Features of Intestinal Disease Associated With COVID-Related Multisystem Inflammatory Syndrome in Children.

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified syndrome that appears to be temporally associated with novel coronavirus 2019 infection. MIS-C presents with fever and evidence of systemic inflammation, which can manifest as cardiovascular, pulmonary, neurologic, and gastrointestinal (GI) system dysfunction. Presenting GI symptoms are seen in the majority, including abdominal pain, diarrhea, and vomiting. Any segment of the GI tract may be affected; however, inflammation in the ileum and colon predominates. Progressive bowel wall thickening can lead to luminal narrowing and obstruction. Most will have resolution of intestinal inflammation with medical therapies; however, in rare instances, surgical resection may be required.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Looking for trouble: Adherence to late-effects surveillance among childhood cancer survivors.

BACKGROUND: Childhood cancer survivors (CCSs) are at high risk of morbidity and mortality from long-term complications of their cancer treatment. The Children's Oncology Group developed screening guidelines to enable the early identification of and intervention for late effects of cancer treatment. There is a paucity of data on the adherence of CCSs to screening recommendations. PROCEDURE: A retrospective analysis of medical records to evaluate the rate of adherence of CCSs to the personalized, risk-based recommendations provided to them in the context of a structured long-term follow-up program over a 3-year period. RESULTS: Two hundred eighty-six CCSs visited the survivorship clinic 542 times during the 3-year study period. The overall rate of adherence to recommended screening was 74.2%. Using a univariate model and greater age at diagnosis and at screening recommendation were associated with decreased screening adherence. Gender, cancer diagnosis, radiation therapy, anthracycline exposure, and hematopoietic stem cell transplant were not significantly associated with adherence. In a multivariate model, age over 18 years at the time of the visit was significantly associated with decreased adherence (P < 0.0329) (odds ratio: 1.53, 95% confidence interval: 1.04-2.25). CONCLUSIONS: Adherence to recommended screening tests is suboptimal among CCSs, with lower rates of adherence in CCSs older than 18 years of age compared with those younger than 18 years of age. Given the morbidity and mortality from the late effects of therapy among young adult CCSs, it is critically important to identify and remove barriers to late-effects screening among CCSs.

Early oxygenation and ventilation measurements after pediatric cardiac arrest: lack of association with outcome.

OBJECTIVES: To explore oxygenation and ventilation status early after cardiac arrest in infants and children. We hypothesize that hyperoxia is common and associated with worse outcome after pediatric cardiac arrest. DESIGN: Retrospective cohort study. SETTING: Fifteen hospitals within the Pediatric Emergency Care Applied Research Network. PATIENTS: Children who suffered a cardiac arrest event and survived for at least 6 hours after return of circulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis of 195 events revealed that abnormalities in oxygenation and ventilation are common during the initial 6 hours after pediatric cardiac arrest. Hyperoxia was frequent, affecting 54% of patients. Normoxia was documented in 34% and hypoxia in 22% of patients. These percentages account for a 10% overlap of patients who had both hyperoxia and hypoxia. Ventilation status was more evenly distributed with hyperventilation observed in 38%, normoventilation in 29%, and hypoventilation in 46%, with a 13% overlap of patients who had both hyperventilation and hypoventilation. Derangements in both oxygenation and ventilation were common early after cardiac arrest such that both normoxia and normocarbia were documented in only 25 patients (13%). Neither oxygenation nor ventilation status was associated with outcome. After controlling for potential confounders, arrest location and rhythm were significantly associated with worse outcome; however, hyperoxia was not (odds ratio for good outcome, 1.02 [0.46, 2.84]; p = 0.96). CONCLUSIONS: Despite recent resuscitation guidelines that advocate maintenance of normoxia and normoventilation after pediatric cardiac arrest, this is uncommonly achieved in practice. Although we did not demonstrate an association between hyperoxia and worse outcome, the small proportion of patients kept within normal ranges limited our power. Preclinical data suggesting potential harm with hyperoxia remain compelling, and further investigation, including prospective, large studies involving robust recording of physiological derangements, is necessary to further advance our understanding of this important topic.

Early lactate elevations following resuscitation from pediatric cardiac arrest are associated with increased mortality*.

OBJECTIVE: To describe the association of lactate levels within the first 12 hours after successful resuscitation from pediatric cardiopulmonary arrest with hospital mortality. DESIGN: Retrospective cohort study. SETTING: Fifteen children's hospital associated with the Pediatric Emergency Care Applied Research Network. PATIENTS: Patients between 1 day and 18 years old who had a cardiopulmonary arrest, received chest compressions more than 1 minute, had a return of spontaneous circulation more than 20 minutes, and had lactate measurements within 6 hours of arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred sixty-four patients had a lactate sampled between 0 and 6 hours (lactate(0-6)) and were evaluable. Of those, 153 patients had a lactate sampled between 7 and 12 hours (lactate(7-12)). One hundred thirty-eight patients (52%) died. After controlling for arrest location, total number of epinephrine doses, initial rhythm, and other potential confounders, the odds of death per 1 mmol/L increase in lactate(0-6) was 1.14 (1.08, 1.19) (p < 0.001) and the odds of death per 1 mmol/L increase in lactate(7-12) was 1.20 (1.11, 1.30) (p < 0.0001). Area under the curve for in-hospital arrest mortality for lactate(0-6) was 0.72 and for lactate(7-12) was 0.76. Area under the curve for out-of-hospital arrest mortality for lactate(0-6) was 0.8 and for lactate(7-12) was 0.75. CONCLUSIONS: Elevated lactate levels in the first 12 hours after successful resuscitation from pediatric cardiac arrest are associated with increased mortality. Lactate levels alone are not able to predict outcomes accurately enough for definitive prognostication but may approximate mortality observed in this large cohort of children's hospitals.

Multicenter cohort study of out-of-hospital pediatric cardiac arrest.

OBJECTIVES: To describe a large cohort of children with out-of-hospital cardiac arrest with return of circulation and to identify factors in the early postarrest period associated with survival. These objectives were for planning an interventional trial of therapeutic hypothermia after pediatric cardiac arrest. METHODS: A retrospective cohort study was conducted at 15 Pediatric Emergency Care Applied Research Network clinical sites over an 18-month study period. All children from 1 day (24 hrs) to 18 yrs of age with out-of-hospital cardiac arrest and a history of at least 1 min of chest compressions with return of circulation for at least 20 mins were eligible. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-eight cases met study entry criteria; the overall mortality was 62% (85 of 138 cases). The event characteristics associated with increased survival were as follows: weekend arrests, cardiopulmonary resuscitation not ongoing at hospital arrival, arrest rhythm not asystole, no atropine or NaHCO3, fewer epinephrine doses, shorter duration of cardiopulmonary resuscitation, and drowning or asphyxial arrest event. For the 0- to 12-hr postarrest return-of-circulation period, absence of any vasopressor or inotropic agent (dopamine, epinephrine) use, higher lowest temperature recorded, greater lowest pH, lower lactate, lower maximum glucose, and normal pupillary responses were all associated with survival. A multivariate logistic model of variables available at the time of arrest, which controlled for gender, age, race, and asystole or ventricular fibrillation/ventricular tachycardia anytime during the arrest, found the administration of atropine and epinephrine to be associated with mortality. A second model using additional information available up to 12 hrs after return of circulation found 1) preexisting lung or airway disease; 2) an etiology of arrest drowning or asphyxia; 3) higher pH, and 4) bilateral reactive pupils to be associated with lower mortality. Receiving more than three doses of epinephrine was associated with poor outcome in 96% (44 of 46) of cases. CONCLUSIONS: Multiple factors were identified as associated with survival after out-of-hospital pediatric cardiac arrest with the return of circulation. Additional information available within a few hours after the return of circulation may diminish outcome associations of factors available at earlier times in regression models. These factors should be considered in the design of future interventional trials aimed to improve outcome after pediatric cardiac arrest.

Cost of survivorship care and adherence to screening-aligning the priorities of health care systems and survivors.

Childhood cancer survivors (CCS) experience significant morbidity due to treatment- related late effects and benefit from late-effects surveillance. Adherence to screening recommendations is suboptimal. Survivorship care programs often struggle with resource limitations and may benefit from understanding institution-level financial outcomes associated with patient adherence to justify programmatic development and growth. The purpose of this study is to examine how CCS adherence to screening recommendations relates to the cost of care, insurance status, and institution-level financial outcomes. A retrospective chart review of 286 patients, followed in a structured survivorship program, assessed adherence to the Children's Oncology Group follow-up guidelines by comparing recommended versus performed screening procedures for each patient. Procedure cost estimates were based on insurance status. Institutional profit margins and profit opportunity loss were calculated. Bivariate statistics tested adherent versus nonadherent subgroup differences on cost variables. A generalized linear model predicted the likelihood of adherence based on cost of recommended procedures, controlling for age, gender, race, and insurance. Adherence to recommended surveillance procedures was 50.2%. Nonadherence was associated with higher costs of recommended screening procedures compared to the adherent group estimates ($2,469.84 vs. $1,211.44). Failure to perform the recommended tests resulted in no difference in reimbursement to the health system between groups ($1,249.63 vs. $1,211.08). For the nonadherent group, this represented $1,055.13 in "lost profit opportunity" per visit for patients, which totaled $311,850 in lost profit opportunity due to nonadherence in this subgroup. In the final model, nonadherence was related to higher cost of recommended procedures (p < .0001), older age at visit (p = .04), Black race (p = .02), and government-sponsored insurance (p = .03). Understanding institutional financial outcomes related to patient adherence may help inform survivorship care programs and resource allocation. Potential financial burden to patients associated with complex care recommendations is also warranted.

Massive pulmonary embolism in children.

We present 3 children with massive pulmonary embolism and review 17 recent pediatric reports. Malignancies were a frequent cause (40%), and sudden death was common (60%). Compared with adults, diagnosis was more likely to be made at autopsy (P < .0001), more children were treated with embolectomy/thrombectomy (P = .0006), and mortality was greater (P = .03).

In-hospital versus out-of-hospital pediatric cardiac arrest: a multicenter cohort study.

OBJECTIVES: : To describe a large multicenter cohort of pediatric cardiac arrest (CA) with return of circulation (ROC) from either the in-hospital (IH) or the out-of-hospital (OH) setting and to determine whether significant differences related to pre-event, arrest event, early postarrest event characteristics, and outcomes exist that would be critical in planning a clinical trial of therapeutic hypothermia (TH). DESIGN: : Retrospective cohort study. SETTING: : Fifteen Pediatric Emergency Care Applied Research Network sites. PATIENTS: : Patients aged 24 hours to 18 years with either IH or OH CA who had a history of at least 1 minute of chest compressions and ROC for at least 20 minutes were eligible. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : A total of 491 patients met study entry criteria with 353 IH cases and 138 OH cases. Major differences between the IH and OH cohorts were observed for patient prearrest characteristics, arrest event initial rhythm described, and arrest medication use. Several postarrest interventions were used differently, however, the use of TH was similar (<5%) in both cohorts. During the 0-12-hour interval following ROC, OH cases had lower minimum temperature and pH, and higher maximum serum glucose recorded. Mortality was greater in the OH cohort (62% vs. 51%, p = 0.04) with the cause attributed to a neurologic indication much more frequent in the OH than in the IH cohort (69% vs. 20%; p < 0.01). CONCLUSIONS: : For pediatric CA with ROC, several major differences exist between IH and OH cohorts. The finding that the etiology of death was attributed to neurologic indications much more frequently in OH arrests has important implications for future research. Investigators planning to evaluate the efficacy of new interventions, such as TH, should be aware that the IH and OH populations differ greatly and require independent clinical trials.

Parental presence on pediatric intensive care unit rounds.

OBJECTIVE: To comprehensively evaluate the effect of parental presence on pediatric intensive care unit rounds. STUDY DESIGN: A prospective, observational and survey-based study comprised of (1) observation of rounds (2) "rounding event assessments" (brief surveys specific to 1 rounding event, completed by health care providers [HCPs] n = 375) (3) qualitative interviews with parents (36 who joined rounds and 16 who elected not to join), and (4) qualitative written surveys from HCPs (63 nurses, 39 doctors). RESULTS: Eighty-one percent of parents who chose to join rounds reported that participation increased their overall satisfaction with their child's care. In 57% of rounding events, at least 1 HCP learned new, pertinent information from the parents. However, in 32% of rounding events, at least 1 HCP believed parental presence limited discussion. Forty-seven percent of parents who participated in rounds and 88% of those who chose not to participate volunteered that participation has the potential to increase parental confusion and anxiety (P = .02). CONCLUSIONS: Most parents and physicians agree that parents should be invited to participate on rounds. Parents report increased satisfaction from participation, and parents provide new information when on rounds. However, parental presence may limit discussion during rounds which may adversely affect patient care.

Children undergoing heart transplant are at increased risk for postoperative vasodilatory shock.

OBJECTIVE: To determine the incidence of vasodilatory shock (VDS) in children after cardiopulmonary bypass (CPB), and to describe this syndrome of post-CPB VDS in children. DESIGN: Prospective, observational. SETTING: Pediatric and neonatal intensive care units in a tertiary care, children's hospital. PATIENTS: Three hundred children undergoing CPB. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Three hundred subjects undergoing CPB were evaluated for clinical evidence of VDS following CPB. The incidence of post-CPB VDS was 3%. Characteristics of children who developed VDS: higher peak lactate (6.2 +/- 2.6 vs. 3.0 +/- 2.1 mmol/L; p = 0.0002), higher peak serum blood urea nitrogen (18.5 +/- 4.6 vs. 15.6 +/- 7.2 mg/dL; p = 0.04), lower urine output (1.7 +/- 0.8 vs. 2.6 +/- 0.2 mL/kg/hr; p = 0.04), and fewer intensive care unit free days (14.9 +/- 9.0 vs. 21.1 +/- 7.2 days; p = 0.01). Univariate predictors for the development of post-CPB VDS included children who had heart transplantation (HT) (relative risk [RR], 9.8; 95% confidence interval [CI], 2.7-35.2) or ventricular assist device (VAD) placed (RR, 17.9; 95% CI, 3.8-84.1), a cardiomyopathy diagnosis (RR, 8.5; 95% CI, 2.3-31), age >12 years (RR, 4.5; 95% CI, 1.2-17.0), CPB time >180 minutes (RR, 7.1; 95% CI, 1.9-26.2), and preoperative ventricular dysfunction (RR, 3.7; 95% CI, 1.0-13.4). By stratified analysis, the only independent predictor for the development of VDS was undergoing HT/VAD. CONCLUSIONS: Post-CPB VDS is uncommon in children. However, children who undergo HT or VAD placement are at high risk for developing post-CPB VDS. Recognition that the overall incidence of post-CPB is low-except in the HT/VAD population-may help guide therapy in the pediatric post-CPB patient.

Multicenter cohort study of in-hospital pediatric cardiac arrest.

OBJECTIVES: 1) To describe clinical characteristics, hospital courses, and outcomes of a cohort of children cared for within the Pediatric Emergency Care Applied Research Network who experienced in-hospital cardiac arrest with sustained return of circulation between July 1, 2003 and December 31, 2004, and 2) to identify factors associated with hospital mortality in this population. These data are required to prepare a randomized trial of therapeutic hypothermia on neurobehavioral outcomes in children after in-hospital cardiac arrest. DESIGN: Retrospective cohort study. SETTING: Fifteen children's hospitals associated with Pediatric Emergency Care Applied Research Network. PATIENTS: Patients between 1 day and 18 years of age who had cardiopulmonary resuscitation and received chest compressions for >1 min, and had a return of circulation for >20 mins. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 353 patients met entry criteria; 172 (48.7%) survived to hospital discharge. Among survivors, 132 (76.7%) had good neurologic outcome documented by Pediatric Cerebral Performance Category scores. After adjustment for age, gender, and first documented cardiac arrest rhythm, variables available before and during the arrest that were independently associated with increased mortality included pre-existing hematologic, oncologic, or immunologic disorders, genetic or metabolic disorders, presence of an endotracheal tube before the arrest, and use of sodium bicarbonate during the arrest. Variables associated with decreased mortality included postoperative cardiopulmonary resuscitation. Extending the time frame to include variables available before, during, and within 12 hours following arrest, variables independently associated with increased mortality included the use of calcium during the arrest. Variables associated with decreased mortality included higher minimum blood pH and pupillary responsiveness. CONCLUSIONS: Many factors are associated with hospital mortality among children after in-hospital cardiac arrest and return of circulation. Such factors must be considered when designing a trial of therapeutic hypothermia after cardiac arrest in pediatric patients.

Noninvasive ventilation during pediatric interhospital ground transport.

OBJECTIVE: We report our use of noninvasive ventilation (NIV) during pediatric interhospital ground transport. METHODS: We retrospectively reviewed transport and hospital records for nonneonatal patients

Increasing amiodarone use in cardiopulmonary resuscitation: an analysis of the National Registry of Cardiopulmonary Resuscitation.

OBJECTIVE: To examine practice patterns of amiodarone use during in-hospital cardiac arrest. This study addresses the changing pattern of amiodarone use over time, following the publication of landmark studies and the inclusion of amiodarone in the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Furthermore, this study examines the impact of hospital and patient specific factors on the use of amiodarone. DESIGN: Retrospective cohort study, using the National Registry for Cardiopulmonary Resuscitation, an international registry of in-hospital resuscitation events. PATIENTS: All patients with an in-hospital ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) event reported to the national registry from January 1, 2000, to July 31, 2005. MEASUREMENTS AND MAIN RESULTS: During the study period, 14,854 of 29,552 (50%) adults (> 18 yrs old) with VF/pVT received an antiarrhythmic drug; 8,883 (60%) of these patients received amiodarone. In adults, amiodarone use for VF/pVT increased from 25% in 2000 to 72% in 2005 (p < .0001). Among children, 270 of 553 (49%) VF/pVT episodes were treated with an antiarrhythmic drug; 108 (40%) of these patients received amiodarone. Adults in institutions with larger intensive care units (> 50 beds) were more likely than those in institutions with smaller intensive care units (< or = 50 beds) to receive amiodarone; the association persisted in multivariable analysis (odds ratio [OR] = 1.825; 95% confidence interval [CI], 1.694-1.966). Thirty five percent of adults with VF/pVT who received amiodarone also received lidocaine, while 67% of children who received amiodarone also received lidocaine (p < .001). It is not possible to determine from the database the order in which medications were administered. CONCLUSIONS: There has been a significant increase in amiodarone use for VF/pVT events over the past 5 yrs. The frequency of amiodarone use in adults correlated positively with the number of intensive care beds. These results suggest that emerging data and national guidelines affect resuscitation practice patterns.