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778 SECTION VI Pediatric Critical Care Neurologic be limited by the time course over which the pathophysiologic monitoring is enacted For example, the following need to be con­ sidered what processes[.]

778 S E C T I O N V I   Pediatric Critical Care: Neurologic be limited by the time course over which the pathophysiologic monitoring is enacted For example, the following need to be con­ sidered: what processes occur at the time of injury, what are the subsequent epiphenomena of these events, and what are the sec­ ondary factors that are amenable to treatment and altered out­ come?46–52 Mechanisms and occur at the time of injury, and mechanism starts during the interval between the accident and arrival in the ICU, although this mechanism may, in part, be avoid­ able with attention to emergency care and life support Mechanisms and are processes in which treatment that is directed by inten­ sive care monitoring presumably has the potential for altered out­ come (i.e., focal brain tissue shifts and hemodynamic perfusion failure) One important issue therefore is the natural history of brain swelling and local compartment syndrome after severe head injury In persons with a TBI, intracranial hypertension occurs when there is brain swelling or a hematoma that occupies signifi­ cant space In persons with severe TBI and abnormalities shown with CT scans on admission, a greater than 50% chance of raised ICP exists In adults, this complication may occur in persons whose CT scans appear normal, particularly if two of the following three features are present: age older than 40 years, unilateral or bilateral motor posturing, or systolic ABP below 90 mm Hg In children, the occurrence of this complication has been ana­ lyzed in a UK national dataset of all 501 children receiving critical care after sustaining a severe head injury Forsyth et al.35 found that by modeling demographic, acute physiologic, and cranial imaging variables they could derive an empiric decision rule that predicted the development of raised ICP at any point during ICU admission with a sensitivity of 73% and a specificity of 74% (positive predictive value, 82%; negative predictive value, 63%) Overall, raised ICP was present in 25% of those undergoing inva­ sive monitoring Importantly, the decision rule predicted raised ICP in 20% of children not undergoing ICP monitoring Natale et al.53 have shown that the natural history of raised ICP in chil­ dren not requiring surgery after head injury can be as short as days However, not infrequently, it lasts for to 10 days Thus, regarding brain tissue shifts and frontal compartment perfusion failure, the potential of a postinsult therapeutic window exists, which also implies a goal for therapy directed by ICP monitoring Key References Akhondi-Asl A, Vonberg FW, Au CC, Tasker RC Meaning of intracranial pressure-to-blood pressure Fisher-transformed Pearson correlationderived optimal cerebral perfusion pressure: testing empiric utility in a mechanistic model Crit Care Med 2018;46:e1160-e1166 Avery RA, Shah SS, Licht DJ, et al Reference range for cerebrospinal fluid opening pressure in children N Engl J Med 2010;363: 891-893 Davson H, Hollingsworth G, Segal MB The mechanism of drainage of the cerebrospinal fluid Brain 1970;93:665-678 Kochanek PM, Tasker RC, Bell MJ, et al Management of pediatric severe traumatic brain injury: 2019 consensus and guidelines-based algorithm for first and second tier therapies Pediatr Crit Care Med 2019;20:269-279 Lundberg N Continuous recording and control of ventricular fluid pressure in neurosurgical practice Acta Psychiatr Neurol Scand 1960;36(suppl 149):1-193 Payne S Cerebral Autoregulation: Control of Blood Flow in the Brain Switzerland: Springer; 2016 Tasker RC, Salmond CH, Westland AG, et al Head circumference and brain and hippocampal volume after severe traumatic brain injury in childhood Pediatr Res 2005;58:302-308 The full reference list for this chapter is available at ExpertConsult.com e1 References Pickard JD, Czosnyka M, Steiner LA Raised intracranial pressure In: Hughes RAC, ed Neurological Emergencies London: BMJ Pub­ lishing Group; 2003 Davson H, Hollingsworth G, Segal MB The mechanism of drainage of the cerebrospinal fluid Brain 1970;93:665-678 Kashif FM, Verghese GC, Novak V, et al Model-based noninvasive estimation of intracranial pressure from cerebral blood flow velocity and arterial pressure Sci Transl Med 2012;4:129ra44 Fanelli A, Vonberg FW, LaRovere KL, et al Fully automated, real-time, calibration-free, continuous noninvasive estimation of intracranial pressure in children J Neurosurg Pediatr 2019 [Epub ahead of print] Kochanek PM, Tasker RC, Bell MJ, et al Management of pediatric severe traumatic brain injury: 2019 consensus and guidelines-based algorithm for first and second tier therapies Pediatr Crit Care Med 2019;20:269-279 Kochanek PM, Tasker RC, Carney N, et al Guidelines for the man­ agement of pediatric severe traumatic brain injury, third edition: update of the brain trauma foundation guideline Pediatr Crit Care Med 2019;20(3 suppl 1):S1-S82 Robba C, Santori G, Czosnyka M, et al Optic nerve sheath diame­ ter measured sonographically as non-invasive estimator of intracra­ nial pressure: a systematic review and meta-analysis Intensive Care Med 2018;44:1284-1294 Pietrangelo SJ, Lee HS, Sodini CG A wearable transcranial Doppler ultrasound phased array system Acta Neurochir Suppl 2018;126:111-114 Miller JD, Stanek A, Langfitt TW Concepts of cerebral perfusion pressure and vascular compression during intracranial hypertension Prog Brain Res 1972;35:411-432 10 Tasker RC Neurocritical care and traumatic brain injury Indian J Pediatr 2001;68:257-266 11 Payne S Cerebral Autoregulation: Control of Blood Flow in the Brain Switzerland: Springer; 2016 12 Steiner LA, Czosnyka M, Piechnik SK, et al Continuous monitor­ ing of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury Crit Care Med 2002;30:733-738 13 Aries MJ, Czosnyka M, Budohoski KP, et al Continuous determina­ tion of optimal cerebral perfusion pressure in traumatic brain injury Crit Care Med 2012;40:2456-2463 14 Lazaridis C, Smielewski P, Steiner LA, et al Optimal cerebral perfu­ sion pressure: are we ready for it? Neurol Res 2013;35:138-148 15 Lewis PM, Czosnyka M, Carter BG, et al Cerebrovascular pressure reactivity in children with traumatic brain injury Pediatr Crit Care Med 2015;16:739-749 16 Akhondi-Asl A, Vonberg FW, Au CC, Tasker RC Meaning of in­ tracranial pressure-to-blood pressure Fisher-transformed Pearson correlation-derived optimal cerebral perfusion pressure: testing empiric utility in a mechanistic model Crit Care Med 2018;46: e1160-e1166 17 Zweifel C, Lavinio A, Steiner LA, et al Continuous monitoring of cerebrovascular pressure reactivity in patients with head injury Neurosurg Focus 2008;25:E2 18 Bijlenga P, Czosnyka M, Budohoski KP, et al “Optimal cerebral perfusion pressure” in poor grade patients after subarachnoid hemor­ rhage Neurocrit Care 2010;13:17-23 19 Petkus V, et al Association between the outcome of traumatic brain injury patients and cerebrovascular autoregulation, cerebral perfusion pressure, age, and injury grades Medicina 2016;52: 46-53 20 Beqiri E, Smielewski P, Robba C, et al Feasibility of individualized severe traumatic brain injury management using an automated as­ sessment of optimal cerebral perfusion pressure: the COGITATE phase II study protocol BMJ Open 2019;9:e030727 21 Ursino M A mathematical study of human intracranial hydrody­ namics part 1—the cerebrospinal fluid pulse pressure Ann Biomed Eng 1988;16:379-401 22 Ursino M A mathematical study of human intracranial hydrody­ namics part 2—Simulation of clinical tests Ann Biomed Eng 1988; 16:403-416 23 Lundberg N Continuous recording and control of ventricular fluid pressure in neurosurgical practice Acta Psychiatr Neurol Scand 1960;36(suppl 149):1-193 24 Baker RE, Pena JM, Jayamohan J, et al Mechanistic models versus machine learning, a fight worth fighting for the biological commu­ nity? Biol Lett 2018;14:20170660 25 Ngo QN, Ranger A, Singh RN, et al External ventricular drains in pediatric patients Pediatr Crit Care Med 2009;10:346-351 26 Tavakoli S, Peitz G, Ares W, et al Complications of invasive intra­ cranial pressure monitoring devices in neurocritical care Neurosurg Focus 2017;43:E6 27 Fernando SM, Tran A, Cheng W, et al Diagnosis of elevated intra­ cranial pressure in critically ill adults: systematic review and metaanalysis BMJ 2019;366:14225 28 Albeck MJ, Borgesen SE, Gjerris F, et al Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects J Neurosurg 1991;74:597-600 29 Chapman PH, Cosman ER, Arnold MA The relationship between ventricular fluid pressure and body position in normal subjects and subjects with shunts: a telemetric study Neurosurgery 1990;26: 181-189 30 Avery RA, Shah SS, Licht DJ, et al Reference range for cerebrospi­ nal fluid opening pressure in children N Engl J Med 2010;363: 891-893 31 Bales JW, Bonow RH, Buckley RT, et al Primary external ventricu­ lar drainage catheter versus intraparenchymal ICP monitoring: out­ come analysis Neurocrit Care 2019;31:11-21 32 Bennett TD, Riva-Cambrin J, Keenan HT, et al Variation in intra­ cranial pressure monitoring and outcomes in pediatric traumatic brain injury Arch Pediatr Adolesc Med 2012;166:641-647 33 Alkhoury F, Kyriakides TC Intracranial pressure monitoring in children with severe traumatic brain injury: national trauma data bank-based review of outcomes JAMA Surg 2014;149:544-546 34 Bennett TD, DeWitt PE, Greene TH, et al Functional outcome after intracranial pressure monitoring for children with severe trau­ matic brain injury JAMA Pediatr 2017;171:965-971 35 Forsyth RJ, Parslow RC, Tasker RC, et al Prediction of raised intra­ cranial pressure complicating severe traumatic brain injury in chil­ dren: implications for trial design Pediatr Crit Care Med 2008;9: 8-14 36 Bailey BM, Liesemer K, Statler KD, et al Monitoring and predic­ tion of intracranial hypertension in pediatric traumatic brain injury: clinical factors and initial head computed tomography J Trauma Acute Care Surg 2012;72:263-270 37 Chesnut RM, Temkin N, Carney N, et al A trial of intracranialpressure monitoring in traumatic brain injury N Engl J Med 2012;367:2471-2481 38 Chesnut RM Intracranial pressure monitoring: headstone or a new head start The BEST TRIP trial in perspective Intensive Care Med 2013;39:771-774 39 Levin HS, Amparo E, Eisenberg HM, et al Magnetic resonance imaging and computerized tomography in relation to the neurobe­ havioural sequelae of mild and moderate head injuries J Neurosurg 1987;66:706-713 40 Wallesch CW, Curio N, Kutz S, et al Outcome after mild-to-mod­ erate blunt head injury: effects of focal lesions and diffuse axonal injury Brain Inj 2001;15:401-412 41 Sweeney JE Nonimpact brain injury: grounds for clinical study of the neuropsychological effects of acceleration forces Clin Neuropsychol 1992;6:443-457 42 Kotapka MJ, Graham DI, Adams JH, et al Hippocampal pathology in fatal human head injury without high intracranial pressure J Neurotrauma 1994;11:317-324 43 Tate DF, Bigler ED Fornix and hippocampal atrophy in traumatic brain injury Learn Mem 2000;7:442-446 e2 44 Tasker RC, Salmond CH, Westland AG, et al Head circumference and brain and hippocampal volume after severe traumatic brain in­ jury in childhood Pediatr Res 2005;58:302-308 45 Adams JH, Graham DI The relationship between ventricular fluid pressure and the neuropathology of raised intracranial pressure Neuropathol Appl Neurobiol 1976;2:323-332 46 Slawik H, Salmond CH, Taylor-Tavares J, et al Frontal cerebral vulnerability and executive deficits from raised intracranial pressure in child traumatic brain injury J Neurotrauma 2009;26:1891-1903 47 Garth J, Anderson V, Wrennall J Executive function following mod­ erate to severe frontal lobe injury: impact of injury and age at injury Pediatr Rehabil 1997;1:99-108 48 Abu-Judeh HH, Parker R, Singh M, et al SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography Nucl Med Commun 1999; 20:505-510 49 Vinjamuri S, O’Driscoll K Significance of white matter abnormali­ ties in patients with closed head injury Nucl Med Commun 2000;21:645-649 50 Shahlaie K, Boggan JE, Latchaw RE, et al Posttraumatic vasospasm detected by continuous brain tissue oxygen monitoring: treatment with intraarterial verapamil and balloon angioplasty Neurocrit Care 2009;10:61-69 51 Nahed BV, Ferreira M, Naunheim MR, et al Intracranial vasospasm with subsequent stroke after traumatic subarachnoid hemorrhage in a 22-month-old child J Neurosurg Pediatr 2009;3:311-315 52 Ghajar J Traumatic brain injury Lancet 2000;356:923-929 53 Natale JE, Joseph JG, Helfaer MA, et al Early hyperthermia after traumatic brain injury in children: risk factors, influence on length of stay, and effect on short-term neurologic status Crit Care Med 2000;28:2608-2615 e3 Abstract: As intracranial hypertension progresses, changes occur in vital signs, with an elevation of blood pressure, decrease or increase in pulse, and irregularity in the respiratory rhythm These signs, sometimes associated with episodes of decerebrate rigidity, indicate the occurrence of transtentorial herniation—or “coning”—that will lead to death if the process cannot be re­ versed The continuous measurement of intracranial pressure is an essential modality in most brain monitoring systems After a decade of enthusiastic attempts to introduce newer modalities for brain monitoring, the measurement of intracranial pressure remains a robust and only moderately invasive modality Key words: intracranial pressure, pressure reactivity index, cerebral perfusion pressure, electrical analog model 64 Status Epilepticus EDWARD E CONWAY JR AND ROBERT C TASKER PEARLS • A seizure is a paroxysmal central nervous system disorder resulting from excessive hypersynchronous discharge of cortical neurons • Status epilepticus is a common pediatric neurologic emergency that requires rapid recognition and intervention • An operational definition of status epilepticus recommends administration of an antiseizure medication (ASM) after minutes of seizure activity; a predetermined pathway/guideline can expedite management • Management goals include general supportive care, termination of status epilepticus, prevention of recurrence, correction of precipitating causes, and prevention and treatment of potential complications • Common errors include underdosing the initial ASM and delay in advancing to a second-line ASM A single drug should be maximized to a high therapeutic or supratherapeutic level before adding a second or third drug • The longer seizures continue, the more difficult they are to stop with medications Early diagnosis and aggressive intervention for both convulsive and nonconvulsive seizures are essential for successful treatment • Prolonged seizures may cause selective neuronal loss in the hippocampus, cortex, and thalamus, areas rich in glutamate receptors A seizure is a paroxysmal disorder of the central nervous system (CNS) gray matter characterized by an abnormal neuronal discharge associated with a change in function of the patient It results from the excessive hypersynchronous discharge of cortical neurons in the gray matter Factors that occur commonly in the pediatric intensive care unit (PICU) and are known to provoke seizures include fever, hyponatremia, hypoglycemia, hypocalcemia, meningitis, head trauma (accidental or nonaccidental), toxin exposure, ethanol, and many other drugs (both legal and illicit) Seizures are a common pediatric entity and occur in 5% to 8% of children, with the highest risk occurring during infancy and early childhood A seizure must be differentiated from other paroxysmal events, which may include syncope, breath-holding spells, movement disorders, or hyperventilation syndrome a shorter duration of seizure activity based on two ideas: (1) the time at which a seizure should be considered abnormally prolonged (t1) and (2) the time beyond which there is risk of longterm consequences (t2) In this approach, t1 determines the time at which treatment should be considered and t2 determines how aggressively treatment should be implemented to prevent longterm consequences The ILAE committee’s proposal is that t1 5 minutes (based on the mean normal seizure duration standard deviations) and t2 of 30 minutes or longer (based on historical experimental studies and literature) Hence, by definition, this new definition takes account of the fact that the majority of tonic-clonic generalized seizures will resolve within minutes without any medication.1 Thus, it is appropriate that in adults and older children (.5 years old) SE refers to minutes or more of either continuous seizure or two or more discrete seizures between which there is incomplete recovery of consciousness.2,3 Of note, however, this new approach to defining SE lacks supportive pediatric data that would help to make recommendations in children younger than years That said, there is general agreement that seizures continuing for more than minutes should be treated, but there is a concern that overaggressive treatment may lead to avoidable morbidity, such as respiratory depression and transient need for supportive mechanical ventilation For example, the study by DeLorenzo et al (which included 91 children) compared the outcome of patients with seizures lasting 10 to 29 minutes with that of traditionally defined SE (.30 minutes).1 Almost 50% of the seizures in the 10- to 29-minute group stopped spontaneously Definition of Status Epilepticus Status epilepticus (SE) is a common pediatric neurologic emergency estimated to affect between 25,000 to 50,000 children annually; 40% of all instances of SE will occur in children younger than years The incidence of convulsive SE (CSE) in children is approximately 10 to 27 per 100,000 per year The definition of SE has undergone revisions—it was previously defined as a seizure lasting for greater than 30 minutes or recurrent seizures lasting for more than 30 minutes without the patient regaining consciousness between seizures Recent definitions of SE—such as the one from the International League Against Epilepsy (ILAE)—include 779 ... and literature) Hence, by definition, this new definition takes account of the fact that the majority of tonic-clonic generalized seizures will resolve within minutes without any medication.1... drug should be maximized to a high therapeutic or supratherapeutic level before adding a second or third drug • The longer seizures continue, the more difficult they are to stop with medications... abnormally prolonged (t1) and (2) the time beyond which there is risk of longterm consequences (t2) In this approach, t1 determines the time at which treatment should be considered and t2 determines

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