STATUS EPILEPTICUS. Stabilization Phase. 0-5 minutes. First Line Therapy Phase minutes. Second Line minutes. Therapy Phase.

Transcription

1 STATUS EPILEPTICUS ALGORITHM 1. PHASES OF CLINICAL MANAGEMENT Utilize the Neur IP Status Epilepticus (First Line Orders) and Neur IP Status Epilepticus (Infusin Orders) in Epic t guide anticnvulsant therapy Inclusin criteria: Cntinuus clinical seizure activity Intermittent seizure activity withut a return t clinical baseline between seizures Cnfirmed cntinuus seizure activity n patients underging an EEG Exclusin criteria: Nenates less than 28 days ld Children with diagnsed nn-epileptic events and strng suspicin that events are nn-epileptic in rigin 0-5 minutes Stabilizatin Phase Stabilize patient (airway, breathing, circulatin) Fingerstick bld glucse. Treat if less than 60 mg/dl Attempt IV access and cllect electrlytes, hematlgy, txiclgy screen, anticnvulsant levels (if apprpriate) 5-20 minutes First Line Therapy Phase Administer benzdiazepine, rute based n presence f IV access (refer t First Line Agent Dsing Algrithm) minutes Secnd Line Therapy Phase Administer secnd line agent: fsphenytin, levetiracetam, phenbarbital, r valprate sdium (refer t Secnd Line Agent Dsing Algrithm) minutes Third Line Therapy Phase Nte: Cnsider additinal secnd line agents r benzdiazepines while wrking t initiate cntinuus infusin. Administer cntinuus intravenus agent: midazlam, pentbarbital, ketamine, r prpfl (refer t Third Line Agent Dsing Algrithms) Page 1 f 18

2 ALGORITHM 2. FIRST LINE AGENT DOSING Utilize the Epic Orderset Neur IP Status Epilepticus (First Line Orders) t guide initial anticnvulsant therapy NO Chse ONE f the fllwing: IV Access? YES Chse ONE f the fllwing: Midazlam intramuscular (IM) 0.15 mg/kg (max 10 mg) Lrazepam IV 0.1 mg/kg (max 4 mg) Midazlam intranasal (IN) 0.2 mg/kg ttal (max 10 mg); give 0.1 mg/ kg int EACH nstril Diazepam IV 0.2 mg/kg (max 10 mg) Diazepam rectal gel (PR) 6-12 mnths and weight kg: give 2.5 mg 6-12 mnths and weight 10 kg: give 5 mg 1-5 years ld: give 0.5 mg/kg 6-11 years ld: give 0.3 mg/kg 12 + years ld: give 0.2 mg/kg *Please rund t nearest dsage strength* Page 2 f 18

3 ALGORITHM 3. SECOND LINE AGENT DOSING Utilize the Epic Orderset Neur IP Status Epilepticus (First Line Orders) t guide initial anticnvulsant therapy When advancing t a secnd-line agent: Under mst circumstances, chse ONE f the fllwing secnd line agents Fsphenytin Levetiracetam Phenbarbital Valprate Sdium 20 mg PE/kg (max 1500 mg PE) ver 15 minutes If n effect 10 minutes after infusin is cmpleted, cnsider additinal 10 mg PE/ kg lad 60 mg/kg (max 4500 mg) ver 15 minutes Particularly in yunger infants 20 mg/kg (max 1000 mg) ver 15 minutes If n effect 10 minutes after infusin is cmpleted, cnsider additinal 10 mg/kg lad Particularly in absence status epilepticus 40 mg/kg (max 3000 mg) ver 15 minutes Avid in children less than 2 years ld. If seizures persist minutes after the secnd-line agent finishes infusing: Strngly cnsider advancing t a cntinuus infusin agent t imprve the likelihd f quickly achieving seizure cntrl Cnsult Neurlgy and the PICU Cnsider STAT Extended Inpatient EEG Order Page 3 f 18

4 ALGORITHM 4. CONTINUOUS INFUSION AGENT DOSING Adapted frm Tasker & Vitali (2014) Cntinuus Infusin Therapy Phase: Nte: Cnsult Neurlgy and the PICU The fllwing Cntinuus Infusin Agents shuld be strngly cnsidered if seizures persist minutes after the secnd-line agent has finished infusing. Utilize the Epic Orderset Neur IP Status Epilepticus (Infusin Orders) t guide anticnvulsant therapy. Chse ONE f the fllwing fur ptins fr the cntinuus infusin therapy phase (midazlam, pentbarbital, prpfl, r ketamine) and fllw the assciated treatment and dsing algrithm. A. MIDAZOLAM Page 4 f 18

5 B. PENTOBARBITAL C. PROPOFOL Page 5 f 18

6 D. KETAMINE TABLE OF CONTENTS Algrithm 1. Phases f Clinical Management Algrithm 2. First Line Agent Dsing Algrithm 3. Secnd Line Agent Dsing Algrithm 4. Cntinuus Infusin Agent Dsing Target Ppulatin Backgrund Definitins Initial Evaluatin Clinical Management Labratry Studies Imaging n/a Therapeutics Anticnvulsant Recmmendatins Parent Caregiver Educatin Related Dcuments References Clinical Imprvement Team Page 6 f 18

7 TARGET POPULATION Inclusin Criteria This prtcl shuld be utilized in the fllwing clinical situatins in either inpatient r utpatient settings when applicable, regardless f suspected etilgy: Cntinuus clinical seizure activity Intermittent seizure activity withut a return tward clinical baseline between seizures Cnfirmed cntinuus seizure activity n patients underging an electrencephalgram (EEG) Exclusin Criteria The fllwing grups f patients shuld be excluded frm this prtcl Nenates less than 28 days ld Children with diagnsed nn-epileptic events OR strng suspicin that events are nn-epileptic in rigin BACKGROUND DEFINITIONS Status epilepticus (SE) is ne f the mst cmmn pediatric neurlgical emergencies. Patient age, etilgy, and SE duratin all affect utcme, but nly SE duratin can be mdified with timely administratin f anticnvulsant medicatins. Benzdiazepine receptrs internalize during prlnged seizures, stressing the imprtance f early treatment while the receptr is available t bind the medicatin. In a study f 190 pediatric patients with status epilepticus, a lnger time t benzdiazepine and nn-benzdiazepine administratin were assciated with a lnger duratin f status epilepticus. 1 Utilizing a standardized clinical pathway may help reduce status epilepticus duratin and mrbidity. The American Academy f Neurlgy has established a quality measurement set that recmmends that patients start third-line therapy within 60 minutes f seizure nset r arrival t the emergency department (ED). 4 Definitins Status epilepticus - a cntinuus seizure lasting 5 minutes r tw r mre discrete seizures between which there is incmplete recvery f cnsciusness. 2 Refractry status epilepticus - Clinical r electrgraphic seizures that persist after an adequate dse f an initial benzdiazepine and a secnd apprpriate anti-seizure medicatin. 3 INITIAL EVALUATION The initial evaluatin f the patient presenting in status epilepticus centers n prmpt stabilizatin f the patient, cessatin f seizure activity, and determinatin f the etilgy f the patient s seizures. Stabilizatin Patients presenting in status epilepticus are at high risk fr cardipulmnary failure secndary t nging seizure activity, as well as side effects f antiepileptic medicatins. Careful adherence t resuscitatin and PALS prtcls is paramunt. Initiate cntinuus pulse ximetry and cardiac mnitring, as well as frequent bld pressure mnitring. Assess xygenatin and respiratry effrt. Administer xygen as needed fr hypxia if respiratry effrt is adequate. Frequent reassessment fr hyppnea r apnea shuld be cmpleted fr all patients n xygen, especially thse with escalating xygen requirements. Cnsider intubatin if patient has signs f respiratry cmprmise, including hyppnea/apnea, irregular respiratry effrt, pr secretin management, and/r cmprmised cugh r gag reflexes. Cnsider cntinuus capngraphy. Obtain IV access. If unable t btain PIV, cnsider IO placement. Page 7 f 18

8 Histry and Physical If caregivers are present r the medical recrd can be quickly reviewed, determine if the patient has a knwn histry f seizures r epilepsy. The mst cmmn etilgies f status epilepticus in patients with knwn seizures r epilepsy include breakthrugh seizure, missed medicatin, and illness. Thus, patients with knwn seizures may nt require extensive wrk-up; hwever, wrk-up shuld always be tailred t the individual patient. Cmmn etilgies f new nset status epilepticus include hypglycemia, electrlyte disturbances, drug/txin ingestin, intracranial pathlgy (such as intracranial hemrrhage, strke, r tumr), CNS infectin, febrile status epilepticus, and undiagnsed epilepsy. Screen fr fever, illness, dehydratin, expsure, ingestin, trauma, r fall. If signs r symptms nted n physical exam and histry are suggestive f a prvking etilgy, cnsider the evaluatins belw. Diagnstic Wrk-Up fr Status Epilepticus Hypglycemia ANY patient is at risk fr hypglycemia (including patients with knwn epilepsy). Check bld glucse and crrect if less than 60 mg/dl (5 ml/kg [max: 150 ml per dse f 10% dextrse (D10)]). If patient is n ketgenic diet, crrect bld glucse nly if less than 40 mg/dl with 2.5 ml/kg D10. Cnsider empiric Thiamine 20 mg/kg/day IV prir t dextrse if at risk fr nutritinal deficiencies. Electrlyte disturbances Particularly imprtant t cnsider fr infants and patients with recent vmiting, diarrhea, r pr PO intake. Check basic r cmprehensive metablic panel (BMP r CMP) t assess fr hypnatremia r hypcalcemia. Crrect hypnatremia carefully (gal t increase sdium t 120 meq/l quickly then slwly increase by less than 8-12 meq/l/day) t mitigate risk f cerebral pntine demyelinatin. Administer hypertnic saline (3 ml/kg f 3% saline). Repeat plasma sdium, and if remains lw and the patient is seizing, repeat the dse. Crrect hypcalcemia with calcium glucnate (r calcium chlride if central venus line (CVL) in place) and cnsider assessing fr cncurrent hypmagnesemia. Drug/txin ingestin Cnsider in patients with pssible expsure. Bld gas t evaluate fr acidsis, which culd suggest ingestin UTx, salicylate, acetaminphen, and ethanl levels EKG Sub-therapeutic anticnvulsant levels Cnsider in patients with a histry f epilepsy n anticnvulsant therapy. Cnsider checking anticnvulsant drug levels in situatins where cmpliance may be a cncern (e.g. emesis, teenager, etc.). If levels are subtherapeutic, discuss dsage change with the pediatric neurlgy team. Intracranial pathlgy Strngly cnsider fr infants, patients with cncern fr head trauma r significant fall, patients with fcal seizure, patients with fcal neurlgic deficits, patients with signs f increased intracranial pressure, and patients with pr return t baseline after cessatin f seizure activity. Cnsider emergent nn-cntrast head CT r rapid MRI brain prtcl. Page 8 f 18

9 Additinal Diagnstic Cnsideratins Electrencephalgram (EEG) T assess fr subclinical seizure activity and assist in medicatin titratin, an EEG shuld be rdered STAT after failure f the secnd-line agent r if the patient is paralyzed befre clinical seizure activity stps (ex. Fr rapid sequence intubatin). Place the Extended Inpatient EEG Order in EPIC and page Neurlgy ICU resident/app r Neurlgy n-call resident t ntify f need fr STAT EEG. The Neurlgy team is respnsible fr triaging EEGs and will cntact the EEG technlgists Hwever, d nt pstpne imaging r lumbar puncture fr the EEG unless directed t d s by the Neurlgy r ICU team. Infectius evaluatin if patient is febrile r clinical histry is suggestive f infectin: Obtain CBC with differential, BMP, CRP, ESR, 2 bld cultures, serum save and freeze, urinalysis with micrscpy and urine culture, respiratry multiplex PCR pathgen panel. If head CT/MRI des nt shw signs f elevated ICP, cnsider btaining CSF (cerebrspinal fluid) via lumbar puncture (LP) r requesting neursurgery t tap shunt. Obtain fur tubes f CSF (vlume in furth tube will be used fr infectius disease testing). Obtain serum glucse at same time as LP. CSF studies shuld include cell cunt with differential, glucse, prtein, and bacterial culture. Cnsider CSF meningitis/encephalitis multiplex PCR panel (MEP; select autmatic rder due t cncern fr encephalpathy/encephalitis). MEP includes HSV testing. In patients with CNS hardware, cnsider requesting micrbilgy lab t btain specialized CSF bacterial cultures t detect slw-grwing bacteria (i.e., P. acnes). If new-nset status epilepticus with fever OR high suspicin fr CNS infectin: Recmmend Infectius Disease cnsultatin t direct further diagnstic wrk-up and treatment based n expsures/risk factrs. 6 Cnsider empiric antibitics (meningitic dses) and acyclvir while abve testing is pending. Maintain adequate hydratin and mnitr renal functin clsely when starting anti-micrbials with risk f nephrtxicity (such as acyclvir, vancmycin, ceftriaxne). Sme antibitics, such as cefepime and flurquinlnes, may decrease seizure threshld and induce nn-cnvulsive status epilepticus in sme patients. 7 This shuld be cnsidered when chsing antibitic cverage r evaluating the underlying etilgy f status epilepticus in patients n antibitic therapy. If the patient is temperature cntrlled r n pentbarbital infusin, surveillance bld cultures are recmmended every 24 hurs. Cnsider urinalysis if indwelling catheter with culture is suggestive f infectin, and tracheal aspirate if change in secretins and/r respiratry status. Metablic evaluatin Cnsider the fllwing, as indicated by histry and physical exam: LFTs, ammnia, anticnvulsant levels, urine/serum txiclgy screens Metablic screen (lactate, pyruvate, creatinine kinase, serum amin acids, urine rganic acids) Cmprehensive CSF studies (lactate, pyruvate, amin acids, neurtransmitter metablites) culd be cnsidered. Cnsider empiric Pyridxine mg IV fr infants and yung children, ideally administered while patient is n ceeg. Physician must stay with patient during and fr 10 minutes after administratin in case f apnea/cma. Check serum AASA level t assess fr pyridxine-dependent epilepsy (nte: AASA level is NOT affected by pyridxine supplementatin). Page 9 f 18

10 Other cnsideratins Autimmune serum and CSF labs (Serum: Encephalpathy autimmune evaluatin panel thrugh May (ENCES), TSH, anti-tpo, anti-thyrglbulin, ESR, CRP, prcalcitnin, ANA panel, ligclnal bands. CSF: Encephalpathy autimmune evaluatin panel thrugh May (ENCEC), ligclnal bands, pening pressure, freeze and hld remainder) culd be cnsidered. Further imaging with full brain MRI (fr example, seizure prtcl) as indicated. Obtain STAT review f utside films by radilgy; radilgy t page and discuss with PICU and/r Neurlgy team when reviewed. CLINICAL MANAGEMENT Supprtive Care Gals PICU admissin is warranted in the setting f hemdynamic instability, impending respiratry failure, r refractry SE with need fr third-tier treatment (cntinuus infusin f medicatins). If patient is admitted t the flr and unstable, call the Rapid Respnse Team (RRT). Target seizure cessatin AND reductin f metablic stress n injured cells Critical t: Rapidly address seizures Maintain cerebral perfusin by aviding hyptensin Prevent hyperthermia Deliver adequate energy Maintain safe airway and assure nrmal xygenatin and ventilatin. Intubatin and mechanical ventilatin if GCS 3-8 r rapid decline in GCS r cncern fr lss f airway prtective reflexes. Strngly cnsider pre-emptive intubatin and mechanical ventilatin when cnsidering cntinuus infusin agents Target nrmal perfusin and tissue xygen delivery as measured by physical exam, nrmal lactate, and end rgan functin. Target nrmcapnea (PaCO ) and nrmxia (SpO %). Maintain nrmal systemic and cerebral perfusin. Cerebral autregulatin is frequently impaired during prlnged (>20-30 min) SE. Avid treatment f hypertensin until seizures have stpped. Assure adequate intravascular vlume. Anticipate and quickly treat medicatin-related hyptensin. Target nrmal BP fr age. Avid hyptensin. Be prepared fr hyptensin with cntinuus infusin agents and rder vaspressr(s) t bedside. Arterial line mnitring is indicated if hemdynamics are labile r patient is intubated. Cnsider arterial line when cnsidering inducing pharmaclgical cma t allw fr ptimal mitigatin and treatment f medicatin related hyptensin. Cnsider btaining central venus access when inducing pharmaclgical cma. HOB at 30 - unless etilgy is acute strke, in which case, lay patient flat t imprve cerebral perfusin. Minimize additinal cerebral metablic demands. Target nrmthermia (36 C-37.5 C). Page 10 f 18

11 Cnsider scheduled antipyretics. If using a cling blanket, cntrl shivering per TTM rder set recmmendatin. Refer t the Thermregulatin Targeted Temperature Management PICU Plicy. Optimize fluids, electrlytes and nutritin. Target nrmal serum sdium cncentratin ( mml/l). Target nrmal serum glucse cncentratin ( mg/dl). Target euvlemia. Treat hypvlemia. Avid treating hypervlemia until the patient has been hemdynamically stable fr 6 hurs (nt requiring additinal fluid resuscitatin r increases in vasactive agents) and risk f cerebral hypperfusin has been determined t be minimal. Target early enteral nutritin via nas-enteric feeding tube with gal t initiate enteral feeds within 48 hurs f admissin. THERAPEUTICS - ANTICONVULSANT RECOMMENDATIONS **Please refer t the EPIC Ordersets Neur IP Status Epilepticus (First-Line Orders) and Neur IP Status Epilepticus (Infusin Orders) t guide anticnvulsant therapeutics fr SE** Nte: Prmpt administratin is the mst critical factr. At this time, there is n evidence t suggest ne treatment ptin ver anther fr any agent. Chice f agent may depend n availability t begin medicatin in a timely manner, patient s hme medicatins, hemdynamic instability, and prvider r institutinal experience. Cnsider cntacting Neurlgy t discuss treatment ptins if there is uncertainty abut hw t prceed. First-Line Agents Refer t the First-Line Agent Dsing Algrithm Benzdiazepines are mst effective when administered within the first 5-10 minutes f seizure activity, befre GABA receptrs have internalized. Chse ONE f the fllwing ptins: Lrazepam IV: 0.1 mg/kg (max 4 mg) administered ver 2 minutes. A secnd dse can be administered if the seizure persists beynd 3-5 minutes after the first dse. Diazepam IV: 0.2 mg/kg (max 10 mg) administered ver 2 minutes. A secnd dse can be administered if the seizure persists beynd 3-5 minutes after the first dse. If IV access is nt available, chse ONE f the fllwing ptins: Midazlam intramuscular: 0.15 mg/kg (max 10 mg) Midazlam intranasal: 0.2 mg/kg ttal (max 10 mg ttal), give 0.1 mg/kg int EACH nstril Diazepam rectal gel (PR): 6-12 mnths and weight 5 t 9.9 kg, give 2.5 mg mnths and weight 10 kg, give 5 mg. 1-5 years ld, give 0.5 mg/kg; 6-11 years ld, give 0.3 mg/kg; 12+ years ld, give 0.2 mg/kg. Please rund t nearest available dsage strength. Available as 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg Secnd-Line Agents Refer t the Secnd-Line Agent Dsing Algrithm When advancing t a secnd line agent, cnsider cnsulting Neurlgy and infrming the ICU that their care may be needed. Under mst circumstances, chse ONE f the fllwing secnd-line agents. If seizures persist minutes after the secnd-line agent finishes infusing, strngly cnsider advancing t a cntinuus infusin agent (thirdline agent) t imprve the likelihd f quickly achieving seizure-cntrl. Fsphenytin IV lad: Fsphenytin IV is available in all CHCO lcatins. Fsphenytin is dsed in mg f Phenytin Equivalents (PE). Page 11 f 18

12 20 mg PE/kg (max 1500 mg PE), infused ver 15 minutes. If seizure persists 10 minutes after initial dse is cmplete, then can cnsider additinal 10 mg PE/kg lad (ver 10 minutes) r, if unable t administer secnd blus, escalate t third-line agent. Check serum ttal phenytin cncentratins 2-3 hurs after the lad. Levetiracetam IV lad: Levetiracetam IV is available in all CHCO lcatins. 60 mg/kg (max 4500 mg), infused ver 15 minutes. If seizure persists 10 minutes after dse cmplete, then advance t third-line agent. Phenbarbital IV lad, particularly in yunger infants Phenbarbital IV is available in all CHCO lcatins. 20 mg/kg (max 1000 mg), infused ver 15 minutes. If seizure persists 10 minutes after dse is cmplete, then can cnsider additinal 10 mg/kg lad (infused ver 10 minutes) r, if unable t administer secnd blus, escalate t third-line agent. Check serum phenbarbital cncentratin 2-3 hurs after the lad. Valprate sdium IV Lad (Depacn the IV frm f enteral medicatins such as Depakte, Depakene, divalprate sdium, r valpric acid) - particularly effective in absence status epilepticus Valprate sdium is available in all CHCO lcatins except West campus. 40 mg/kg (max 3000 mg), infused ver 15 minutes. Avid in children less than 2 years ld, unless mitchndrial DNA plymerase gamma (POLG1) gene status is knwn. May cause hyperammnemia. If seizure persists 10 minutes after dse cmplete, then advance t third-line agent. Third-Line Agents Refer t the Cntinuus Infusin Agent Dsing Algrithm Refractry status epilepticus will typically nt respnd t alternative secnd-line agents. The fllwing Cntinuus Infusin Agents shuld be strngly cnsidered if seizures persist minutes after the secnd-line agent has finished infusing. Additinal secnd-line agents may be administered while preparing t initiate a cntinuus infusin agent. Titrate cntinuus infusin dsing t cessatin f electrgraphic seizures r burst suppressin. In mst cases, hurs f seizure cntrl is recmmended prir t slw withdrawal f cntinuus infusin. T avid versuppressin, uptitrate cntinuus infusin sparingly (e.g., increase the infusin rate with every ther blus). Reassess every tw hurs fr versuppressin (less than 1 burst per page n EEG, unless suggested by Neurlgy). If versuppressed, decrease the infusin rate by 10-20%. Hyptensin and respiratry failure are cmmn and shuld be anticipated. If in the Netwrk f Care (NOC) r admitted t a nn-icu hspital flr, evaluate the need fr transfer prir t initiating a third-line agent. Midazlam infusin: Midazlam is available in all CHCO lcatins. Administer a 0.1 mg/kg IV blus (ver 2 minutes) and then begin cntinuus infusin at 0.1 mg/kg/hr. Reassess efficacy every 5-30 mins. If seizures persist, then repeat blus 0.1 mg/kg IV (ver 2 minutes) and uptitrate infusin by 0.1 mg/kg/hr t a max rate f 2 mg/kg/hr. T avid versuppressin, uptitrate cntinuus infusin sparingly (e.g. by 0.1 mg/kg/hr every ther blus). Page 12 f 18

13 While there is n published limit/maximum t the midazlam dse, a rate f greater than 50 mg/hur wuld seem excessive and may suggest the need t utilize a different agent. Can give additinal 0.1 mg/kg bluses as needed fr breakthrugh seizures. In chrts f pediatric patients, initial midazlam lading dses range mg/kg and mean midazlam infusin rates range mg/kg/hr. 8 Hwever, when targeting EEG (vs clinical) endpints, higher dses, up t 2 mg/kg/hr have been used. In adults, a mean effective midazlam infusin rate f 0.48 mg/kg/hr is reprted. 9 Cnsider mving t an alternative infusin if n respnse is present with midazlam abve 1 mg/kg/hr. Pentbarbital infusin: Pentbarbital is nt available in Netwrk f Care lcatins. Administer a 2-5 mg/kg IV blus (ver 15 minutes) and then begin cntinuus infusin at 0.5 mg/kg/hr. Reassess efficacy every 30 minutes. If seizures persist, then reblus in aliquts f 1-2 mg/kg (infused ver minutes). T avid versuppressin, uptitrate cntinuus infusin sparingly (fr example, by 0.5 mg/kg/hr every 60 minutes) t a max rate f 5 mg/kg/hr. Can give additinal 1-2 mg/kg bluses as need fr breakthrugh seizures. Administratin f repeated, small blus dses f pentbarbital is the mst effective strategy t achieve seizure cessatin r burst suppressin during cma inductin and can facilitate the use f lwer infusin rates/dses, which may avid versuppressin and unnecessarily prlnged cma. 10,11 Prpfl infusin (Nte that blus dses are in mg/kg and infusin rates are in mcg/kg/min): Prpfl is nt available in Netwrk f Care lcatins. Administer a 2 mg/kg IV blus (ver 1-5 minutes) and then begin cntinuus infusin at 20 mcg/kg/min. Reassess efficacy every 5-30 minutes. If seizures persist, then reblus with mg/kg IV and uptitrate infusin by mcg/kg/min t a max rate f 67 mcg/kg/min. Can give additinal mg/kg bluses as needed fr breakthrugh seizures. Prpfl-assciated hyptensin is dse dependent and mre likely when administering larger r repeated blus dses. If a patient arrives frm an utside institutin apprpriately cntrlled n prpfl, cnsider cntinuing fr up t 24 hurs r at least until EEG is placed and seizure rescue medicatin plan is determined. T minimize risk f prpfl infusin syndrme: Infusin duratin shuld be as shrt as pssible, and the dse shuld nt exceed 67 mcg/kg/min. 12 If mre than 24 hurs required, then need t assess risk/benefit rati and infrm parents/guardians. Serial bld gas mnitring may be helpful t mnitr fr a develping metablic acidsis as an early indicatin f pssible prpfl infusin syndrme. Refer t the hspital prpfl infusin plicy fr additinal infrmatin. Ketamine infusin: Ketamine is available in all CHCO lcatins. Administer a 2 mg/kg IV blus (ver 5 minutes) and then begin cntinuus infusin at mg/kg/hr. Reassess efficacy every 5-30 minutes. If seizures persist, reblus with 1.5 mg/kg IV and uptitrate infusin by 0.5 mg/kg/h t a max rate f 6 mg/kg/hr. Can give additinal 1.5 mg/kg bluses as needed fr breakthrugh seizures. Adjunctive Therapies Can be utilized in parallel with abve treatments and/r in preparatin fr withdrawal f cntinuus infusin agents. Valprate sdium: Page 13 f 18

14 40 mg/kg IV lad (max dse= 3000 mg), infused ver 15 minutes A lading dse may be particularly helpful in patients n valpric acid (Depakte r Depakene) maintenance therapy with subtherapeutic levels. Check serum valprate cncentratin 2-3 hurs after the lad. Can cnsider starting maintenance at 15 mg/kg/day divided q6hurs, 12 hurs after the lad. Avid in children less than 2 years ld unless mitchndrial DNA plymerase gamma (POLG1) gene status is knwn. May cause hyperammnemia. Additinal secnd-line agents (IV lads +/- maintenance dsing) - Levetiracetam, fsphenytin, r phenbarbital. Discuss dsing recmmendatins with Neurlgy team. Lacsamide: 5 mg/kg IV lad (max 300 mg), infused ver 15 minutes Cnsider starting maintenance at 3-5 mg/kg/day divided BID, beginning 12 hurs after the lad. Typical max dse is 10 mg/kg/day. Tpiramate: 5-10 mg/kg enteral lad (max 400 mg), using immediate release prducts Typically start maintenance at 3-5 mg/kg/day divided BID, beginning 12 hurs after the lad. Uptitrate by 2-5 mg/kg/day every 2-7 days t a max f mg/kg/day. May cause a metablic acidsis. Magnesium Sulfate: mg/kg IV (Max 2 grams), infused ver 30 minutes Cnsider fr patients with POLG1 gene mutatins. Additinal therapies, such as the ketgenic diet, inhaled anesthetics, hypthermia, and immune mdulating treatments, are beynd the scpe f this clinical pathway. Cnsideratin fr tapering f cntinuus infusins 1. There are n data n the apprpriate timing r rate f tapering cntinuus infusins in the treatment f refractry r super-refractry status epilepticus. The cnsideratins detailed belw are based n lcal expert cnsensus. 2. Individualized tapering plans shuld be develped by the multidisciplinary care team, including input frm ICU, Neurlgy, and pharmacists. Fr patients with multisystem disease r super-refractry status, input frm ther relevant, invlved subspecialty teams may als be valuable. 3. Factrs t cnsider when creating a tapering plan: Duratin f therapy: prlnged therapy may need a slwer taper schedule. Half-life f cntinuus infusin agent Availability f timely EEG review fr seizure recurrence Clinical factrs that may supprt mre aggressive tapering rate, e.g., severe hyptensin prly respnsive t intrpic agents Previus cntinuus infusin tapering failure(s) Cnfidence that mre lng-term anticnvulsant medicatins and therapeutic interventins ther than the cntinuus infusin have been sufficiently ptimized t mitigate seizure recurrence risk 4. Prir t initiatin f the tapering plan, cntingency plans fr seizure recurrence shuld be develped by the multidisciplinary care team. The cntingency plan shuld address: Page 14 f 18

15 Clinical seizure and EEG endpints that may be used t guide adjustments t the tapering rate and/r cessatin f the tapering attempt Specific therapeutic escalatin shuld seizures recur (e.g., whether t give additinal intermittently dsed anticnvulsant medicatins, increase/resume the same cntinuus infusin, change t different cntinuus infusin, etc.) 5. The fllwing tapering schedules are meant as a guide and shuld be individualized in the cntext f the abve cnsideratins: a. Midazlam decrease 0.1 mg/kg/hur every 1-3 hurs b. Pentbarbital decrease 1 mg/kg/hur every 1-3 hurs c. Ketamine decrease 1 mg/kg/hur every 1-3 hurs d. Prpfl decrease by 50% fr 1-3 hurs then discntinue. 6. While tapering cntinuus infusin agents, the EEG shuld be reviewed fllwing each weaning step and befre prceeding with the next step. 7. Gd planning and clear cmmunicatin f individualized patient care gals amng all multidisciplinary team members, including bedside nursing, and with the patient s family, is critical during this prcess. PARENT CAREGIVER EDUCATION Fllw up A child wh had a status epilepticus incident is at risk fr experiencing status epilepticus again in the future. Discuss seizure first-aid and seizure precautins with the patient/family. Cnsider prviding caregivers with the fllwing handut: New Seizure Safety Schl Patient Statin English and Spanish. Cnsider prviding caregivers with the fllwing handut: Hme Therapy fr Seizures: Using Intranasal Midazlam Therapy - English r Spanish. Cnsider prviding caregivers with a Seizure Actin Plan and a seizure rescue medicatin at the time f discharge. Page 15 f 18

16 REFERENCES 1. Lddenkemper T, Sanchez Fernandez I, Jacksn MC, Abend NS, Arya R, Brentn JN, et al. Factrs assciated with status epilepticus duratin in children. American Epilepsy Sciety; Philadelphia Brphy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines fr the evaluatin and management f status epilepticus. Neurcritical care. 2012;17(1): Abend NS, Lddenkemper T. Pediatric status epilepticus management. Current pinin in pediatrics. 2014;26(6): Glauser T, Shinnar S, Glss D, Alldredge B, Arya R, Bainbridge J, et al. Evidence-Based Guideline: Treatment f Cnvulsive Status Epilepticus in Children and Adults: Reprt f the Guideline Cmmittee f the American Epilepsy Sciety. Epilepsy currents / American Epilepsy Sciety. 2016;16(1): Tasker RC, Vitali SH. Cntinuus infusin, general anesthesia and ther intensive care treatment fr uncntrlled status epilepticus. Current pinin in pediatrics. 2014;26(6): Tunkel AR, Glaser CA, Blch KC, Sejvar JJ, Marra CM, Rs KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ; Infectius Diseases Sciety f America. The management f encephalitis: clinical practice guidelines by the Infectius Diseases Sciety f America. Clin Infect Dis Aug 1;47(3): Grill MF, Maganti RK. Neurtxic effects assciated with antibitic use: management cnsideratins. Br J Clin Pharmacl Sep; 72(3): Wilkes R, Tasker RC. Intensive care treatment f uncntrlled status epilepticus in children: systematic literature search f midazlam and anesthetic therapies. Pediatr Crit Care Med Sep; 15(7): Ulvi H, Yldas T, Müngen B, Yigiter R. Cntinuus infusin f midazlam in the treatment f refractry generalized cnvulsive status epilepticus. Neurl Sci Oct;23(4): Krishnamurthy KB, Drislane FW. Depth f EEG suppressin and utcme in barbiturate anesthetic treatment fr refractry status epilepticus. Epilepsia Jun;40(6): Schreiber JM1, Gaillard WD. Treatment f refractry status epilepticus in childhd. Curr Neurl Neursci Rep Apr;11(2): Crnfield DN, Tegtmeyer K, Nelsn MD, Milla CE, Sweeney M. Cntinuus prpfl infusin in 142 critically ill children. Pediatrics Dec;110(6): Page 16 f 18

17 CLINICAL IMPROVEMENT TEAM MEMBERS Kevin Chapman, MD Neurlgy Ricka Messer, MD/PhD Neurlgy Pam Reiter, PharmD Clinical Pharmacy Kim Bennett, MD Pediatric Intensive Care Amy Clevenger, MD Pediatric Intensive Care Sarah Mellin, MD Emergency Medicine Sarah Nickels, PhD Clinical Effectiveness REVIEWED BY THE FOLLOWING EXPERTS Kevin Messacar, MD Hspital Medicine and Pediatric Infectius Diseases Suchitra Ra, MD Resident, Hspital Medicine Samuel Dminguez, MD Pediatric Infectius Diseases Leigh Anne Bakel, MD Hspital Medicine Irina Tpz, MD Emergency Medicine Catherine Orendac, MD Emergency Medicine Derrek Massanari, MD Emergency Medicine APPROVED BY Pharmacy & Therapeutics Cmmittee May 4, 2017 Clinical Pathways and Measures Review Cmmittee May 15, 2017 MANUAL/DEPARTMENT Clinical Pathways/Quality ORIGINATION DATE LAST DATE OF REVIEW OR REVISION May 15, 2017 May 15, 2017 APPROVED BY Medical Directr, Clinical Effectiveness REVIEW REVISION SCHEDULE Scheduled fr full review n May 15, 2021 Clinical pathways are intended fr infrmatinal purpses nly. They are current at the date f publicatin and are reviewed n a regular basis t align with the best available evidence. Sme infrmatin and links may nt be available t external viewers. External viewers are encuraged t cnsult ther available surces if needed t cnfirm and supplement the cntent presented in the clinical pathways. Clinical pathways are nt intended t take the place f a physician s r ther health care prvider s advice, and is nt intended t diagnse, treat, cure r prevent any disease r ther medical cnditin. The infrmatin shuld nt be used in place f a visit, call, cnsultatin r advice f a physician r ther health care prvider. Furthermre, the infrmatin is prvided fr use slely at yur wn risk. CHCO accepts n liability fr the cntent, r fr the cnsequences f any actins taken n the basis f the infrmatin prvided. The infrmatin prvided t yu and the actins taken theref are prvided n an as is basis withut any warranty f any kind, express r implied, frm CHCO. CHCO declares n affiliatin, spnsrship, nr any partnerships with any listed rganizatin, r its respective directrs, fficers, emplyees, agents, cntractrs, affiliates, and representatives. Page 17 f 18

18 Page 18 f 18