依据世界卫生组织(WHO)和其他区域具体部门的指南,登革热感染的治疗主要是支持性治疗,没有特定的抗病毒治疗可用于登革热感染。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf[9]Teixeira MG, Barreto M. Diagnosis and management of dengue: clinical review. BMJ. 2009 Nov 18;339:b4338.http://www.ncbi.nlm.nih.gov/pubmed/19923152?tool=bestpractice.com[56]Ministry of Health, Sri Lanka. Guidelines on management of dengue fever and dengue haemorrhagic fever in children and adolescents: revised and expanded edition. November 2012 [internet publication].http://www.epid.gov.lk/web/images/pdf/Publication/gmdfca12.pdf[73]Centers for Disease Control and Prevention. Clinical guidance: dengue virus. September 2014 [internet publication].http://www.cdc.gov/dengue/clinicalLab/clinical.html[74]Ashley EA. Dengue fever. Trends Anaesth Crit Care. 2011;1:39-41. 针对登革热,唯一公认的治疗方式是的维持和补充充足的水分,和针对DHF和DSS的补液疗法。 在登革热流行地区,疑似感染登革热患者应在特定医院进行隔离。
早期诊断和最佳临床处理可减少相关的发病率和死亡率。 误诊,延误治疗,药物使用不当(例如,非甾体抗炎药)和外科干预都是有害的。 教育公众识别登革热感染早期症状、相关的体征以及何时寻求医疗建议,是诊断和治疗的关键。
感染严重程度
根据感染的严重程度,WHO制定了最常见和实用的治疗方案。[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf 根据临床表现,WHO分类将患者分为1-3组(A,B,或C)。
A 组
具有以下临床特点的患者被归为A组,这些患者可在家休息。
没有警示体征(特别是当高热消退)
能耐受足够量口服液体,排尿至少每6小时一次
接近正常的血细胞计数和血细胞比容
B 组
具有以下特点的患者分为B组;这些患者需要住院:
C 组:
具有以下特点的患者分为C组;这些患者需要紧急医疗干预:
C组患者的处理
这些患者需要紧急医疗干预。 应进行重症监护和输血。 建议尽快给予静脉滴注晶体液和胶体液,根据WHO提供的算法。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf 应尽量估算出患者处于危急阶段的时间,以及之前的体液平衡情况
48 小时总液体量应根据下列公式计算:[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[56]Ministry of Health, Sri Lanka. Guidelines on management of dengue fever and dengue haemorrhagic fever in children and adolescents: revised and expanded edition. November 2012 [internet publication].http://www.epid.gov.lk/web/images/pdf/Publication/gmdfca12.pdf
该公式可用于儿童及成人;然而,儿童和成人患者的补液频率不同,应遵照或咨询当地的治疗方案进行治疗。 儿童的公式应使用理想体重。
目前已有研究报道了其他的补液治疗公式,因此,应遵照或咨询当地的治疗方案进行治疗。 输液速度应根据通常的监测参数进行调节和治疗,通常只需24至48小时,一旦血浆渗漏率下降,治疗的危急阶段结束。[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf
胶体液(如右旋糖酐70或6%的淀粉)较晶体液(如0.9%的生理盐水、林格氏乳酸盐液)无明显临床优势。[75]Dung NM, Day NP, Tam DT, et al. Fluid replacement in dengue shock syndrome: randomized, double-blind comparison of four intravenous fluid regimens. Clin Infect Dis. 1999 Oct;29(4):787-94.http://www.ncbi.nlm.nih.gov/pubmed/10589889?tool=bestpractice.com[76]Ngo NT, Cao XT, Kneen R, et al. Acute management of dengue shock syndrome: randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis. 2001 Jan 15;32(2):204-13.http://www.ncbi.nlm.nih.gov/pubmed/11170909?tool=bestpractice.com[77]Wills BA, Nguyen MD, Ha TL, et al. Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med. 2005 Sep 1;353(9):877-89.https://www.nejm.org/doi/full/10.1056/NEJMoa044057http://www.ncbi.nlm.nih.gov/pubmed/16135832?tool=bestpractice.com WHO指南明确指出何时应该使用胶体液(如顽固性休克和抗晶体复苏)。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf
患者需要全程接受密切监测,包括生命体征、外周灌注、体液平衡、血细胞比容、血小板计数、尿量、体温、血糖、肝功能检测 (LFT)、肾功能、凝血功能和其他器官功能(需要时)。
通常,患者的病情会在数小时补液治疗后稳定。 如果病情仍然不稳定,应考虑到和处理其他原因如代谢性酸中毒,电解质不平衡(例如,低血钙,低血糖),心肌炎,或肝坏死。 如果患者没有改善,红细胞压积下降,应怀疑内出血并立即输血;然而,要谨慎,因为有液体超负荷的危险。 目前的共识是在早期使用胶体液治疗,而针对难治性不稳定的患者给予输血。
过度或过快的液体疗法可导致液体超负荷,引起肺水肿,面部充血,颈静脉压升高,胸腔积液,腹水。 针对这些并发症应限制静脉输液治疗及单次静脉推注速尿,直到患者稳定。
B组患者处理
这些患者需要住院。 应对感染的严重程度进行评估。 如果患者不在早期危急阶段(例如,血浆渗漏),鼓励采取口服补液(例如,成人约2500mL/24小时,或对于儿童需要适应其年龄段的补液量)。 如果无法实现,或患者进入危急阶段(红细胞压积上升,低蛋白血症,血小板减少,白细胞减少症,第三间隙的液体丢失,体位性脉压下降),应根据维持剂量补液(M)+5%液体亏损公式计算补液量,给予0.9%的生理盐水静脉补液(或乳酸林格氏液)。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[56]Ministry of Health, Sri Lanka. Guidelines on management of dengue fever and dengue haemorrhagic fever in children and adolescents: revised and expanded edition. November 2012 [internet publication].http://www.epid.gov.lk/web/images/pdf/Publication/gmdfca12.pdf 胶体液(如右旋糖酐70或6%的淀粉)较晶体液(如0.9%的生理盐水、林格氏乳酸盐液)无明显临床优势。[75]Dung NM, Day NP, Tam DT, et al. Fluid replacement in dengue shock syndrome: randomized, double-blind comparison of four intravenous fluid regimens. Clin Infect Dis. 1999 Oct;29(4):787-94.http://www.ncbi.nlm.nih.gov/pubmed/10589889?tool=bestpractice.com[76]Ngo NT, Cao XT, Kneen R, et al. Acute management of dengue shock syndrome: randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis. 2001 Jan 15;32(2):204-13.http://www.ncbi.nlm.nih.gov/pubmed/11170909?tool=bestpractice.com[77]Wills BA, Nguyen MD, Ha TL, et al. Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med. 2005 Sep 1;353(9):877-89.https://www.nejm.org/doi/full/10.1056/NEJMoa044057http://www.ncbi.nlm.nih.gov/pubmed/16135832?tool=bestpractice.com WHO指南明确指出何时应该使用胶体液(如顽固性休克和抗晶体复苏)。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf
应密切监视患者,包括生命体征、末梢灌注、体液平衡、血细胞比容、血小板计数、尿量、温度、血糖、肝功、肾功能和凝血功能。
A组患者处理
这些患者可以建议在家休息。 鼓励采取口服的液体(例如,成人约2500mL/24小时,或对于儿童需要适应其年龄段的补液量)。 口服补液产品,果汁,和清汤比水更好;然而,建议避免红或棕色液体,因为这些液体在患者呕血时造成混淆。
患者应休息。 发热时可用温水擦拭。 疼痛或发热可用正常剂量的对乙酰氨基酚;然而,应避免非甾体抗炎药,因其可增加出血倾向。
应给予患者有警示症状概述的小册子,如果出现任何警示征象,建议立即返回医院。 应每天进行血细胞计数。
妊娠
妊娠是孕产妇死亡率增高和产前预后不佳的一个危险因素。 剖宫产、先兆子痫、早产、低出生体重和感染垂直传播的发生率也会增加。[38]Pouliot SH, Xiong X, Harille RM, et al. Maternal dengue and pregnancy outcomes: a systemic review. Obstet Gynecol Surv. 2010 Feb;65(2):107-18.http://www.ncbi.nlm.nih.gov/pubmed/20100360?tool=bestpractice.com[39]Paixão ES, Teixeira MG, Costa MDCN, et al. Dengue during pregnancy and adverse fetal outcomes: a systematic review and meta-analysis. Lancet Infect Dis. 2016 Jul;16(7):857-65.http://www.ncbi.nlm.nih.gov/pubmed/26949028?tool=bestpractice.com 然而,一项针对 14 项研究的 Meta 分析发现,目前的证据并未表明产妇感染会增加早产、低出生体重、流产和死产的风险。[41]Xiong YQ, Mo Y, Shi TL, et al. Dengue virus infection during pregnancy increased the risk of adverse fetal outcomes? An updated meta-analysis. J Clin Virol. 2017 Sep;94:42-9.http://www.ncbi.nlm.nih.gov/pubmed/28753531?tool=bestpractice.com 对此类患者密切观察和细心处理很重要。补液建议与非妊娠的成年人一样;然而,应该在公式中使用妊娠前的体重。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[78]Ministry of Health, Sri Lanka. Guidelines on management of dengue fever and dengue haemorrhagic fever in adults: revised and expanded edition. November 2012 [internet publication].http://www.epid.gov.lk/web/images/pdf/Publication/guidelines_for_the_management_of_df_and_dhf_in_adults.pdf
怀孕可引起各种相关的生理变化,如心率变快,血压低,脉压变大,血红蛋白和红细胞压积降低,血小板计数减少,应参照感染第一天的基线参数,随后的结果解释要谨慎。 此外,其他一些发生在妊娠期的情况,如先兆子痫和HELLP综合征,也可能改变实验室检查参数。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[78]Ministry of Health, Sri Lanka. Guidelines on management of dengue fever and dengue haemorrhagic fever in adults: revised and expanded edition. November 2012 [internet publication].http://www.epid.gov.lk/web/images/pdf/Publication/guidelines_for_the_management_of_df_and_dhf_in_adults.pdf
对孕妇检测血浆渗漏(如腹水,胸水)较困难,因此,建议早期使用超声波。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[78]Ministry of Health, Sri Lanka. Guidelines on management of dengue fever and dengue haemorrhagic fever in adults: revised and expanded edition. November 2012 [internet publication].http://www.epid.gov.lk/web/images/pdf/Publication/guidelines_for_the_management_of_df_and_dhf_in_adults.pdf
妊娠期必须鉴别登革热与寨卡病毒感染,因为已知后者能引起新生儿小头畸形。[61]Rasmussen SA, Jamieson DJ, Honein MA, et al. Zika virus and birth defects-reviewing the evidence for causality. N Engl J Med. 2016 May 19;374(20):1981-7.http://www.nejm.org/doi/full/10.1056/NEJMsr1604338http://www.ncbi.nlm.nih.gov/pubmed/27074377?tool=bestpractice.com
儿童
世界卫生组织指南主要是基于儿童人群进行的研究;因此,该管理办法对成人与儿童相似,液体量的计算应按照理想体重。
由于儿童进展为DHF和DSS的趋势正在增加,因此实验室检查如血细胞比容,血小板计数,和尿量应定时监测。
与年长的儿童和成人相比,对非常年幼儿童严重程度评估较难。 婴儿呼吸储备较少并且更容易电解质不平衡和肝功能损害。 血浆渗漏在儿童患者中进展可能更迅速,且对液体复苏反应更快。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1
恢复和出院
可以根据临床参数的改善以及患者的食欲和舒适度来确认恢复。 患者可能会出现利尿现象,此时应注意低钾血症的可能。 如果发生这种情况,应停止静脉输液并给予富钾的液体。 患者也可能在恢复过程中出现皮疹或全身瘙痒。 一旦达到身体舒适,体温正常48小时,血小板计数上升,红细胞压积稳定,患者即可以出院。[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf
辅助治疗
极少需要预防性输注血小板(即使血小板计数非常低),因而不建议,除非有活动性出血。 新鲜冰冻血浆、皮质类固醇、静脉注射免疫球蛋白和抗生素的临床价值存在争议,在推荐使用之前需要更多的证据。[1]World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1[79]Rajapakse S. Corticosteroids in the treatment of dengue illness. Trans R Soc Trop Med Hyg. 2009 Feb;103(2):122-6.http://www.ncbi.nlm.nih.gov/pubmed/18789467?tool=bestpractice.com
一项多中心、开放标签的随机临床试验发现,就预防登革热和血小板减少症成人患者的出血而言,预防性血小板输注加支持性治疗并不优于单独采用支持性治疗,并且实际上可能会导致不良事件(例如,荨麻疹、严重过敏反应、输血相关性急性肺损伤、容量超负荷)。[80]Lye DC, Archuleta S, Syed-Omar SF, et al. Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial. Lancet. 2017 Apr 22;389(10079):1611-8.http://www.ncbi.nlm.nih.gov/pubmed/28283286?tool=bestpractice.com
疾病报告
在登革热流行地区,怀疑或已证实的登革热感染病例应尽快报告给相关部门,以便采取适当的措施,以防止登革热传播。[2]World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. 2009 [internet publication].http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf
外周静脉置管的动画演示
中心静脉置管的动画演示