 10.0 (14.7) years and 62.5% were boys. Confusion (66.7%) was the most common presentation. Adverse effects related to medications (33.3%) and metabolic disease (20.8%) were predominant causes of encephalopathies in our study cohort. Methotrexate was responsible for most of the medication-associated encephalopathy (37.5%), whereas Leigh syndrome, pyruvate dehydrogenase deficiency and Wernicke's encephalopathy accounted for those with metabolic disease. The median Glasgow Coma Scale (GCS) on admission was 12.5 (9.0). Antimicrobials (95.8%) and antiepileptic drugs (60.9%) were the most frequently given treatment. Children aged 2 years or younger were all boys (P = 0.022) and had a higher proportion of primary metabolic disease (P = 0.04). Intoxication or drug reaction only occurred in older children. The mortality was 8.3%, and over half of the survivors had residual neurological disability upon PICU discharge. Primary metabolic disease (P = 0.002), mechanical ventilation (P = 0.019), failure to regain GCS back to baseline level (P = 0.009), and abnormal cognitive function on admission (P = 0.03) were associated with cerebral function impairment on PICU discharge. CONCLUSIONS: Primary metabolic encephalopathy was prevalent in younger children, whereas drug-induced toxic encephalopathy was common among older oncology patients. Survivors have significant neurologic morbidity. Failure to regain baseline GCS was a poor prognostic factor for neurological outcomes.

Diagnostic Yield of Bronchoalveolar Lavage in Immunocompromised Children.

Results from early studies in the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised adults and children were variable. This prospective study aimed to determine the diagnostic yield of BALs in immunocompromised children over the first 18 months of service at a newly established children's hospital. Relationship between BAL results and changes in antimicrobial management was also studied. Twenty-one bronchoscopic BALs were performed on 18 children; 14 BALs (66.7%) yielded at least 1 pathogen and 7 (33.3%) yielded no pathogen. Two pathogens were found in 2 samples, and 1 pathogen was identified in 12 samples. Bacteria (n = 7 patients), viruses (n = 8 patients) and fungus (Pneumocycstis jirovecii in one patient) were yielded. Of the 21 BALs, 8 (38.1%) were associated with changes in antimicrobial management (Fisher's exact test, p = 0.018). No significant side effects such as pneumothorax or pulmonary hemorrhages were observed in this series. In conclusion, BAL in immunocompromised children is rewarding and has potential to impact on antimicrobial management.

Myocardial oedema in an 8-year-old Chinese boy with Idiopathic systemic capillary leak syndrome.

BACKGROUND: Idiopathic systemic capillary leak syndrome (ISCLS) is rare, and there has been about 32 cases reported in children worldwide since this disorder was first described in 1960. Clinical guidelines on the management approach stemming from robust scientific evidence are lacking. This case report presents the first reported paediatric case of severe ISCLS with significant myocardial oedema and emphasizes this disease's impact on a child's cardiac function. CASE PRESENTATION: A Chinese boy had his first attack of severe hypovolaemic shock that responded to fluid resuscitation when he was 6 years of age. His second attack developed at 8 years of age. He was then transferred to our cardiac unit for refractory hypotensive shock. The patient's echocardiogram revealed ventricular wall thickening with significant cardiac dysfunction requiring extracorporeal membrane oxygenation support. Subsequently, he made a full recovery, including his myocardial wall thickness and function. The echocardiographic findings suggested myocardial oedema that was transient in nature. Clinical and laboratory investigation from both episodes were compatible with ISCLS. CONCLUSION: ISCLS is rare, and therefore there is only a limited understanding on the pathophysiology of this disorder. The current treatment approach is based on a few case reports and series. During the acute phase, optimal supportive management is paramount. Our case highlights the importance of early recognition and consideration for extracorporeal membrane oxygenation support in patients with a life-threatening presentation, as it was lifesaving for this child who suffered myocardial oedema and ventricular dysfunction.

Review of Issues and Challenges of Practicing Emergency Medicine Above 30,000-Feet Altitude: 2 Anonymized Cases.

We present 2 anonymized cases to identify issues and challenges associated with long-haul in-flight medical emergencies. The first case involved a middle-aged man with a history of carditis on a systemic steroid who developed vomiting and rigor. Four physicians, including a pediatric intensivist, responded to the emergency call. In the second case, a pediatric trainee who was the only onboard medical personnel was summoned for help when a middle-aged man developed acute shortness of breath while traveling on a commercial flight. The cases illustrate the challenges and issues on the critical decisions of diagnosis, resuscitation, and whether the flight had to be returned or diverted. An extensive literature search is made to summarize the evidence available for these decisions and challenges. Epidemiology and outcomes associated with these medical emergencies are reviewed. In-flight medical emergencies are not rare. Physicians of all disciplines should be prepared to deal with these emergencies and make sensible decisions when equipment and resources are likely to be limited.

Invasive fungal infections in critically ill children: epidemiology, risk factors and antifungal drugs.

Background: Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to Candida species. Aspergillus, Zygomycetes and Fusarium are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children. Methods: A PubMed search was conducted with Clinical Queries using the key terms "antifungal", "children", "critical care" AND "paediatric intensive care unit" OR "PICU". The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics. Results: Candida and Aspergillus spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. Candida albicans is the principal Candida spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5-3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins. Conclusions: Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for Candida spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment.This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.

Invasive fungal infections in the Paediatric Intensive Care Unit: A Hong Kong Study.

INTRODUCTION: Invasive fungal infections (IFI) cause significant mortality and morbidity in the Paediatric Intensive Care Unit (PICU). Early recognition and prompt treatment of invasive fungal infections are important. This article reviewed the mortality and morbidity of IFIs in the PICU of Hong Kong Children's Hospital.

Methods: Retrospective review of all PICU admissions from April 2019 to May 2021. The following data were retrieved: age, gender, diagnosis, comorbidity, clinical manifestation, type of fungus, duration of stay at PICU, absolute neutrophil count, use of immunosuppressive therapy, presence of central venous catheter and use of total parental nutrition. The primary outcomes were the incidence and mortality of IFIs among PICU patients. The secondary outcomes were risk factors for developing IFI in PICU and clinical course of IFIs. Numerical variables were compared between groups by Mann-Whitney U test and categorical variables by Fisher's exact test.

Results: There were 692 PICU admissions over the study period from April 2019 to May 2021. There were 24 death cases during this period of time. The crude mortality was 3%. Fourteen patients (2%) fulfilling the criteria for IFIs were identified using hospital electronic record system and according to PICU documentation. Eight of these 14 patients (57%) had hematological malignancy, 2 (17%) had solid tumours and 4 had non-oncological conditions. There were 4 (29%) patients who had received hematopoietic stem cells transplant because of oncological problems. Six patients (43%) were neutropenic with absolute neutrophil count less than 1x 109 at diagnosis of IFI. Six (43%) had received immunosuppressive therapy including steroid, cyclosporin A, Mycophenolate mofetil (MMF), Sirolimus or tacrolimus. 12 (86%) had had central venous catheter. Eight (57%) were on parenteral nutrition. Rhizopus or Aspergillus infection (5/14) were associated with nonsurvival (p = 0.031).

Conclusion: All patients with IFIs managed in the PICU have haemato-oncology diseases or are recipients of stem cell transplantation. IFIs with Rhizopus or Aspergillus as a group are associated with high mortality in the PICU. Awareness of this pathology with prompt diagnosis and treatment may improve the outcome of these infections and reduce the mortality.

A case series of appendicitis and pseudo-appendicitis in a paediatric intensive care unit.

INTRODUCTION: Appendicitis is a common childhood condition that can be diagnostically challenging. Severe cases may necessitate support in the critical or intensive care unit. These "critical appendicitis diagnoses" have rarely been described. CASE DESCRIPTION: We retrospective reviewed the PICU database of the Hong Kong Children's Hospital and identified cases of suspected and confirmed appendicitis. Clinical features, radiologic findings and final diagnosis of each case were summarized and reported in this case series. We review six anonymized cases of appendicitis managed in a paediatric intensive care unit (PICU) to illustrate the different age spectrum and clinical manifestations of the condition. Rupture of the inflamed appendix, peritonitis and pancreatitis were some of the complications encountered. Crohn disease was found in one case as an underlying diagnosis. Also, one girl clinically diagnosed with appendicitis was found to be a case of ruptured hepatoblastoma with no appendicitis (i.e., pseudoappendicitis). CONCLUSION: Prompt diagnosis, surgical removal of the inflamed appendix, and use of appropriate antimicrobials when indicated are essential in reducing mortality and morbidity associated with severe appendicitis. Significant premorbid conditions such as acute myeloid leukemia, mitochondrial encephalopathy lactic acidosis syndrome (MELAS), inflammatory bowel disease and complications may be present in patients needing intensive care as is illustrated in the present cases. Pseudoappendicitis is an important differential diagnosis. Imaging is crucial and useful in establishing and confirming the diagnosis of appendicitis and pseudo-appendicitis in these PICU cases.

The successful application of hemoadsorption for extracorporeal liver support in a child with acute liver failure.

A 6-year-old boy developed acute liver failure with hepatic coma due to drug rash with eosinophilia and systemic symptoms (DRESS) after multiple antibiotics exposure. He had hyperbilirubinemia, elevated serum bile acids and hyperammonemia with peak serum levels of total bilirubin, direct bilirubin, bile acids and ammonia measuring 418, 328, 174, and 172 µmol/L respectively. In addition to the use of systemic steroid and other supportive therapy, he also received three sessions of hemoadsorption using the Cytosorb® column incorporated into the continuous renal replacement therapy circuit as extracorporeal liver support for a total duration of 75 h, which brought down his serum levels of total bilirubin to 119 µmol/L, bile acids to 58 µmol/L, and ammonia to 55 µmol/L. His conscious level gradually regained coupling an improvement of liver function. Except for mild thrombocytopenia and electrolyte disturbances, the therapy was well tolerated with no major complication encountered. Our case demonstrated that hemoadsorption can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure. The potential role and technical concerns of applying such technique in pediatric patients requires further evaluation in future studies.

Pediatric Extracorporeal Life Support Transport in Western Canada: Experience over 14 years.

This retrospective cohort study describes all children transported on extracorporeal life support (ECLS) by the Stollery Children's Hospital Pediatric Transport team (SCH-PTT) between 2004 and 2018. We compared outcomes and complications between primary (SCH-PTT performed ECLS cannulation) vs. secondary (cannulation performed by referring facility) transports, as well as secondary transports from referring centers with and without an established ECLS cannulation program. SCH-PTT performed 68 ECLS transports during the study period. Median (IQR) transport distance was 298 (298-1,068) kilometers. Mean (SD) times from referral call to ECLS-initiation were: primary transports 7.8 (2.9) vs. 2.5(3.5) hours for secondary transports, p value < 0.001. Complications were common (n = 65, 95%) but solved without leading to adverse outcomes. There were no significant differences in the number of complications between primary and secondary transports. There was no significant difference in survival to ECLS decannulation between primary 9 (90%) and secondary transports 43 (74%), p value = 0.275. ECLS survival was higher for children cannulated by the SCH-PTT or a center with an ECLS cannulation program: 42 (82%) vs. 10 (59%), p value = 0.048. Critically ill children on ECLS can be safely transported by a specialized pediatric ECLS transport team. Secondary transports from a center with an ECLS cannulation program are also safe and have similar results as primary transports.

Self-perceived disease control in childhood eczema.

BACKGROUND: Atopic eczema (AE) is a common relapsing inflammatory skin disease in children which is often associated with chronicity and poor quality of life. Unlike atopic asthma, control of AE is seldom assessed in therapeutics. AIM: To investigate the utility of a Traffic Light Control (TLC) system as a measurement/assessment of self-perceived eczema control. METHODS: This is a prospectively study of all Chinese children (aged 6-18 years old) with eczema attending the pediatric dermatology clinic of a tertiary hospital from January to June 2020. Eczema control, eczema severity, quality of life and biophysical skin condition of consecutive patients at the pediatric dermatology clinic of a teaching hospital were evaluated with the validated Chinese versions of Depressive, Anxiety, Stress Scales (DASS-21), Patient Oriented Eczema Measure (POEM), transepidermal water loss (TEWL), and stratum corneum skin hydration (SH), respectively. With a visual TLC analogy, patients were asked if their eczema is under control (green light), worsening (yellow) or in flare-up (red light). RESULTS: Among AE patients (n = 36), self-perceived TLC as green (under control), amber (worsening) and red (flare up) reflected acute and chronic severity (SCORAD, NESS, POEM) and quality of life (CDLQI) (p < .0001), but not SH, TEWL or Depression, anxiety and stress. CONCLUSIONS: Eczema control can be semi-quantified with a child-friendly TLC self-assessment system. AE patients reporting worse eczema control have worse acute and chronic eczema severity, more impairment of quality of life; but not the psychologic symptoms of depression, anxiety and stress or skin hydration or transepidermal water loss. TLC can be linked to an eczema action plan to guide patient management.

Drugs for paediatric hyperinflammatory syndromes.

Background: Many syndromes are associated with exaggerated inflammation. Children with hyperinflammatory syndromes often present with vague and non-specific symptoms that pose diagnostic and management challenges. The recent literature seems biased towards referring these syndromes only to the multisystem inflammatory syndrome in children (MIS-C) that is associated with COVID-19. The purpose of this paper is to provide an updated narrative review on the pathophysiology, manifestations and management approaches for common hyperinflammatory syndromes. Methods: An extensive PubMed search of all publications in the English literature was performed with Clinical Queries for various hyperinflammatory syndromes and conditions using the undermentioned Medical Subject Headings: "hyperinflammation", "hyperinflammatory syndromes", "sepsis syndrome", "severe inflammatory response syndrome" and "acute respiratory distress syndrome". Categories were limited to reviews and clinical trials for the age range from birth to 18 years. Results: The criteria, presentation and management of these hyperinflammatory syndromes are described. Hyperinflammatory syndromes refer to a basket of inflammatory syndromes often associated with multisystem involvement and aberrant cytokine release and should be differentiated from autoinflammatory, autoimmune and hyperimmune syndromes. The major subtypes of hyperinflammatory syndromes, including macrophage activation syndrome, haemophagocytic lymphohistiocytosis, cytokine release syndrome and cytokine storm syndrome, are described. MIS-C associated with SARS-CoV-2 represents the latest addition. It must be understood that the syndrome is not exclusive to COVID-19 but could be caused by various viral infections. Early recognition, prompt and proactive treatment can reduce potential complications and improve outcomes and survival rates in paediatric patients. Anti-inflammatory medications for the management of these syndromes are described. Conclusion: The incidence of these hyperinflammatory conditions is generally low in comparison to other disease conditions. Except for paediatric inflammatory multisystem syndrome/MIS-C, the mortality is high and the hospital stay is prolonged in affected patients. Acute and critical care physicians must be aware of these conditions and their initial management. Corticosteroids are often used in the initial phrase but various disease-specific drugs and biologics are needed in subsequent management and expert management of these often-difficult conditions is crucial.