Impaired echocardiographic left ventricular global longitudinal strain after pediatric cardiac arrest children is associated with mortality.

2023

109936

08/2023

1873-1570

BACKGROUND: Global longitudinal strain (GLS) is an echocardiographic method to identify left ventricular (LV) dysfunction after cardiac arrest that is less sensitive to loading conditions. We aimed to identify the frequency of impaired GLS following pediatric cardiac arrest, and its association with hospital mortality.

METHODS: This is a retrospective single-center cohort study of children <18 years of age treated in the pediatric intensive care unit (PICU) after in- or out-of-hospital cardiac arrest (IHCA and OHCA), with echocardiogram performed within 24 hours of initiation of post-arrest PICU care between 2013 and 2020. Patients with congenital heart disease, post-arrest extracorporeal support, or inability to measure GLS were excluded. Echocardiographic LV ejection fraction (EF) and shortening fraction (SF) were abstracted from the chart. GLS was measured post hoc; impaired strain was defined as LV GLS ≥ 2 SD worse than age-dependent normative values. Demographics and pre-arrest, arrest, and post-arrest characteristics were compared between subjects with normal versus impaired GLS. Correlation between GLS, SF and EF were calculated with Pearson comparison. Logistic regression tested the association of GLS with mortality. Area under the receiver operator curve (AUROC) was calculated for discriminative utility of GLS, EF, and SF with mortality.

RESULTS: GLS was measured in 124 subjects; impaired GLS was present in 46 (37.1%). Subjects with impaired GLS were older (median 7.9 vs. 1.9 years, p < 0.001), more likely to have ventricular tachycardia/fibrillation as initial rhythm (19.6% versus 3.8%, p = 0.017) and had higher peak troponin levels in the first 24 hours post-arrest (median 2.5 vs. 0.5, p = 0.002). There were no differences between arrest location or CPR duration by GLS groups. Subjects with impaired GLS compared to normal GLS had lower median EF (42.6% versus 62.3%) and median SF (23.3% versus 36.6%), all p < 0.001, with strong inverse correlation between GLS and EF (rho -0.76, p < 0.001) and SF (rho -0.71, p < 0.001). Patients with impaired GLS had higher rates of mortality (60% vs. 32%, p = 0.009). GLS was associated with mortality when controlling for age and initial rhythm [aOR 1.17 per 1% increase in GLS (95% CI 1.09-1.26), p < 0.001]. GLS, EF and SF had similar discrimination for mortality: GLS AUROC 0.69 (95% CI 0.60-0.79); EF AUROC 0.71 (95% CI 0.58-0.88); SF AUROC 0.71 (95% CI 0.61-0.82), p = 0.101.

CONCLUSIONS: Impaired LV function as measured by GLS after pediatric cardiac arrest is associated with hospital mortality. GLS is a novel complementary metric to traditional post-arrest echocardiography that correlates strongly with EF and SF and is associated with mortality. Future large prospective studies of post-cardiac arrest care should investigate the prognostic utilities of GLS, alongside SF and EF.

10.1016/j.resuscitation.2023.109936

Resuscitation

37574003

Ketamine for Management of Neonatal and Pediatric Refractory Status Epilepticus.

2022

07/2022

1526-632X

OBJECTIVE: Few data are available regarding the use of anesthetic infusions for refractory status epilepticus (RSE) in children and neonates, and ketamine use is increasing despite limited data. We aimed to describe the impact of ketamine for RSE in children and neonates.

METHODS: Retrospective single-center cohort study of consecutive patients admitted to the intensive care units of a quaternary care children's hospital treated with ketamine infusion for RSE.

RESULTS: Sixty-nine patients were treated with a ketamine infusion for RSE. The median age at onset of RSE was 0.7 years (IQR 0.15-7.2), and the cohort included 13 (19%) neonates. Three patients (4%) had adverse events requiring intervention during or within twelve hours of ketamine administration, including hypertension in 2 patients and delirium in 1 patient. Ketamine infusion was followed by seizure termination in 32 (46%) patients, seizure reduction in 19 (28%) patients, and no change in 18 (26%) patients.

DISCUSSION: Ketamine administration was associated with few adverse events, and seizures often terminated or improved after ketamine administration. Further data are needed comparing first-line and subsequent anesthetic medications for treatment of pediatric and neonatal RSE.

CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the therapeutic utility of ketamine for treatment of RSE in children and neonates.

10.1212/WNL.0000000000200889

Neurology

35817569

Guidance for Cardiopulmonary Resuscitation of Children With Suspected or Confirmed COVID-19.

2022

07/2022

1098-4275

This document aims to provide guidance to healthcare workers for the provision of basic and advanced life support to children and neonates with suspected or confirmed COVID-19. It aligns with the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care while providing strategies for reducing risk of transmission of SARS-CoV-2 to healthcare providers. Patients with suspected or confirmed COVID-19 and cardiac arrest should receive chest compressions and defibrillation, when indicated, as soon as possible. Due to the importance of ventilation during pediatric and neonatal resuscitation, oxygenation and ventilation should be prioritized. All CPR events should therefore be considered aerosol-generating procedures (AGPs). Thus, personal protective equipment (PPE) appropriate for AGPs (including N95 respirators or an equivalent) should be donned prior to resuscitation and high-efficiency particulate air (HEPA) filters should be utilized. Any personnel without appropriate PPE should be immediately excused by providers wearing appropriate PPE. Neonatal resuscitation guidance is unchanged from standard algorithms except for specific attention to infection prevention and control. In summary, healthcare personnel should continue to reduce the risk of SARS-CoV-2 transmission through vaccination and use of appropriate PPE during pediatric resuscitations. Healthcare organizations should ensure the availability and appropriate use of PPE. As delays or withheld CPR increases the risk to patients for poor clinical outcomes, children and neonates with suspected or confirmed COVID-19 should receive prompt, high-quality CPR in accordance with evidence-based guidelines.

10.1542/peds.2021-056043

Pediatrics

35818123

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

2021

2766-2777

2021 11

1528-1167

<p><strong>OBJECTIVE: </strong>This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE).</p>

<p><strong>METHODS: </strong>This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45&nbsp;min from seizure onset and before escalating to non-BZD ASM.</p>

<p><strong>RESULTS: </strong>We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR]&nbsp;=&nbsp;.998, 95% confidence interval [CI] = .997-.999 per minute, p&nbsp;=&nbsp;.01). Patients received BZDs beyond 30 and 45&nbsp;min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30&nbsp;min (IRR&nbsp;=&nbsp;2.43, 95% CI = 1.73-3.46, p&nbsp;&lt;&nbsp;.0001) and beyond 45&nbsp;min (IRR&nbsp;=&nbsp;3.75, 95% CI&nbsp;=&nbsp;2.40-6.03, p&nbsp;&lt;&nbsp;.0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45&nbsp;min compared to continuous SE (IRR&nbsp;=&nbsp;1.44, 95% CI = 1.01-2.06, p&nbsp;=&nbsp;.04). Forty-seven percent of patients (n&nbsp;=&nbsp;94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n&nbsp;=&nbsp;54), 48.1% received additional BZDs at hospital arrival.</p>

<p><strong>SIGNIFICANCE: </strong>Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.</p>

10.1111/epi.17043

Epilepsia

34418087

Periodic and rhythmic patterns in critically ill children: Incidence, interrater agreement, and seizures.

2021

2955-2967

2021 12

1528-1167

<p><strong>OBJECTIVES: </strong>We aimed to determine the incidence of periodic and rhythmic patterns (PRP), assess the interrater agreement between electroencephalographers scoring PRP using standardized terminology, and analyze associations between PRP and electrographic seizures (ES) in critically ill children.</p>

<p><strong>METHODS: </strong>This was a prospective observational study of consecutive critically ill children undergoing continuous electroencephalographic monitoring (CEEG). PRP were identified by one electroencephalographer, and then two pediatric electroencephalographers independently scored the first 1-h epoch that contained PRP using standardized terminology. We determined the incidence of PRPs, evaluated interrater agreement between electroencephalographers scoring PRP, and evaluated associations between PRP and ES.</p>

<p><strong>RESULTS: </strong>One thousand three hundred ninety-nine patients underwent CEEG. ES occurred in 345 (25%) subjects. PRP, ES&nbsp;+&nbsp;PRP, and ictal-interictal continuum (IIC) patterns occurred in 142 (10%), 81 (6%), and 93 (7%) subjects, respectively. The most common PRP were generalized periodic discharges (GPD; 43, 30%), lateralized periodic discharges (LPD; 34, 24%), generalized rhythmic delta activity (GRDA; 34, 24%), bilateral independent periodic discharges (BIPD; 14, 10%), and lateralized rhythmic delta activity (LRDA; 11, 8%). ES risk varied by PRP type (p&nbsp;&lt;&nbsp;.01). ES occurrence was associated with GPD (odds ratio [OR] = 6.35, p&nbsp;&lt;&nbsp;.01), LPD (OR = 10.45, p&nbsp;&lt;&nbsp;.01), BIPD (OR = 6.77, p&nbsp;&lt;&nbsp;.01), and LRDA (OR = 6.58, p&nbsp;&lt;&nbsp;.01). Some modifying features increased the risk of ES for each of those PRP. GRDA was not significantly associated with ES (OR = 1.34, p&nbsp;=&nbsp;.44). Each of the IIC patterns was associated with ES (OR = 6.83-8.81, p&nbsp;&lt;&nbsp;.01). ES and PRP occurred within 6&nbsp;h (before or after) in 45 (56%) subjects.</p>

<p><strong>SIGNIFICANCE: </strong>PRP occurred in 10% of critically ill children who underwent CEEG. The most common patterns were GPD, LPD, GRDA, BIPD, and LRDA. The GPD, LPD, BIPD, LRDA, and IIC patterns were associated with ES. GRDA was not associated with ES.</p>

10.1111/epi.17068

Epilepsia

34642942

Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.

2021

e613-e625

2021 12 01

1529-7535

<p><strong>OBJECTIVES: </strong>To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study with prospectively collected data between June 2011 and January 2019.</p>

<p><strong>SETTING: </strong>Seventeen academic hospitals in the United States.</p>

<p><strong>PATIENTS: </strong>We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p &lt; 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p &lt; 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p &lt; 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p &lt; 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments.</p>

<p><strong>CONCLUSIONS: </strong>Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.</p>

10.1097/PCC.0000000000002786

Pediatr Crit Care Med

34120133

Human Adenovirus 7-Associated Hemophagocytic Lymphohistiocytosis-Like Illness: Clinical and Virological Characteristics in a Cluster of Five Pediatric Cases.

2020

2020 Aug 31

1537-6591

<p><strong>BACKGROUND: </strong>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking.</p>

<p><strong>METHODS: </strong>We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018-2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed.</p>

<p><strong>RESULTS: </strong>All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified two clusters - one related to strains implicated in 2016-2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain.</p>

<p><strong>CONCLUSIONS: </strong>It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.</p>

10.1093/cid/ciaa1277

Clin. Infect. Dis.

32866230

Multisystem Inflammatory Syndrome in Children during the COVID-19 pandemic: a case series.

2020

2020 May 28

2048-7207

<p>We present a series of six critically ill children with Multisystem Inflammatory Syndrome in Children (MIS-C). Key findings of this syndrome include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes.</p>

10.1093/jpids/piaa069

J Pediatric Infect Dis Soc

32463092

Vancomycin Prescribing and Therapeutic Drug Monitoring in Children With and Without Acute Kidney Injury After Cardiac Arrest.

2019

2019 Mar 12

1179-2019

<p><strong>BACKGROUND: </strong>Acute kidney injury (AKI) commonly occurs after cardiac arrest. Those subsequently treated with vancomycin are at additional risk for drug-induced kidney injury.</p>

<p><strong>OBJECTIVE: </strong>We aimed to determine whether opportunities exist for improved drug monitoring after cardiac arrest.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of children aged 30&nbsp;days-17&nbsp;years treated after cardiac arrest in an intensive care unit from January 2010 to September 2014 who received vancomycin within 24&nbsp;h of arrest. Vancomycin dosing and monitoring were compared between those with and without AKI, with AKI defined as pRIFLE (pediatric risk, injury, failure, loss, end-stage renal disease) stage 2-3 AKI at day 5 using Schwartz formula-calculated estimated glomerular filtration rate (eGFR).</p>

<p><strong>RESULTS: </strong>Of 43 children, 16 (37%) had AKI at day 5. Age, arrest duration, median time to first vancomycin dose, and the number of doses before and time to first vancomycin concentration measurement were similar between groups. Children with AKI had higher initial vancomycin concentrations than those without AKI (median 16 vs. 7&nbsp;mg/L; p = 0.003). A concentration was not measured before the second dose in 44% of children with AKI. Initial eGFR predicted day 5 AKI. In children with AKI, the initial eGFR was lower in those with than those without a concentration measurement before the second dose (29&nbsp;mL/min/1.73&nbsp;m [interquartile range (IQR) 23-47] vs. 52 [IQR 50-57]; p = 0.03) but well below normal in both.</p>

<p><strong>CONCLUSIONS: </strong>In children with AKI after cardiac arrest, decreased vancomycin clearance was evident early, and early monitoring was not performed universally in those with low initial eGFR. Earlier vancomycin therapeutic drug monitoring is indicated in this high-risk population.</p>

10.1007/s40272-019-00328-8

Paediatr Drugs

30864056