充分的准备是严重过敏反应患者获得良好转归的关键。[44]Simons FE, Ardusso LR, Bilò MB, et al. 2012 Update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy Clin Immunol. 2012;12:389-399.http://www.ncbi.nlm.nih.gov/pubmed/22744267?tool=bestpractice.com在所有患者中,主要目标是心肺支持,并使用肾上腺素缓解严重过敏反应。患者可能表现为不同的严重程度,但因心血管功能衰竭和呼吸障碍可能致死,因此属于最紧急的情况。症状较轻的患者可能会迅速恶化,应密切监测。[1]Lieberman P, Kemp SF, Oppenheimer J, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115(3 Suppl 2):S483-S523.http://www.ncbi.nlm.nih.gov/pubmed/15753926?tool=bestpractice.com
心肺骤停
若患者出现心肺骤停,提示需进行 CPR 及插管通气、静脉 (IV) 补液和静脉肾上腺素给药。
气道管理
由于即使轻微的气道受损也可能会迅速进展为完全的气道阻塞,因此,快速气道评估并给予支持治疗至关重要。如果可能,应由一名技术熟练的麻醉医生或急诊医师进行气道评估和管理。可能有必要实行早期预防性插管甚或环甲软骨切开术,特别是存在吸气相喘鸣时。[1]Lieberman P, Kemp SF, Oppenheimer J, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115(3 Suppl 2):S483-S523.http://www.ncbi.nlm.nih.gov/pubmed/15753926?tool=bestpractice.com呼吸无力可能提示需要通气支持。在所有患者中,均有辅助吸氧指征,除非有禁忌症(例如,如果是晚期 COPD、慢性严重性 CO2 潴留引起呼气动力变得依赖于特定程度的缺氧;对该患者群吸氧可能引起其停止呼吸)。
心脏支持
除非有呼吸短促或呕吐,应使患者处于平坦的仰卧位,抬高腿部(休克体位或头低脚高位)。这会增强静脉回流,从而增加前负荷,增高心输出量。研究已经显示,直立位可能增加死亡风险。[60]Pumphrey RS. Fatal posture in anaphylactic shock. J Allergy Clin Immunol. 2003;112:451-452.http://www.ncbi.nlm.nih.gov/pubmed/12897756?tool=bestpractice.com因血管内容量重新分布至静脉容量血管和间质组织,应进行积极的静脉补液。人体的血管系统由高压、小容量的动脉系统和大量的低压静脉贮血系统构成,后者会在严重过敏反应中扩张,吸收大量的循环血容量。为了补偿这一血管内液体丢失,应静脉给予成人患者 1 L - 2 L 的生理盐水。在肾衰竭或 CHF 患者中,液量过多是一个潜在的并发症。
肾上腺素
所有有全身性反应体征的患者(尤其是低血压、气道肿胀或呼吸困难),均应立即在股前外侧肌肉注射肾上腺素。[61]Singletary EM, Charlton NP, Epstein JL, et al; International Liaison Committee on Resuscitation First Aid Task Force. 2015 American Heart Association and American Red Cross guidelines update for first aid. Circulation. 2015;132(18 suppl 2):s574-s589.http://circ.ahajournals.org/content/132/18_suppl_2/S574#sec-10http://www.ncbi.nlm.nih.gov/pubmed/26473003?tool=bestpractice.com[62]Dinakar, C. Anaphylaxis in children: Current understanding and key issues in diagnosis and treatment. Curr Allergy Asthma Rep. 2012;12:641-649.http://link.springer.com/article/10.1007/s11882-012-0284-1/fulltext.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/22815131?tool=bestpractice.com[63]Sicherer SH, Simons FE. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139:e20164006.http://pediatrics.aappublications.org/content/139/3/e20164006.longhttp://www.ncbi.nlm.nih.gov/pubmed/28193791?tool=bestpractice.com[64]Sicherer SH, Leung DY. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014. J Allergy Clin Immunol. 2015;135:357-367.http://www.ncbi.nlm.nih.gov/pubmed/25662305?tool=bestpractice.com[65]Sheikh A, Simons FE, Barbour V, et al. Adrenaline auto-injectors for the treatment of anaphylaxis with and without cardiovascular collapse in the community. Cochrane Database Syst Rev. 2012;(8):CD008935.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008935.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22895980?tool=bestpractice.com减轻全身症状:较低质量的证据证明,肾上腺素对减轻严重过敏反应的全身症状有效。一项 Cochrane 综述发现,并无有关肾上腺素在严重过敏反应中获益的前瞻性对照试验。不过,根据专家的共识和间接的观察数据,综述的作者以及所有其他指南均建议将肾上腺素作为严重过敏反应的一线治疗药物。[66]Sheikh A, Shehata YA, Brown SG, et al. Adrenaline for the treatment of anaphylaxis: Cochrane systematic review. Allergy. 2009;64:204-212.http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2008.01926.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19178399?tool=bestpractice.com[67]Sheikh A, Shehata YA, Brown-Simon GA, et al. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2008;(4):CD006312.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006312.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/18843712?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。可以根据需要每 5 – 15 分钟重复给药一次。[1]Lieberman P, Kemp SF, Oppenheimer J, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115(3 Suppl 2):S483-S523.http://www.ncbi.nlm.nih.gov/pubmed/15753926?tool=bestpractice.com[3]Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report - second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391-397.http://www.jacionline.org/article/S0091-6749%2805%2902723-5/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/16461139?tool=bestpractice.com[14]Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327:380-384.http://www.ncbi.nlm.nih.gov/pubmed/1294076?tool=bestpractice.com[41]Brown SG. Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis. Curr Opin Allergy Clin Immunol. 2005;5:359-364.http://www.ncbi.nlm.nih.gov/pubmed/15985820?tool=bestpractice.com[68]Pumphrey RS, Stanworth SJ. The clinical spectrum of anaphylaxis in north-west England. Clin Exp Allergy. 1996;26:1364-1370.http://www.ncbi.nlm.nih.gov/pubmed/9027436?tool=bestpractice.com股前外侧优于三角肌肌肉注射或皮下注射。[69]Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001;108:871-873.http://www.ncbi.nlm.nih.gov/pubmed/11692118?tool=bestpractice.com[70]Simons FE, Roberts JR, Gu X, et al. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol. 1998;101:33-37.http://www.ncbi.nlm.nih.gov/pubmed/9449498?tool=bestpractice.com如果患者有严重低血压,亦可考虑静脉给予肾上腺素。有经验的执业医师可以持续输注肾上腺素,并不断调整剂量,直至起效。尚无统一规定的静脉给药方案。肾上腺素对 α-1、β-1 和 β-2 受体的激动作用在逆转严重过敏反应时起关键作用。刺激 α-1 受体会增高血管张力,从而逆转免疫介质所导致的大量血管舒张作用。不过,α-1 刺激也会导致严重高血压,特别是在那些高血压控制不良的患者中。β-1 受体刺激具有正性肌力和变时性作用(即,心率增快和收缩力增强),但过度反应会导致不需要的心动过速,可能对 CAD 患者有害。β-2 激动作用可引起支气管扩张,影响肥大细胞和嗜碱性粒细胞介质的释放。[32]Macdougall CF, Cant AJ, Colver AF. How dangerous is food allergy in childhood? The incidence of severe and fatal allergic reactions across the UK and Ireland. Arch Dis Child. 2002;86:236-239.http://adc.bmj.com/content/86/4/236.longhttp://www.ncbi.nlm.nih.gov/pubmed/11919093?tool=bestpractice.com
在任何严重过敏反应发作后,必须对这些患者开具 2 支肾上腺素自动注射器的处方。[6]Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis: a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115:341-384.http://www.ncbi.nlm.nih.gov/pubmed/26505932?tool=bestpractice.com[71]Medicines and Healthcare products Regulatory Agency. Adrenaline auto-injectors: updated advice after European review. August 2017. https://www.gov.uk (last accessed 18 August 2017).https://www.gov.uk/drug-safety-update/adrenaline-auto-injectors-updated-advice-after-european-review患者或照护者应随时携带这 2 支注射器,并熟悉如何使用。[63]Sicherer SH, Simons FE. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139:e20164006.http://pediatrics.aappublications.org/content/139/3/e20164006.longhttp://www.ncbi.nlm.nih.gov/pubmed/28193791?tool=bestpractice.com对于有严重过敏反应风险的儿童,应开具肾上腺素自动注射器处方,并提供个体化的书面急救计划。[63]Sicherer SH, Simons FE. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139:e20164006.http://pediatrics.aappublications.org/content/139/3/e20164006.longhttp://www.ncbi.nlm.nih.gov/pubmed/28193791?tool=bestpractice.com[72]Wang J, Sicherer SH. Guidance on completing a written allergy and anaphylaxis emergency plan. Pediatrics. 2017;139: e20164005.http://pediatrics.aappublications.org/content/139/3/e20164005.longhttp://www.ncbi.nlm.nih.gov/pubmed/28193793?tool=bestpractice.comAmerican Academy of Pediatrics: allergy and anaphylaxis emergency plan
对接受 β受体阻滞剂治疗的 CAD 患者给予辅助胰高血糖素治疗
CAD 患者可能接受 β受体阻滞剂治疗。药物和基础共病均会使严重过敏反应的治疗更为复杂。β受体阻滞剂会通过限制心率、影响心输出量而削弱肾上腺素的作用。CAD 会限制心力储备,从而会因血管活性介质的释放而加剧低血压。低血压、心动过速和内源性或医源性肾上腺素能物质等应激可通过减少舒张期灌注而引起心肌缺血。胰高血糖素可被用于克服 β 阻滞作用,但由此引起的心动过速对严重 CAD 患者有害。[3]Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report - second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391-397.http://www.jacionline.org/article/S0091-6749%2805%2902723-5/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/16461139?tool=bestpractice.com所以,有必要早期请心脏科医师会诊。
急性期的其他治疗
除了肾上腺素以外,如果患者有持续的呼吸症状(喘鸣、呼吸困难),可使用吸入性 β 激动剂。该类患者应继续辅助吸氧。
H1 和 H2 拮抗剂是常用的药物。减轻持续的呼吸系统症状:较低质量的证据证明,H1-抗阻胺药对减轻虽经肾上腺素治疗仍持续存在的症状有效。最近的一项 Cochrane 综述发现,根据其入选标准,并无有关在严重过敏反应中应用 H1-抗阻胺药的证据。[73]Sheikh A, Ten Broek V, Brown SG, et al. H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review. Allergy. 2007;62:830-837.http://www.ncbi.nlm.nih.gov/pubmed/17620060?tool=bestpractice.com[74]Sheikh A, Ten Broek VM, Brown-Simon GA, et al. H1-antihistamines for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2007:(1):CD006160.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006160.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17253584?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。血清组胺水平于严重过敏反应早期达到顶峰,此后快速回复至基线,但会持续存在严重的身体损伤。[10]Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107:191-193.http://www.ncbi.nlm.nih.gov/pubmed/11150011?tool=bestpractice.com[75]Brown SG. Anaphylaxis: clinical concepts and research priorities. Emerg Med Australas. 2006;18:155-169.http://www.ncbi.nlm.nih.gov/pubmed/16669942?tool=bestpractice.com[76]Smith PL, Kagey-Sobotka A, Bleecker ER, et al. Physiologic manifestations of human anaphylaxis. J Clin Invest. 1980;66:1072-1080.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC371545/pdf/jcinvest00695-0204.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/6776143?tool=bestpractice.com因起效较慢,抗阻胺药无法阻断急性组胺受体结合后发生的事件。多数抗阻胺药可通过静脉、肌肉内或口服途径给药。口服给药对极轻度反应已经足够。非镇静性抗阻胺药在治疗严重过敏反应方面可能较苯海拉明有一定的优势;不过,由于这些较新型的抗阻胺药(二代)只能通过口服给药,因而应用只限于轻度反应。H1 和 H2 抗阻胺药联用在缓解皮肤症状表现方面更为有效。[77]Lin RY, Schwartz LB, Curry A, et al. Histamine and tryptase levels in patients with acute allergic reactions: an emergency department-based study. J Allergy Clin Immunol. 2000;106:65-71.http://www.ncbi.nlm.nih.gov/pubmed/10887307?tool=bestpractice.com[78]Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004;351:2203-2217.http://www.ncbi.nlm.nih.gov/pubmed/15548781?tool=bestpractice.com例如,应联合雷尼替丁给予苯海拉明。这些药物起效较慢,但对治疗荨麻疹-血管性水肿或瘙痒有用。研究已经显示,联用 H1 和 H2 拮抗剂治疗较单用 H1 拮抗剂治疗更为有效。[1]Lieberman P, Kemp SF, Oppenheimer J, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115(3 Suppl 2):S483-S523.http://www.ncbi.nlm.nih.gov/pubmed/15753926?tool=bestpractice.com
维持治疗
口服或静脉使用皮质类固醇在急性严重过敏反应的治疗中无确定作用,因为其起效缓慢,即使是静脉使用,也需 4-6 小时后起作用。皮质类固醇可以预防双相和延迟反应,因此,可用作急症稳定后的预防性治疗。此治疗是持续性特发性严重过敏反应的首选治疗。既往使用过皮质类固醇的患者,包括哮喘患者,可能会从早期使用全身性皮质类固醇中受益。
基础病因治疗 – 免疫疗法
在严重过敏反应症状和体征缓解后,应致力于治疗过敏反应的基础病因。
免疫治疗是 IgE 介导的过敏患者治疗的主要手段,包括重复给予变应原提取物。免疫治疗的传统和最佳方法是皮下注射剂量逐渐增多的变应原提取物,每周一次,持续数月,之后是每月一次的维持治疗,持续 3 - 5 年。[79]Durham SR. Tradition and innovation: finding the right balance. J Allergy Clin Immunol. 2007;119:792-795.http://www.ncbi.nlm.nih.gov/pubmed/17418659?tool=bestpractice.com[80]Finegold I. Allergen immunotherapy: present and future. Allergy Asthma Proc. 2007;28:44-49.http://www.ncbi.nlm.nih.gov/pubmed/17390757?tool=bestpractice.com停药后,长期获益持续至少 3 - 5 年。长期获益包括症状缓解及新致敏反应的发生减少。再次接触相关变应原时,对药物的需求显著降低。[81]Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998;102:558-562.http://www.ncbi.nlm.nih.gov/pubmed/9802362?tool=bestpractice.com
舌下免疫疗法是另一种免疫治疗选择,主要用于草花粉和豚草花粉诱发的过敏性鼻结膜炎。针对其他种类变应原的应用仍在研究之中。采取发病季节前和发病季节期间或常年用药方案进行持续大约 3 年的治疗。罕见报道全身反应。[82]Enrique E, Pineda F, Malek T, et al. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005;116:1073-1079.http://www.ncbi.nlm.nih.gov/pubmed/16275379?tool=bestpractice.com
毒液免疫治疗是预防昆虫叮咬诱发全身性过敏反应的治疗选择;[83]Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol. 2007;120(suppl 3):S25-S85.http://www.jacionline.org/article/S0091-6749(07)01202-X/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/17765078?tool=bestpractice.com [
]Is there randomized controlled trial evidence to support the use of venom immunotherapy to prevent allergic reactions to insect stings?http://cochraneclinicalanswers.com/doi/10.1002/cca.148/full显示答案 对预防这些全身反应有效率可达 95% - 100%。该类治疗需要由过敏专科医师选择可以从该治疗中获益的患者(通常是对叮咬有既往严重过敏性反应病史并且有毒液特异性 IgE 抗体的患者)、选择毒液种类及给药方案。
虽然免疫治疗有十分明确的疗效和益处,但其也有明显的局限性,特别是在治疗过程中有发生急性过敏反应或过敏性休克的风险。正在探讨新型的方法:特别是其他给药途径,如舌下途径。[84]Passalacqua G, Guerra L, Pasquali M, et al. Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy. Inflamm Allergy Drug Targets. 2006;5:43-51.http://www.ncbi.nlm.nih.gov/pubmed/16613563?tool=bestpractice.com