Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU.

OBJECTIVES: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission. DESIGN: National prospective cohort study March 2020 to November 2021. SETTING: Seven PICUs in the Netherlands. PATIENTS: Children with MIS-C (0-17 yr) admitted to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found. CONCLUSIONS: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated.

Extracorporeal life support provision in COVID-19 patients - An international EuroELSO 2022 update survey.

INTRODUCTION: An analysis on the ECLS use for patients with respiratory or cardiac support in COVID-19 based on an international response to EuroELSO survey, aims to generate a more comprehensive understanding of ECLS role during the recent viral pandemic. METHODS: EuroELSO announced the survey at the 10th annual congress in London, May 2022. The survey covered 26 multiple-choice questions. RESULTS: The survey returned 69 questionnaires from 62 centers across 22 European countries and seven centers across five non-European countries. Most of the centers providing ECLS for COVID-19 patients had more than 30 runs for respiratory support since December 2019. In the same period, at least 31 runs in adult COVID-19 patients have been performed in 48 of 69 centers (69.6%). The reported pediatric data from 18 centers is limited to less than the patients per center. CONCLUSION: Majority of the COVID-19 patients received respiratory ECLS support and adult patients dominated. The indications and contraindications are broadly aligned with available guidelines. Most of the centers considered age >65 or biological age as a relative or absolute contraindication for ECLS in COVID-19. ECLS withdrawal criteria in COVID-19 are controversial because the long-term outcomes after ECLS in COVID-19 and the impact of critical illness and the impact of long-COVID are still not known.

Treatment of Post-Coarctectomy Hypertension With Labetalol-A 9-Year Single-Center Experience.

BACKGROUND: Although considering the pathophysiology of post-coarctectomy hypertension, ß-blockers should be effective, experience with labetalol for treatment is limited in the literature. METHODS: Retrospective collection and analysis of data in children aged ≤6 years following coarctectomy in our tertiary care university medical center between January 2009 and June 2018. RESULTS: 96 patients were included, 45 were treated with intravenous labetalol and 51 received no treatment. Median time to maximum dose received (median 1.1 mg/kg/h) was 2.7 h, and median time to the reduction of labetalol dose was 8.3 h. No antihypertensives had to be added. In one child, labetalol was switched to nitroprusside due to bronchoconstriction. Of patients receiving intravenous labetalol, 48% had been switched to oral labetalol at discharge. CONCLUSIONS: Intravenous labetalol is a fast, effective, and safe drug to treat hypertension following aortic coarctation repair. Labetalol is easily converted to oral therapy when the continuation of treatment is considered necessary.

The horizon of pediatric cardiac critical care.

Pediatric Cardiac Critical Care (PCCC) is a challenging discipline where decisions require a high degree of preparation and clinical expertise. In the modern era, outcomes of neonates and children with congenital heart defects have dramatically improved, largely by transformative technologies and an expanding collection of pharmacotherapies. Exponential advances in science and technology are occurring at a breathtaking rate, and applying these advances to the PCCC patient is essential to further advancing the science and practice of the field. In this article, we identified and elaborate on seven key elements within the PCCC that will pave the way for the future.

Anti-Xa versus time-guided anticoagulation strategies in extracorporeal membrane oxygenation: a systematic review and meta-analysis.

The purpose was to compare time-based vs anti-Xa-based anticoagulation strategies in patients on ECMO. We conducted a systematic review and meta-analysis using multiple electronic databases and included studies from inception to July 19, 2019. The proportion of bleeding, thrombosis, and mortality were evaluated.Twenty-six studies (2,086 patients) were included. Bleeding occurred in 34.2% (95%CI 25.1;43.9) of the patients with anti-Xa-based versus 41.6% (95%CI 24.9;59.4) of the patients with time-based anticoagulation strategies. Thrombosis occurred in 32.6% (95%CI 19.1;47.7) of the patients with anti-Xa-based versus 38.4% (95%CI 22.2;56.1) of the patients with time-based anticoagulation strategies. And mortality rate was 35.4% (95%CI 28.9;42.1) of the patients with anti-Xa-based versus 42.9% (95%CI 36.9;48.9) of the patients with time-based anticoagulation strategies. Among the seven studies providing results from both anticoagulation strategies, significantly fewer bleeding events occurred in the anti-Xa-based anticoagulation strategy (adjusted OR 0.49 (95%CI 0.32;0.74), p < 0.001) and a significantly lower mortality rate (adjusted OR 0.61 (95%CI 0.40;0.95), p = 0.03). There was no significant difference in thrombotic events (adjusted OR 0.91 (95%CI 0.56;1.49), p = 0.71). In these seven observational studies, only a small fraction of the patients were adults, and data were insufficient to analyze the effect of the type of ECMO.In this meta-analysis of observational studies of patients on ECMO, an anti-Xa-based anticoagulation strategy, when compared to a time-based strategy, was associated with fewer bleeding events and mortality rate, without an increase in thrombotic events.

Rhinovirus Detection in the Nasopharynx of Children Undergoing Cardiac Surgery Is Not Associated With Longer PICU Length of Stay: Results of the Impact of Rhinovirus Infection After Cardiac Surgery in Kids (RISK) Study.

OBJECTIVES: To determine whether children with asymptomatic carriage of rhinovirus in the nasopharynx before elective cardiac surgery have an increased risk of prolonged PICU length of stay. STUDY DESIGN: Prospective, single-center, blinded observational cohort study. SETTING: PICU in a tertiary hospital in The Netherlands. PATIENTS: Children under 12 years old undergoing elective cardiac surgery were enrolled in the study after informed consent of the parents/guardians. INTERVENTIONS: The parents/guardians filled out a questionnaire regarding respiratory symptoms. On the day of the operation, a nasopharyngeal swab was obtained. Clinical data were collected during PICU admission, and PICU/hospital length of stay were reported. If a patient was still intubated 3 days after operation, an additional nasopharyngeal swab was collected. Nasopharyngeal swabs were tested for rhinovirus and other respiratory viruses with polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Of the 163 included children, 74 (45%) tested rhinovirus positive. Rhinovirus-positive patients did not have a prolonged PICU length of stay (median 2 d each; p = 0.257). Rhinovirus-positive patients had a significantly shorter median hospital length of stay compared with rhinovirus-negative patients (8 vs 9 d, respectively; p = 0.006). Overall, 97 of the patients (60%) tested positive for one or more respiratory virus. Virus-positive patients had significantly shorter PICU and hospital length of stay, ventilatory support, and nonmechanical ventilation. Virus-negative patients had respiratory symptoms suspected for a respiratory infection more often. In 31% of the children, the parents reported mild upper respiratory complaints a day prior to the cardiac surgery, this was associated with postextubation stridor, but no other clinical outcome measures. CONCLUSIONS: Preoperative rhinovirus polymerase chain reaction positivity is not associated with prolonged PICU length of stay. Our findings do not support the use of routine polymerase chain reaction testing for respiratory viruses in asymptomatic children admitted for elective cardiac surgery.

Position Paper on Global Extracorporeal Membrane Oxygenation Education and Educational Agenda for the Future: A Statement From the Extracorporeal Life Support Organization ECMOed Taskforce.

OBJECTIVES: The purpose of this position paper is two-fold: first, to describe the state of extracorporeal membrane oxygenation education worldwide, noting current limitations and challenges; and second, to put forth an educational agenda regarding opportunities for an international collaborative approach toward standardization. DESIGN: Relevant medical literature was reviewed through literature search, and materials from national organizations were accessed through the Internet. Taskforce members generated a consensus statement using an iterative consensus process through teleconferences and electronic communication. SETTING: In 2018, the Extracorporeal Life Support Organization convened the ECMOed Taskforce at two structured, face-to-face meetings of 40 healthcare practitioners and educators with expertise in caring for the extracorporeal membrane oxygenation patient and in extracorporeal membrane oxygenation education. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ECMOed Taskforce identified seven educational domains that would benefit from international collaborative efforts. Of primary importance, the Taskforce outlined actionable items regarding 1) the creation of a standardized extracorporeal membrane oxygenation curriculum; 2) defining criteria for an extracorporeal membrane oxygenation course as a vehicle for delivering the curriculum; 3) outlining a mechanism for evaluating the quality of educational offerings; 4) utilizing validated assessment tools in the development of extracorporeal membrane oxygenation practitioner certification; and 5) promoting high-quality educational research to guide ongoing educational and competency assessment development. CONCLUSIONS: Significant variability and limitations in global extracorporeal membrane oxygenation education exist. In this position paper, we outline a road map for standardizing international extracorporeal membrane oxygenation education and practitioner certification. Ongoing high-quality educational research is needed to evaluate the impact of these initiatives.

Neonatal Cardiac ECMO in 2019 and Beyond.

Worldwide, the use of Extracorporeal Membrane Oxygenation (ECMO) for cardiac failure has been steadily increasing in the neonatal population and has become a widely accepted modality. Especially in centers caring for children with (congenital) heart disease, ECMO is now an essential part of care available for those with severe heart failure as a bridge to recovery, long term mechanical support, or transplantation. Short-term outcomes depend very much on indication. Hospital survival is ~40% for all neonatal cardiac ECMO patients combined. ECMO is being used for pre- and/or post-operative stabilization in neonates with congenital heart disease and in neonates with medical heart disease such as myocarditis, cardiomyopathy or refractory arrhythmias. ECMO use during resuscitation (ECPR) or for sepsis is summarized elsewhere in this special edition of Frontiers in Pediatrics. In this review article, we will discuss the indications for neonatal cardiac ECMO, the difficult process of patients' selection and identifying the right timing to initiate ECMO, as well as outline pros and cons for peripheral vs. central cannulation. We will present predictors of mortality and, very importantly, predictors of survival: what can be done to improve the outcomes for your patients. Furthermore, an overview of current insights regarding supportive care in neonatal cardiac ECMO is given. Additionally, we will address issues specific to neonates with single ventricle physiology on ECMO, for example cannulation strategies and the influence of shunt type (Blalock-Taussig shunt vs. "right ventricle to pulmonary artery" shunt). We will not only focus on short term outcomes, such as hospital survival, but also on the importance of long-term neuro-developmental outcomes, and we will end this review with suggestions for future research.

Hypoplastic left heart syndrome: from fetus to fontan.

The care of children with hypoplastic left heart syndrome is constantly evolving. Prenatal diagnosis of hypoplastic left heart syndrome will aid in counselling of parents, and selected fetuses may be candidates for in utero intervention. Following birth, palliation can be undertaken through staged operations: Norwood (or hybrid) in the 1st week of life, superior cavopulmonary connection at 4-6 months of life, and finally total cavopulmonary connection (Fontan) at 2-4 years of age. Children with hypoplastic left heart syndrome are at risk of circulatory failure their entire life, and selected patients may undergo heart transplantation. In this review article, we summarise recent advances in the critical care management of patients with hypoplastic left heart syndrome as were discussed in a focused session at the 12th International Conference of the Paediatric Cardiac Intensive Care Society held on 9 December, 2016, in Miami Beach, Florida.

The Perspective of the Intensivist on Inotropes and Postoperative Care Following Pediatric Heart Surgery: An International Survey and Systematic Review of the Literature.

INTRODUCTION: Inotropes are frequently being used in children undergoing heart surgery to prevent or treat low cardiac output syndrome (LCOS). There is only limited evidence that inotropes actually positively influence postoperative outcome. Our aim was to describe the current international practice variation in the use of inotropes following congenital heart surgery. METHODS: We developed an online survey regarding the postoperative use of inotropes. We sent an invitation to all 197 registered members of the Pediatric Cardiac Intensive Care Society (PCICS) to participate in the survey. We also performed a systematic review of the literature. RESULTS: Ninety-eight people (50%) responded, representing 62 international centers. Milrinone is routinely used perioperatively by 90 respondents (97%). Adrenaline/epinephrine is routinely used by 43%, dopamine by 36%, dobutamine by 11%, and levosimendan by 6%. Steroids are used routinely by 54% before initiating cardiopulmonary bypass. Vasopressin is used by 44% of respondents. The development of LCOS is monitored with lactate in 99% of respondents, physical examination (98%), intermittent mixed venous saturation (76%), continuous mixed venous saturation (13%), echocardiography (53%), core-peripheral temperature gap (29%), near-infrared spectrometry (25%), and 4% use cardiac output monitors (PiCCO, USCOM). To improve cardiac output, 42% add/increase milrinone, 37% add adrenaline, and 15% add dopamine. Rescue therapy is titrated individually, based on the patients' pathophysiology. A systematic review of the literature failed to show compelling evidence with regard to the benefit of inotropes. CONCLUSIONS: Despite the lack of sufficient evidence, milrinone is used by the vast majority of caregivers following congenital heart surgery.

The Burdens of Offering: Ethical and Practical Considerations.

We reflect upon highlights of a facilitated panel discussion from the 2016 Pediatric Cardiac Intensive Care Society Meeting. The session was designed to explore challenges, share practical clinical experiences, and review ethical underpinnings surrounding decisions to offer intensive, invasive therapies to patients who have a poor prognosis for survival or are likely to be burdened with multiple residual comorbidities if survival is achieved. The discussion panel was representative of a variety of disciplines including pediatric cardiology, cardiac intensive care, nursing, and cardiovascular surgery as well as different health-care delivery systems. Key issues discussed included patient's best interests, physician obligations, moral distress, and communication in the context of decisions about providing therapy for patients with a poor prognosis.

Treatment Strategies for Paradoxical Hypertension Following Surgical Correction of Coarctation of the Aorta in Children.

BACKGROUND: Paradoxical hypertension after repair of coarctation of the aorta is a well-known phenomenon. The pathogenesis involves the activation of the sympathetic nervous system (first phase) and renin-angiotensin system (second phase). Only a limited number of different treatment strategies have been published in the literature, without any comparative studies. METHODS: Our aim was to describe the current international practice variation surrounding pharmacological treatment currently being employed to treat paradoxical hypertension following the repair of coarctation of the aorta in children. We performed an online survey among 197 members of the Pediatric Cardiac Intensive Care Society. We also conducted a systematic review of the literature regarding the treatment of paradoxical hypertension. RESULTS: Eighty-eight people (45%), from 62 different centers, responded and answered the questions regarding blood pressure control. Nitroprusside is the first drug of choice for initial blood pressure control in 66% of respondents, esmolol in 11%, labetalol in 11%, and angiotensin-converting enzyme inhibitors (ACEIs) are used by 3% of respondents. For oral blood pressure control after discharge from the pediatric intensive care unit, 75% of respondents use ACEIs, 18% use labetalol, and 12% use other beta-blockers (propranolol, carvedilol, atenolol, metoprolol). The systematic review identified 14 articles reporting pharmacological treatment of direct postoperative hypertension following coarctation repair. CONCLUSION: There is wide practice variability, due to the lack of sufficient compelling evidence. The majority (66%) of caregivers use nitroprusside to control blood pressure in the acute postoperative phase. The ACEIs are the drug of choice for chronic blood pressure control.

Higher Tinzaparin Dosing Is Needed to Achieve Target Anti-Xa Levels in Pediatric Cardiac Intensive Care Patients.

OBJECTIVES: This study was conducted to evaluate tinzaparin dosing and therapeutic drug monitoring. DESIGN: Retrospective study. SETTING: Single tertiary-level PICU. PATIENTS: Tinzaparin doses and anti-Xa levels from all children admitted to a PICU (from October 1, 2010, to December 31, 2013) were retrospectively analyzed. Thirty-nine children, median age of 13 months (interquartile range, 73 mo), with 46 episodes of newly started therapeutic tinzaparin were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Local hospital policy is to determine the first anti-Xa level after 3-4 doses, 4 hours post dose, targeting 0.5-1.0 IU/mL for therapeutic dosing. First anti-Xa levels were determined after 3.8 (± 2.4; range, 1-14) doses and were below the target range in 37 of 46 episodes (76%) of tinzaparin use: mean, 0.30 (± 0.11) IU/mL. Tinzaparin was then increased by 23% (± 19) in 23 of 37 episodes (62%), and further anti-Xa levels were determined. In 14 episodes, further levels were not available because of cessation of tinzaparin therapy. Target anti-Xa levels, 0.69 (± 0.24) IU/mL, were eventually reached in the PICU in 22 patients after a mean of 8.8 (± 7.3) doses. In the entire cohort, the dose required to achieve target anti-Xa levels was significantly higher (+51 [± 62] U/kg; p = 0.003) than the recommended starting dose. CONCLUSIONS: Target anti-Xa levels were reached with tinzaparin dosing in PICU patients after more than 8 doses, warranting further dose-effect research. Especially in the younger age group, substantially higher dose requirements than proposed in the internationally used guidelines are required. With the results of our study, we suggest a different therapeutic drug monitoring approach than that currently used.

Extracorporeal Membrane Oxygenation in Single Ventricle Lesions Palliated Via the Hybrid Approach.

BACKGROUND: Describing outcomes for children with hypoplastic left heart syndrome (HLHS) undergoing hybrid palliation (pulmonary artery band and stent placement in the patent ductus arteriosus) requiring extracorporeal membrane oxygenation (ECMO) support for cardiorespiratory failure. METHODS: We reviewed the Extracorporeal Life Support Organization database for all patients with a diagnosis of an HLHS undergoing hybrid stage 1 palliation supported with ECMO and those patients with hybrid palliation supported with ECMO after comprehensive stage 2 palliation. Patients were identified using a combination of International Classification of Diseases, Ninth Revision and registry diagnosis and procedure codes. We report survival to hospital discharge and ECMO complications. RESULTS: We identified 44 patients with HLHS requiring ECMO following stage 1 hybrid approach. Median age at cannulation was 13.5 days. Only 16% survived to hospital discharge. In all, 20 (50%) patients had a cardiac arrest prior to going onto ECMO and for 3 (19%) patients, ECMO was initiated during cardiopulmonary resuscitation. CONCLUSIONS: Overall survival for ECMO support in patients with HLHS palliated via the hybrid approach is very poor (16%) and is worse than 31% survival reported for ECMO after conventional stage 1 palliation. The reasons for these poor outcomes require further investigation.

A neonate with coexisting congenital cystic adenomatoid malformation of the lung and alveolar capillary dysplasia: a case report with review of literature.

OBJECTIVE: First report of a term neonate with coexistent congenital cystic adenomatoid malformation (CCAM) of the lung and alveolar capillary dysplasia (ACD). METHODS AND DESIGN: Case report and literature review. Our institutional review board waived the need for consent. SETTING: We describe a term neonate with antenatally diagnosed CCAM and persistent pulmonary hypertension of the newborn (PPHN) who underwent right upper lobe resection on day 9 of life. Histology confirmed CCAM but closer examination also showed ACD. Postoperatively pulmonary hypertension persisted despite high-frequency oscillation and inhaled nitric oxide, and she was placed on extracorporeal membrane oxygenation. Due to the lack of any improvement, intensive care treatment was withdrawn 4 days later. CONCLUSIONS: This is the first description of an association between these two rare malformations. Although a causative link between CCAM and ACD is possible, it is unlikely. ACD should always be considered as a cause of severe PPHN when persistent beyond 10 days, even if another etiology of PPHN is present.