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

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

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

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