9/16/2018. Recognizing & Managing Seizures in Pediatric TBI. Objectives. Definitions and Epidemiology

Transcription

1 Recognizing & Managing Seizures in Pediatric TBI UW Medicine EMS & Trauma 2018 Conference September 17 and 18, 2018 Mark Wainwright MD PhD Herman and Faye Sarkowsky Professor of Neurology Division Head, Pediatric Neurology University of Washington Objectives To understand the approach to recognition of seizures after TBI Understand the contribution of seizures to secondary neurologic injury after TBI Review the evidence for treatment of seizures and specific treatment approaches Definitions and Epidemiology Impact seizures occur within minutes Early post-traumatic seizures within 7 days Last post-traumatic seizures after 7 days Incidence of PTS in children range from 5.5 to 45% Higher when continuous EEG used for detection Most common risk factors for PTS Younger age; Severe TBI; Subdural Hemorrhage; Inflicted TBI Consensus guidelines for the management of severe TBI support 7 day prophylaxis with an antiepileptic drug Arndt D et al., (2016) J Child Neurol 31:46-56; Keenan et a., (2004) Pediatrics 114:

2 Current Pediatric Recommendations Prophylactic treatment with phenytoin may be considered to reduce the incidence of early posttraumatic seizures (PTS) in pediatric patients with severe TBI. Strength of Recommendation: Weak Quality of Evidence: Low, 2018 update pending Anticonvulsant selection and EEG use is not uniform in the management of severe TBI; pathways reduce this variability Approaches and Decisions in Acute Pediatric TBI (ADAPT) trial 43 Centers; 98% response rate Kurz J et al., Pediatr Crit Care Med 2016; 17: TBI shortens life expectancy particularly in the young More than 40% of adolescents and adults admitted with TBI are dead 13 years later Death rate in younger adults (ages 15-54) 1 year post injury significantly higher compared to community controls (17.4 vs 2.4 per 1000 per year) McMillan T et al., J Neurol Neurosurg Psychiatry 2011;82:931e935 2

3 Long-term mortality is higher in patients with posttraumatic epilepsy Ussk J et al., Neurology 2018;91:e878-e883. Age, abusive mechanism, subdural hemorrhage all contribute to risk for post-traumatic seizures Bennett K et al., (2017) Pediatr Crit Care Med 18:54-63 Abuse or assault most common in young children PTS diagnosed in 543 (25%) of 2,122 cases of severe TBI PTS present in 51% of assault cases vs 21% PTS in other mechanisms Seizures, clinical and electrographic exacerbate acute neurologic injury Clinical Observation In patients with ICH, nonconvulsive seizures are associated with greater mass effect and shift, worsening of NIHSS scores, and trend towards worse outcome (Vespa 2003) Expanding hemorrhages and trend towards worse outcome in another (Claassen 2007) Seizure related herniation in patients with CNS infections (Solomon 2002; Idro 2005) Biochemistry (microdialysis) Seizures cause glutamate spikes on microdialysis, elevated glycerol (membrane breakdown), elevated lactate (Vespa 1998, 2002, 2007) Seizures cause elevations in CBF, ICP (animals and humans), lactate, and metabolic demand Neurophysiology Seizures may trigger peri-injury depolarizations 3

4 18 month old, difficult to awaken after a nap at daycare metabolic acidosis Decerebrate posturing Key mechanisms Open questions Do seizures injure the brain after traumatic brain injury? Clinical seizures, electrographic seizures or both? Does treatment of seizures improve outcome? If so, what is the best treatment? What are the risk factors for and the causes of remote (months to years later)? Can these seizures be prevented by early management after TBI? Which patients should be treated? 4

5 Suspect non-convulsive seizures in children with abusive head trauma Electrographic seizures were entirely nonconvulsive in 8 of 12 children (67%) EEG background (disorganized) and neuroimaging evidence of ischemia were associated with the presence of electrographic seizures (p = 0.05) Hasbani et a., Pediatr Crit Care Med. 2013; 14: Abnormal neuroimaging also increase the risk for long-term development of epilepsy after moderate or severe TBI Keret et al., Seizure 58 (2018) Abnormal neuroimaging is associated with increased risk for seizures after abusive head trauma and risk for poor outcome Seizures were associated with increased risk for death or inpatient rehabilitation Goldstein J et al., Neurocrit Care :63-9 5

6 Seizure severity is associated with hypoxic ischemic injury in abusive head trauma 58 children with severe TBI due to abusive head trauma Electrographic seizures in 51.2% Hypoxic-ischemic injury (by MRI) in 77.4% Dingman A. et al., Pediatric Neurology 82 (2018) Wainwright et al., Ann Neurol :61-67 (perinatal asphyxia) Somera et al., Epilepsia : (early-life seizures) Lloyd et al., J Neuroinflammation :28 (traumatic brain injury) Somera et al., Brain Res : (early life seizures) Blood brain barrier breakdown as mechanism of post-traumatic epilepsy Piao C. et al., Exp Neurol 273 (2015) ; J Cereb Blood Flow Metab

7 25 month old F, now lethargic, most likely from Ativan given in ED Courtesy L. Hirsch MD Courtesy L. Hirsch MD Interim Summary Electrographic seizures are common after moderate and severe TBI Abusive head trauma particularly high risk Need continuous EEG monitoring for 1-2 days Children with a high seizure burden are at risk for hypoxic ischemic injury and need imaging Seizures may worsen neurologic outcome Seizure pathways reduce variability in management 7

8 Cochrane Review Data: Low quality evidence that treatment with an anticonvulsant drug reduces the risk for post-traumatic seizures or posttraumatic epilepsy 10 trials involving 2326 people in 12 published articles Early treatment with a traditional antiepileptic drug (phenytoin or carbamazepine) may reduce the risk of early post traumatic seizures No effect on late seizures or mortality Evidence should interpreted with caution Thompson K, et al., Cochrane Systematic Review - Intervention Version published: 10 August 2015 Prevalence of early clinical seizures despite treatment with levetiracetam is approximately 20% Prevalence in children with TBI who do not receive seizure prophylaxis (20 53%) Rate in children treated with phenytoin (2 15%) Chung M and O Brien N., Pediatr Crit Care Med2016; 17: Pediatric Traumatic Brain Injury Guidelines 18 chapters No standards (level I) 4 guidelines (level II) 14 options (level III) Impact unknown Adherence unknown Barrier factors unknown Adelson et al., 2003 Pediatr Crit Care Med 4(3) Suppl 8

9 2012 Brain Trauma Foundation Update 27 new publications included 25 publications from 2003 guidelines were excluded Hampered by lack of systematic approach to data collection Levels of recommendation changed to Level I Level II, and Level III. New chapters on Neuromonitoring and Neuroimaging Kochanek P et al., 2012 Pediatr Crit Care Med 14(Suppl) S1-82 Harborview Medical Center Pediatric Guidelines Adherence and Outcomes Study (PEGASUS) Objectives and Hypotheses To characterize national variation in adherence to the pediatric TBI guidelines, and to examine the relationship between adherence and outcomes. To identify remediable high priority provider and organizational factors which impact adherence and outcomes To test the hypothesis that adherence to specific clinical indicators during the first 72 hr after admission is associated with improved discharge survival and neurologic outcome 9

10 Inclusion criteria and data abstraction Patients ages 0-17 yr with severe TBI one ICD-9 discharge diagnosis code: , , , , , and Minimum AIS 3 Postresuscitation GCS 8 Alive with ETT in ICU 48 hr after ICU admission Abnormal head CT Trauma history Data abstracted from the EMR and sorted by location Pre-hospital Emergency Department OR ICU 236 subjects identified ages 8.0 (SD, 6.3 yr) Measures of guideline adherence Created 16 clinical indicators Number and type for each location determined a priori 5 PH 5 ED 10 OR 14 ICU For some indicators at time component was included Primary outcome Association of adherence across all locations with mortality and discharge GOS Secondary outcomes Association with the location-specific adherence to indicators Key findings associated with better outcome Maintenance of CPP > 40 mm Hg in the first 72 hr in OR and ICU Avoidance of pre-hospital hypoxia Early nutrition Hyperventilation in the absence of cerebral herniation Associated with mortality in the presence of herniation Vavilla MS et al., Crit Care Med. (2014) 42:

11 6% lower hazard of death for every percentage point increase in adherence Outcomes for children with traumatic brain injury can be improved by implementing a cooperative program of accepted best practice Retrospective study of 123 pediatric patients with severe TBI Primary outcome; rate of categorised discharge disposition before and after introduction of a pediatric neurocritical care program in 2005 Assessed adjusted outcome as a function of initial injury severity Pineda et al., Lancet Neurol Outcomes improved across the range of initial injury severity After PNCP Before PNCP Pineda et al., Lancet Neurol

12 Summary and clinical implications TBI shortens life expectancy, mainly in the young Post-traumatic epilepsy is associated with an increase in mortality Mechanisms are not known Young age, abusive head trauma and subdural hemorrhage all add to risk Treat severe TBI cases empirically with anticonvulsant [phenytoin 20 mg/kg load then 5 mg/kg/day bid or leviteracetam 30 mg/kg loading dose, then maintenance with mg/kg/day Approach seizures as another second insult like hypoxia and hypotension Manage patients with continuous EEG monitoring; don t rely on the neurologic exam to exclude seizures Create a pathway for management of TBI Follow the guidelines and adhere to them Create a seizure pathway Recognizing & Managing Seizures in Pediatric TBI Thankyou Mark Wainwright MD PhD Herman and Faye Sarkowsky Professor of Neurology Division Head, Pediatric Neurology University of Washington 12