控制惊厥发作是治疗的首要目标。发现发作时,应避免患儿受到身体伤害。而且,对气道、呼吸及循环状态的评估和支持至关重要。多数发作在数分钟之内自行停止,不需要抗惊厥治疗。应降低体温,以缓解不适。
尽管许多到医院就诊的单纯型热性惊厥患儿得到了适当的治疗,但也有大量患儿的处理基于主治医生的临床经验,从而引致过度检查和过度治疗。[44]Fetveit A. Assessment of febrile seizures in children. Eur J Pediatr. 2008 Jan;167(1):17-27.http://www.ncbi.nlm.nih.gov/pubmed/17768636?tool=bestpractice.com[78]Dunlop S, Taitz J. Retrospective review of the management of simple febrile convulsions at a tertiary paediatric institution. J Paediatr Child Health. 2005 Dec;41(12):647-51.http://www.ncbi.nlm.nih.gov/pubmed/16398868?tool=bestpractice.com 对于惊厥发作患儿,识别需接受更详细诊断性评估的候选者,临床洞察力始终是最为重要的工具。[79]Kimia AA, Bachur RG, Torres A, et al. Febrile seizures: emergency medicine perspective. Curr Opin Pediatr. 2015 Jun;27(3):292-7.http://www.ncbi.nlm.nih.gov/pubmed/25944308?tool=bestpractice.com 了解幼儿单纯型热性惊厥的模式,这对限制干预措施和安抚家长非常重要。[80]Warden CR, Zibulewsky J, Mace S, et al. Evaluation and management of febrile seizures in the out-of-hospital and emergency department settings. Ann Emerg Med. 2003 Feb;41(2):215-22.http://www.ncbi.nlm.nih.gov/pubmed/12548271?tool=bestpractice.com
首次单纯性热性惊厥发作
感染因素中最多见为病毒感染,因此不需要抗生素治疗。[12]Millichap JG, Millichap JJ. Role of viral infections in the etiology of febrile seizures. Pediatr Neurol. 2006 Sep;35(3):165-72.http://www.ncbi.nlm.nih.gov/pubmed/16939854?tool=bestpractice.com[42]Millichap JJ, Millichap JG. Methods of investigation and management of infections causing febrile seizures. Pediatr Neurol. 2008 Dec;39(6):381-6.http://www.ncbi.nlm.nih.gov/pubmed/19027582?tool=bestpractice.com
对于发热发作导致反复热性惊厥的患者,使用解热药物对预防热性惊厥复发和降低体温无效。[41]Rosenbloom E, Finkelstein Y, Adams-Webber T, et al. Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review of randomized controlled trials and meta-analysis. Eur J Paediatr Neurol. 2013 Nov;17(6):585-8.http://www.ncbi.nlm.nih.gov/pubmed/23702315?tool=bestpractice.com[48]Joint Working Group of the Research Unit of the Royal College of Physicians and the British Paediatric Association. Guidelines for the management of convulsions with fever. BMJ. 1991 Sep 14;303(6803):634-6.http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1671115http://www.ncbi.nlm.nih.gov/pubmed/1932910?tool=bestpractice.com[81]Strengell T, Uhari M, Tarkka R, et al. Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial. Arch Pediatr Adolesc Med. 2009 Sep;163(9):799-804.http://www.ncbi.nlm.nih.gov/pubmed/19736332?tool=bestpractice.com[82]Offringa M, Newton R, Cozijnsen MA, et al. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;(2):CD003031.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003031.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28225210?tool=bestpractice.com 解热药物有助于退热,但吸收不够迅速,不足以影响导致惊厥发作的个体温度阈值以上的温度。[81]Strengell T, Uhari M, Tarkka R, et al. Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial. Arch Pediatr Adolesc Med. 2009 Sep;163(9):799-804.http://www.ncbi.nlm.nih.gov/pubmed/19736332?tool=bestpractice.com
推荐有所不同;布洛芬属于长效药物,通常作为首选的解热药。[83]Purssell E. Treating fever in children: paracetamol or ibuprofen? Br J Community Nurs. 2002 Jun;7(6):316-20.http://www.ncbi.nlm.nih.gov/pubmed/12066066?tool=bestpractice.com
单纯型热性惊厥+(24 小时内抽搐发作一次以上)与单纯型热性惊厥具有相同的良性预后。[84]Mastrangelo M, Midulla F, Moretti C. Actual insights into the clinical management of febrile seizures. Eur J Pediatr. 2014 Aug;173(8):977-82.http://www.ncbi.nlm.nih.gov/pubmed/24477659?tool=bestpractice.com
发热性疾病和既往出现过一次惊厥发作
没有证据表明解热药物在未来热性惊厥预防方面的有效性。[44]Fetveit A. Assessment of febrile seizures in children. Eur J Pediatr. 2008 Jan;167(1):17-27.http://www.ncbi.nlm.nih.gov/pubmed/17768636?tool=bestpractice.com[85]Wilmshurst JM, Gaillard WD, Vinayan KP, et al. Summary of recommendations for the management of infantile seizures: task force report for the ILAE Commission of Pediatrics. Epilepsia. 2015 Aug;56(8):1185-97.http://onlinelibrary.wiley.com/doi/10.1111/epi.13057/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26122601?tool=bestpractice.com
根据美国儿科学会 (AAP) 关于单纯型热性惊厥的指南,不建议在出现发热或癫痫发作活动的首发体征时给予解热药物和口服地西泮,主要由于尽管解热药物有助于散热,但吸收速度慢,不足以降低峰值体温,并且与抗惊厥药相关的潜在毒性,大于与单纯型热性惊厥相关的轻微风险。[49]American Academy of Pediatrics. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008 Jun;121(6):1281-6.http://pediatrics.aappublications.org/content/121/6/1281.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18519501?tool=bestpractice.com 然而,一项系统评价和 Meta 分析得出的结论是,治疗仍存在争议,具体取决于医生的恰当判断和经验。[86]Sardeli C, Tzellos T, Amaniti E, et al. Deciding on the best treatment strategy for recurrent febrile seizures: an evidence-based medicine approach. Rev Clin Pharmacol Pharmacokinet. 2008;22:320-1.[87]Masuko AH, Castro AA, Santos GR, et al. Intermittent diazepam and continuous phenobarbital to treat recurrence of febrile seizures: a systematic review with meta-analysis. Arq Neuropsiquiatr. 2003 Dec;61(4):897-901.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2003000600001&lng=en&nrm=iso&tlng=enhttp://www.ncbi.nlm.nih.gov/pubmed/14762586?tool=bestpractice.com 另一项系统评价得出的结论是,尽管一些抗惊厥药物在预防惊厥复发方面显示出了统计学上的显著获益,但是随着时间的推移,这种获益并不持续存在,并且存在较高的不良事件发生率。[82]Offringa M, Newton R, Cozijnsen MA, et al. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;(2):CD003031.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003031.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28225210?tool=bestpractice.com [
]What are the effects of prophylactic benzodiazepines, barbiturates, and anticonvulsants for management of febrile seizures in children?https://cochranelibrary.com/cca/doi/10.1002/cca.1653/full显示答案 在 1 至 2 年期间预防一次癫痫发作所需的治疗人数为 16 人,而在与其相关的不良事件背景下,这在临床上被认为是不重要的。退热干预对之后的热性惊厥复发率无影响,对于单纯性发热性惊厥,无指征起始长期抗惊厥药物治疗。[85]Wilmshurst JM, Gaillard WD, Vinayan KP, et al. Summary of recommendations for the management of infantile seizures: task force report for the ILAE Commission of Pediatrics. Epilepsia. 2015 Aug;56(8):1185-97.http://onlinelibrary.wiley.com/doi/10.1111/epi.13057/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26122601?tool=bestpractice.com[88]Baumann RJ, Duffner PK; American Academy of Pediatrics. Treatment of children with simple febrile seizures: the AAP practice parameter. Pediatr Neurol. 2000 Jul;23(1):11-7.http://www.ncbi.nlm.nih.gov/pubmed/10963965?tool=bestpractice.com
复杂型热性惊厥
复杂型热性惊厥患者的发作表现为局灶性、长时间(持续>15 分钟)发作,或者 24 小时内出现多次发作。治疗可包括给予布洛芬,直至热退。此外,可经直肠给予地西泮,如果发作持续,可重复给药。另外,尽管患病期间直肠内使用地西泮可以降低热性惊厥复发的风险,但是应该仔细衡量用药的好处和其潜在毒性。[82]Offringa M, Newton R, Cozijnsen MA, et al. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;(2):CD003031.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003031.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28225210?tool=bestpractice.com[89]Hirabayashi Y, Okumura A, Kondo T, et al. Efficacy of a diazepam suppository at preventing febrile seizure recurrence during a single febrile illness. Brain Dev. 2009 Jun;31(6):414-8.http://www.ncbi.nlm.nih.gov/pubmed/18774250?tool=bestpractice.com 与地西泮直肠给药相比,可优先进行咪达唑仑经颊部给药(如果可行)。与单纯型热性惊厥相比,复杂型热性惊厥的预后相对不确定,2008 年 AAP 治疗单纯型热性惊厥的指南并不适用于复杂型热性惊厥。
复杂型热性惊厥婴幼儿的初步治疗通常在一级或二级水平机构给予,但是,对转诊至儿科医生(二级/三级水平)以进行潜在病因评估,和接受进一步管理,应设置较低的限制。[85]Wilmshurst JM, Gaillard WD, Vinayan KP, et al. Summary of recommendations for the management of infantile seizures: task force report for the ILAE Commission of Pediatrics. Epilepsia. 2015 Aug;56(8):1185-97.http://onlinelibrary.wiley.com/doi/10.1111/epi.13057/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26122601?tool=bestpractice.com[90]Whelan H, Harmelink M, Chou E, et al. Complex febrile seizures: a systematic review. Dis Mon. 2017 Jan;63(1):5-23.https://www.sciencedirect.com/science/article/pii/S001150291630102X?via%3Dihubhttp://www.ncbi.nlm.nih.gov/pubmed/28089358?tool=bestpractice.com
热性惊厥持续状态
热性惊厥持续状态可以被定义为长时间发作或反复发作,发作间期意识不能恢复。 持续时间标准具有争议性,但是在最初使用苯二氮卓类药物失败后应启动全面的癫痫持续状态的治疗方案。[91]Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia. 1999 Jan;40(1):120-2.http://www.ncbi.nlm.nih.gov/pubmed/9924914?tool=bestpractice.com[92]Dodson WE, DeLorenzo RJ, Pedley TA, et al. The treatment of convulsive status epilepticus: recommendations of the Epilepsy Foundation of America’s working group on status epilepticus. JAMA. 1993 Aug 18;270(7):854-9.http://www.ncbi.nlm.nih.gov/pubmed/8340986?tool=bestpractice.com
一项对热性惊厥持续状态患儿进行的前瞻性多中心研究(FEBSTAT 研究)发现,年龄非常小的患儿有长时间发作,最常表现为局灶性、部分性以及时间长,中位持续时间为 68 分钟。[9]Shinnar S, Hesdorffer DC, Nordli DR Jr, et al; FEBSTAT Study Team. Phenomenology of prolonged febrile seizures: results of the FEBSTAT study. Neurology. 2008 Jul 15;71(3):170-6.http://www.ncbi.nlm.nih.gov/pubmed/18525033?tool=bestpractice.com 首次热性惊厥往往即表现为持续状态,急诊科不易识别。 对该研究进一步分析显示三分之一的热性惊厥持续状态是由人单纯疱疹病毒 (HHV-6 和 HHV-7) 感染所致,[16]Epstein LG, Shinnar S, Hesdorffer DC, et al; FEBSTAT Study Team. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study. Epilepsia. 2012 Sep;53(9):1481-8.http://www.ncbi.nlm.nih.gov/pubmed/22954016?tool=bestpractice.com 而且热性癫痫持续状态很少导致脑脊液 (CSF) 细胞计数增多;因此,CSF 细胞计数增多不应考虑热性惊厥持续状态,而应考虑脑膜炎可能。[93]Frank LM, Shinnar S, Hesdorffer DC, et al. Cerebrospinal fluid findings in children with fever-associated status epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT) study. J Pediatr. 2012 Dec;161(6):1169-71.http://www.ncbi.nlm.nih.gov/pubmed/22985722?tool=bestpractice.com
热性惊厥的急救处理。 一项对事故和急诊科长时间热性惊厥(>15 分钟)患儿的前瞻性研究表明,在救护车中直肠给予地西泮的治疗有效率为 11%,而静脉给予地西泮治疗的有效率为 58%。[94]Bassan H, Barzilay M, Shinnar S, et al. Prolonged febrile seizures, clinical characteristics, and acute management. Epilepsia. 2013 Jun;54(6):1092-8.http://www.ncbi.nlm.nih.gov/pubmed/23551165?tool=bestpractice.com
对于癫痫持续状态,应根据当地/国家指南进行管理。
抗惊厥治疗
对惊厥持续时间>5 分钟的患儿进行评估时,需经直肠给予地西泮。之后,如果该发作在 10 分钟之内没有缓解,可再用一次同样剂量。与地西泮直肠给药相比,可优先进行咪达唑仑经颊部给药(如果可行)。
如果两次经直肠给予地西泮无效,则应静脉注射磷苯妥英。
如果发作仍不缓解,则静脉给予地西泮;需要时可在 5 分钟后重复给药一次。 劳拉西泮是另一种治疗选择。
如以上措施无效,则应请专科医生(小儿神经科医生或小儿重症监护医生)按癫痫持续状态的治疗方案进行会诊。
如果医院急救服务不容易获得,则应在癫痫发作最初 5 分钟后尽快直肠内给予地西泮。直肠内给予地西泮是长时间热性惊厥发作,或热性惊厥多次发作的一种紧急处理措施。[2]Shinnar S, Glauser TA. Febrile seizures. J Child Neurol. 2002 Jan;17(suppl 1):S44-52.http://www.ncbi.nlm.nih.gov/pubmed/11918463?tool=bestpractice.com[95]Wheless JW, Clarke DF, Carpenter D. Treatment of pediatric epilepsy: expert opinion, 2005. J Child Neurol. 2005 Dec;20(suppl 1):S1-56.http://www.ncbi.nlm.nih.gov/pubmed/16615562?tool=bestpractice.com[96]O'Dell C, Shinnar S, Ballaban-Gil KR, et al. Rectal diazepam gel in the home management of seizures in children. Pediatr Neurol. 2005 Sep;33(3):166-72.http://www.ncbi.nlm.nih.gov/pubmed/16139730?tool=bestpractice.com 与地西泮直肠给药相比,可优先进行咪达唑仑经颊部给药(如果可行)。
英国和美国分别针对 1 岁和 2 岁以下儿童进行规定,不允许直肠内使用地西泮治疗热性惊厥发作或长时间惊厥发作。 2 岁以下儿童应送往急诊科进行静脉抗惊厥治疗。
热性惊厥复发的预防
最有力的复发预测指标是发生第一次热性惊厥时年龄<14 至 16 个月。[97]Camfield P, Camfield C. Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+). Epileptic Disord. 2015 Jun;17(2):124-33.http://www.ncbi.nlm.nih.gov/pubmed/25917466?tool=bestpractice.com
其他危险因素包括一级亲属中有热性惊厥病史、体温较低,以及初次发作前发热时间较短。[98]Rajadhyaksha S, Shah KN. Controversies in febrile seizures. Indian J Pediatr. 2000 Jan;67(1 suppl):S71-9.http://www.ncbi.nlm.nih.gov/pubmed/11129896?tool=bestpractice.com 体温越高,复发危险性越大。[23]van Stuijvenberg M, Steyerberg EW, Derksen-Lubsen G, et al. Temperature, age, and recurrence of febrile seizure. Arch Pediatr Adolesc Med. 1998 Dec;152(12):1170-5.http://www.ncbi.nlm.nih.gov/pubmed/9856424?tool=bestpractice.com
90% 的复发在两年内发生。
大约 30% 的患儿在随后的发热性疾病中,会出现热性惊厥复发。[99]Sadleir LG, Scheffer IE. Febrile seizures. BMJ. 2007 Feb 10;334(7588):307-11.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796669/http://www.ncbi.nlm.nih.gov/pubmed/17289734?tool=bestpractice.com
预测儿童个体的复发很困难;主要的管理围绕家庭教育。[97]Camfield P, Camfield C. Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+). Epileptic Disord. 2015 Jun;17(2):124-33.http://www.ncbi.nlm.nih.gov/pubmed/25917466?tool=bestpractice.com
出现 2 次或 2 次以上复杂性热性发作,且地西泮治疗无效的患儿,在神经科医生会诊后可能要考虑长期抗惊厥治疗。
一些对照研究发现,间断口服地西泮的预防效果差异很大,[82]Offringa M, Newton R, Cozijnsen MA, et al. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;(2):CD003031.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003031.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28225210?tool=bestpractice.com [
]What are the effects of prophylactic benzodiazepines, barbiturates, and anticonvulsants for management of febrile seizures in children?https://cochranelibrary.com/cca/doi/10.1002/cca.1653/full显示答案 并且通常不建议用于单纯型热性惊厥。[49]American Academy of Pediatrics. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008 Jun;121(6):1281-6.http://pediatrics.aappublications.org/content/121/6/1281.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18519501?tool=bestpractice.com然而,在某些病例中可能有使用指征,例如热性惊厥复发率较高、发生热性惊厥所需的体温阈值较低和/或父母比较焦虑等情况下。[64]Natsume J, Hamano SI, Iyoda K, et al. New guidelines for management of febrile seizures in Japan. Brain Dev. 2017 Jan;39(1):2-9.http://www.ncbi.nlm.nih.gov/pubmed/27613077?tool=bestpractice.com
一项系统评价发现,抗癫痫治疗和退热处理对预防小儿热性惊厥复发没有重要的临床意义。[82]Offringa M, Newton R, Cozijnsen MA, et al. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;(2):CD003031.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003031.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28225210?tool=bestpractice.com 尽管一些间断性抗惊厥治疗,例如口服地西泮、口服氯巴占,或直肠给予地西泮表现出显著的预防作用(与安慰剂或无任何处理相比),但这些益处随时间推移并不能持久,相反还有很高的不良事件发生率。
长期管理需要进行全面的评估和风险分层,为每个孩子设计一个定制计划,关注家庭和日托机构照护者的情况。[100]Gupta A. Febrile seizures. Continuum (Minneap Minn). 2016 Feb;22(1 Epilepsy):51-9.http://www.ncbi.nlm.nih.gov/pubmed/26844730?tool=bestpractice.com