Extracorporeal Membrane Oxygenation in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: To systematically review and assimilate literature on children receiving extracorporeal membrane oxygenation (ECMO) support in pediatric acute respiratory distress syndrome (PARDS) with the goal of developing an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research. DATA SOURCES: Electronic searches of MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: The search used a medical subject heading terms and text words to capture studies of ECMO in PARDS or acute respiratory failure. Studies using animal models and case reports were excluded from our review. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. There were 18 studies identified for full-text extraction. When pediatric data was lacking, adult and neonatal data from randomized clinical trials and observational studies were considered. Six clinical recommendations were generated related to ECMO indications, initiation, and management in PARDS. There were three good practice statements generated related to ECMO indications, initiation, and follow-up in PARDS. Two policy statements were generated involving the impact of ECMO team organization and training in PARDS. Last, there was one research statement. CONCLUSIONS: Based on a systematic literature review, we propose clinical management, good practice and policy statements within the domains of ECMO indications, initiation, team organization, team training, management, and follow-up as they relate to PARDS.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Hormone Replacement Therapy.

OBJECTIVE: To provide an overview of the current literature on the use of hormone replacement therapies in pediatric cardiac critical care. DATA SOURCES: PubMed, EMBASE, and the Cochrane Library were searched using keywords relevant to the hormonal therapy, with no limits on language but restricting the search to children 0-18 years old. STUDY SELECTION: All clinical studies believed to have relevance were considered. Where studies in children were sparse, additional evidence was sought from adult studies. DATA EXTRACTION: All relevant studies were reviewed, and the most relevant data were incorporated in this review. DATA SYNTHESIS: All authors of this review contributed to the appraisal of the data extracted. Challenges and revisions by the authors were conducted by group e-mail debate. CONCLUSIONS: Glycemic control: although it is likely that some children could benefit, the routine use of tight glycemic control cannot be recommended in children after cardiac surgery. Thyroid hormone replacement: routine use of thyroid hormone replacement to normalize levels after cardiac surgery cannot be recommended on current evidence. Until further evidence from adequately powered studies is available, therapeutic decisions should be based on individual patient circumstances. Corticosteroids: 1) cardiopulmonary bypass: although studies seem to favor steroid administration during surgery with cardiopulmonary bypass, a large randomized controlled trial is required before strong recommendations can be made; 2) refractory hypotension: the evidence for the use of steroid replacement in refractory hypotension is poor, and no firm recommendations can be made; and 3) abnormal adrenal function after cardiac surgery: there is inadequate evidence on which to make recommendations on the use of corticosteroid replacement in children with critical illness-related corticosteroid insufficiency in children following cardiac surgery.

Endocrinologic Diseases in Pediatric Cardiac Intensive Care.

OBJECTIVES: The objectives of this review are to discuss the pathophysiology, clinical impact and treatment of hyperglycemia, and disturbances in thyroid and adrenal function prior to and following cardiac surgery in children. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Disturbances in glucose metabolism and thyroid and adrenal function are common in critically ill children with cardiac disease and in particular in children undergoing cardiac surgery for complex congenital heart disease. An understanding of the pathophysiology, clinical impact and treatment of these disturbances is essential for the management of these at risk patients.

Extracorporeal support in children with pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVE: Extracorporeal life support has undergone a revolution in the past several years with the advent of new, miniaturized equipment and success in supporting patients with a variety of illnesses. Most experience has come with the use of extracorporeal membrane oxygenation, a modified form of cardiopulmonary bypass that can support the heart, lungs, and circulation for days to months at a time. To describe the recommendations for the use of extracorporeal membrane oxygenation in children with pediatric acute respiratory distress syndrome based on a review of the literature and expert opinion. DESIGN: Consensus conference of experts in pediatric acute lung injury. METHODS: A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. The extracorporeal support subgroup comprised two international experts. When published data were lacking, a modified Delphi approach emphasizing strong professional agreement was used. RESULTS: The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the topics related to pediatric acute respiratory distress syndrome, 11 of which related to extracorporeal support. All recommendations had agreement, with 10 recommendations (91%) achieving strong agreement. These recommendations included the utilization of extracorporeal support for reversible causes of pediatric acute respiratory distress syndrome, consideration of quality of life when making the decision to use extracorporeal support, and the use of the Extracorporeal Life Support Organization registry to report all extracorporeal support activity, among others. CONCLUSIONS: Pediatric extracorporeal membrane oxygenation for pediatric acute respiratory distress syndrome could benefit from more specific data collection and collaboration of focused investigators to establish validated criteria for optimal application of extracorporeal membrane oxygenation and patient management protocols. Until that time, consensus opinion offers some insight into guidelines.

Bivalirudin or heparin for systemic anticoagulation during pediatric extracorporeal membrane oxygenation: Multicenter retrospective study.

BACKGROUND: The objective of this study is to evaluate the outcomes of unfractionated heparin (UFH) compared to bivalirudin anticoagulation in pediatric ExtraCorporeal Membrane Oxygenation (ECMO). METHODS: A multicenter retrospective study, that included pediatric patients <18 years of age, who were supported on ECMO between June 2017 and May 2020. Patients treated with UFH were matched 2:1 by age and type of ECMO support to the bivalirudin group. RESULTS: The bivalirudin group (75 patients) were matched to 150 patients treated with UFH. Baseline characteristics and comorbidities of the two groups were similar. Veno-Arterial ECMO was the most common mode (141/225 [63 %]) followed by extracorporeal cardiopulmonary resuscitation (48/225 [21 %]). Bivalirudin treatment was associated with lower odds of bleeding events (aOR 0.23, 95%CI 0.12-0.45, p < 0.001) and lower odds of thrombotic events (aOR 0.48, 95%CI 0.23-0.98, p = 0.045). Patients who received bivalirudin had lesser odds for transfusion with fresh frozen plasma, and platelets (aOR 0.26, CI 0.12-0.57, p ≤0.001 and aOR 0.28, CI 0.15-0.53, p < 0.001, respectively). After adjusting for the type of ECMO support and adjusting for age, bivalirudin was associated with a decrease in hospital mortality by 50 % compared to the UFH group (aOR 0.50, 95%CI 0.27-0.93, p = 0.028). Similarly, for neurological disability at time of discharge, bivalirudin was associated with higher odds of intact neurological outcomes compared to UFH (OR 1.99 [95%CI 1.13-3.51], p = 0.017). CONCLUSIONS: This study demonstrated that effective anticoagulation can be achieved with bivalirudin, which was associated with lesser odds of bleeding events and utilization of blood products. Bivalirudin, in comparison with UFH, was associated with greater odds of hospital survival and intact neurological function at the time of discharge. A prospective randomized trial is required to validate the results of this study.

Novel postoperative use of beta-blocking medication for infants with left ventricular outflow obstruction and diastolic myocardial dysfunction.

Severe left ventricular outflow obstruction often is associated with diastolic left ventricular myocardial dysfunction and tachycardia despite successful initial treatment. The authors have used esmolol to lower heart rate in this setting for successful weaning of patients from ventilation in postoperative recovery. Their limited experience supports the beneficial effect of continuous esmolol administration on infants with persistent tachycardia and severe left ventricular diastolic dysfunction in postoperative cardiac intensive care.

Monitoring in pediatric cardiac critical care: a worldwide perspective.

Our ability to directly monitor the mechanisms that govern cellular function, oxygen use, and survival is minimal. Therefore, in critically ill children, surrogate markers are used to try to detect evolving or established hypoxia. These surrogate markers are best used in combination and are complementary to clinical examination. Regardless of resource limitations, we propose that the availability of certain monitoring tools form a standard of care without which pediatric cardiac critical care cannot be safely or optimally provided. These tools include standard invasive hemodynamic monitoring with electrocardiography, lactate measurement, central venous oxygen saturation, and echocardiography. Ultimately, monitoring is only useful when the clinician observes a specific value or trend and has the expertise to act appropriately.

Inhaled nitric oxide therapy in adults: European expert recommendations.

BACKGROUND: Inhaled nitric oxide (iNO) has been used for treatment of acute respiratory failure and pulmonary hypertension since 1991 in adult patients in the perioperative setting and in critical care. METHODS: This contribution assesses evidence for the use of iNO in this population as presented to a expert group jointly organised by the European Society of Intensive Care Medicine and the European Association of Cardiothoracic Anaesthesiologists. CONCLUSIONS: Expert recommendations on the use of iNO in adults were agreed on following presentation of the evidence at the expert meeting held in June 2004.

Inhaled nitric oxide therapy in neonates and children: reaching a European consensus.

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting.

The Council for International Organizations and Medical Sciences (CIOMS) guidelines on ethics of clinical trials.

Numerous bodies from many countries, including governments, government regulatory departments, research organizations, medical professional bodies, and health care providers, have issued guidance or legislation on the ethical conduct of clinical trials. It is possible to trace the development of current guidelines back to the post-World War II Nuremburg war crimes trials, more specifically the "Doctors' Trial." From that trial emerged the Nuremburg Code, which set out basic principles to be observed when conducting research involving human subjects and which subsequently formed the basis for comprehensive international guidelines on medical research, such as the Declaration of Helsinki. Most recently, the Council for International Organizations and Medical Sciences (CIOMS) produced detailed guidelines (originally published in 1993 and updated in 2002) on the implementation of the principles outlined in the Declaration of Helsinki. The CIOMS guidelines set in an appropriate context the challenges of present-day clinical research, by addressing complex issues including HIV/AIDS research, availability of study treatments after a study ends, women as research subjects, safeguarding confidentiality, compensation for adverse events, as well guidelines on consent.