Jorge Sallent博士等研究结果显示，Synagis可有效地降低呼吸道合胞病毒（RSV）感染高危婴儿的住院率。 结果还表明，按照推荐的每月注射时间用药是治疗成功的关键。对于某些高危患儿，为了预防RSV感染，治疗一个季节以上是有益的。在予Synagis预防的24例患儿中，仅有7例（2.8%）因RSV而入院。这与RSV影响试验所观察的住院率相吻合。 本研究7例住院患儿的4例，没以按上述推荐的方法治疗，在住院前至少有一次没有给药。另3例为在RSV感染的第一季节开始治疗的患儿，这3例患儿在RSV感染的第二季节未再接受Synagis治疗。这提示某些患儿在继之RSV感染的季节里，预防性应用Synagis是有益的。 Alber marchetli博士等的论文《非Palivizumab预防疗法RSV感染婴儿住院费用的观察》的研究结果表明：对因RSV感染入院并接受Synagis预防疗法的少数患儿，其住院费用明显少于非预防疗法患儿的费用。在这项对20例RSV感染住院的前瞻性研究中，有10例入院前Synagis预防疗法，另10例未予Synagis。 接受Synagis 治疗患儿平均住院费用8,492美元、住院期4.1天；而非其疗法的患儿住院费用为15,786美元、住院期6.8天。 其它研究结果亦显示，Synagis可有效的降低RSV高危患儿的住院率。本研究的结论表明：对于少数几例预防用药后仍病毒感染入院的患者，Synagis降低了RSV感染的严重程度，从而降低了医疗费用。 Robetter Hirsch Ｍedimmune博士亦在论文中阐述，“临床实践表明，Synagis可降低高危患儿RSV感染所致的全身并发症”。研究结果还显示,高危患儿预防性用药可大大降低医疗费用。相信这些研究能引起儿科医生对早产儿及其他高危婴儿治疗的高度重视。 Palivizumab is used for: Preventing serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at high risk of RSV disease. Palivizumab is a monoclonal antibody. It works by preventing RSV from reproducing. Do NOT use Palivizumab if: you are allergic to any ingredient in Palivizumab Contact your doctor or health care provider right away if any of these apply to you. Before using Palivizumab : Some medical conditions may interact with Palivizumab . Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you: if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have a bleeding or blood clotting disorder or low blood platelet levels if you are having heart surgery (cardiopulmonary bypass) if you are taking a blood thinner (eg, warfarin) Some MEDICINES MAY INTERACT with Palivizumab . However, no specific interactions with Palivizumab are known at this time. This may not be a complete list of all interactions that may occur. Ask your health care provider if Palivizumab may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine. How to use Palivizumab : Use Palivizumab as directed by your doctor. Check the label on the medicine for exact dosing instructions. An extra patient leaflet is available with Palivizumab . Talk to your pharmacist if you have questions about this information. Palivizumab is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Palivizumab at home, a health care provider will teach you how to use it. Be sure you understand how to use Palivizumab . Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions. Do not use Palivizumab if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged. Continue to use Palivizumab even if you feel well. Do not miss any doses. Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal. If you miss a dose of Palivizumab , contact your doctor right away. Ask your health care provider any questions you may have about how to use Palivizumab . Important safety information: Children, including those who develop RSV, should continue to receive monthly doses of Palivizumab throughout the RSV season (generally November through April in the Northern Hemisphere). The first dose should be given before the RSV season begins. PREGNANCY and BREAST-FEEDING: Palivizumab is not for use in adults. It is not known if Palivizumab can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Palivizumab while you are pregnant. Palivizumab is not indicated for use in breast-feeding mothers. Do not breast-feed while taking Palivizumab . Possible side effects of Palivizumab : All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome: Cough; diarrhea; mild fever; minor pain, redness, swelling, or warmth at the injection site; runny or stuffy nose; upset stomach; vomiting. Seek medical attention right away if any of these SEVERE side effects occur: Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness; muscle weakness or limpness); blue lips or skin (including under the fingernails); ear pain or discharge; fever; irregular heartbeat; stomach pain; unusual bruising or bleeding; wheezing. This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch. If OVERDOSE is suspected: Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center (http://www.aapcc.org), or emergency room immediately. Proper storage of Palivizumab : Palivizumab is usually handled and stored by a health care provider. If you are using Palivizumab at home, store Palivizumab as directed by your pharmacist or health care provider. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Palivizumab out of the reach of children and away from pets. General information: If you have any questions about Palivizumab , please talk with your doctor, pharmacist, or other health care provider. Palivizumab is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. This information is a summary only. It does not contain all information about Palivizumab . If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider. 美国儿科学会细支气管炎诊治指南(二) 6a:应评价患儿脱水情况及是否能口服补液(X级)。 6b:不推荐常规进行胸部理疗(B级)。 仅有轻度呼吸窘迫的患儿(特别是进食未受影响者),给予密切观察即可。呼吸频率>60~70次/分的患儿(特别是鼻分泌物增多者),进食往往会受到影响。呼吸困难患儿可出现鼻翼扇动、三凹征、呼吸相哮鸣音和呼气相延长,误吸的危险也增加。因呼吸窘迫不能安全进食者应给予静脉补液。液体潴留会导致抗利尿激素分泌增加并出现相应的症状,此时应及时调整治疗方案。 细支气管炎可伴有气道水肿和气道上皮细胞脱落至气道中,从而导致肺过度充气。有时也可出现肺不张,但肺不张并非该病的特征性表现。一项Cochrane系统评价对3项观察胸部理疗对细支气管炎住院患儿疗效的随机对照研究(RCT)进行了分析,结果并未发现胸部理疗有明显的临床疗效。 建议7 7a:先前体健的患儿若脉搏容积血氧饱和度(SpO2)降至90%以下,则为氧疗指征;若SpO2持续低于90%,则应通过足够的氧疗使SpO2升至90%或以上;若患儿的SpO2≥90%且进食良好,仅有轻微呼吸窘迫,则可停用氧疗(D级)。 7b:若患儿临床状况改善,则无需持续监测SpO2(D级)。 7c:对于有明显血流动力学异常的心肺疾病史或早产史的患儿,在准备停用氧疗时应给予密切监测(B级)。 虽然健康婴儿的SpO2可一过性降至89%以下,但一般都在95%以上。罹患细支气管炎时,气道水肿和上皮细胞脱落导致通气血流比(V/Q)失调,氧合指标[包括SpO2和动脉血氧分压(PaO2)]下降。 脉氧监测因其安全、方便等优点在临床得到广泛应用。临床医师应了解氧离曲线的特征,即当SpO2>90%时,即使PaO2明显升高,SpO2也仅能获得轻度增加,而相反,当SpO2<90%时,PaO2轻微下降就会导致SpO2明显下降。问题由此产生:如何单纯依据SpO2来判断细支气管炎患儿是否应住院治疗或给予氧疗? 临床研究及氧离曲线的特点均提示,当SpO2≥90%(海平面呼吸室内空气)时,吸氧所能提供的益处有限,尤其是对于没有呼吸窘迫和进食困难的患儿;由于发热、酸中毒和血红蛋白病等因素可使氧离曲线右移,因此存在这类危险因素的患儿应维持较高的SpO2。 早产儿、低出生体重儿、支气管肺发育不良患儿或有明显血流动力学异常的先天性心脏病患儿易发展成重症疾病而需住院治疗,应给予特别关注。这些患儿基础氧合及其对抗肺部炎症的能力往往都很差,导致低氧更为严重和持续,因此在给予和停用氧疗时尤应慎重。 建议8 8a:CLD、早产儿(<35周)或先天性心脏病患儿可给予帕利珠单抗(palivizumab)预防治疗(A级)。 8b:帕利珠单抗用药方案为每次15 mg/kg肌注,1次/月,连用5个月,多始于每年的11月或12月(C级)。 AAP感染疾病委员会在其2006年报告中推荐这样使用帕利珠单抗: 1. 在6个月以内因慢性肺病(CLD)接受过治疗(氧疗、支气管扩张剂、利尿剂或皮质类固醇治疗)的早产儿,在2岁以内,在呼吸道合胞病毒(RSV)流行季节前应预防性使用帕利珠单抗。 2. 胎龄≤32周的早产儿即使没有CLD,也可从帕利珠单抗预防治疗中获益。对这部分婴幼儿,需考虑的主要因素包括出生时的胎龄以及RSV流行季节开始时的月龄。帕利珠单抗预防治疗可使≤28周早产儿在第一个RSV流行季节(无论在该流行季节期间其月龄如何)中获益。29~32周早产儿在<6个月时接受帕利珠单抗预防治疗,疗效较好。 3. 尽管有研究表明,帕利珠单抗预防治疗可降低32~35周早产儿的住院危险,但考虑到治疗费用,故大多数专家推荐,严重感染高危儿和在RSV流行季节开始时月龄<6个月者应接受帕利珠单抗预防治疗。流行病学证据显示,存在下列危险因素者为严重感染高危儿:入托者,有学龄年龄同胞者,接触环境空气污染物者,存在气道先天异常者,或存在严重神经肌肉疾病者。至少存在2种危险因素的32~35周早产儿才应考虑给予预防治疗。高危婴幼儿应避免暴露于烟草烟雾。许多研究表明,母乳喂养可抵抗多种病毒感染,但母乳是否可以预防RSV感染尚无统一结论。高危婴幼儿还应避免群居或接触感染者。在RSV流行季节应禁止高危婴幼儿入托,并指导其父母注意手部卫生。所有高危婴幼儿及其接触者都应在6个时开始接受帕利珠单抗预防治疗。 4. 北半球(特别是美国)的RSV流行季节主要为11月至次年3月。目前,尽管可以预测RSV流行季节的出现,但还不能准确预测其严重程度、开始时间、达峰时间和结束时间。同一社区不同年份或同一年份不同社区的RSV感染暴发时间,也各不相同。一般来说,RSV流行季节从11~12月开始,次年1~2月达峰,3月末(有时为4月)结束,持续13~20周。临床研究表明,大部分婴幼儿在第5次肌注帕利珠单抗后,血清帕利珠单抗谷浓度仍持续高于有效保护浓度30天以上,也就是说,帕利珠单抗预防治疗5个月可提供大于20周的保护效应,即使RSV流行季节的起始存在变动,也可以覆盖大部分流行季节。帕利珠单抗用药方案不宜轻易改变,必须充分权衡利弊后方可考虑改变。 5. 合并明显血液动力学异常的≤24个月青紫型或非青紫型先天性心脏病患儿也可从帕利珠单抗预防治疗中获益。是否预防性给予帕利珠单抗,还应根据患儿心血管受损程度决定。接受药物治疗的先天性心脏病患儿、中重度肺动脉高压患儿和青紫型先天性心脏病患儿更易从免疫预防治疗中获益。 2项随机、盲法的安慰剂对照研究共对2789例早产、CLD或先天性心脏病患儿进行了研究,结果显示,帕利珠单抗预防治疗使RSV感染所致住院率降低了39%~78%。上市后研究也显示,帕利珠单抗预防治疗可显著降低住院率。但值得注意的是,帕利珠单抗不能治疗RSV感染。 建议9 9a:洗手是预防RSV院内传播的最重要措施:在与患儿直接接触前后,接触邻近患儿的物体后,以及摘手套后,均应洗手(B级)。 9b:首选以酒精为主的擦手剂,其次为有抗微生物作用的肥皂(B级)。 9c:医师应教育患儿及其家庭成员注意手部卫生(B级)。 应采取措施预防RSV及细支气管炎其他病原体在医疗机构(特别是医院内)的传播。在距患儿病床22英尺(6.7米)的空气中仍可检出RSV RNA。病床、床栏杆、桌面和玩具均可被患儿的分泌物污染。污染物表面病原体的活性和传染性可保持数小时。RSV及其他病毒还可通过看护人员的手传给其他人,因而,医务人员频繁洗手可减少RSV院内传播。美国疾病预防和控制中心(CDC)专门发表了洗手指南。该指南详细介绍了洗手的正确方法。如果手部没有肉眼可见的污染物,指南推荐应使用以酒精为主的擦手剂,也可用有抗微生物作用的肥皂替代。 其他有效的预防措施还包括患儿及家庭成员教育,监测RSV流行季节的开始,应用手套并经常更换以防止手套上微生物的播散,直接接触患儿时穿隔离衣等。至于口罩是否可提供额外的保护,目前还没有得到证实。对RSV感染患儿进行隔离或集中诊治尽管有效但并不切实可行。无论如何,医务人员及家庭成员严格注意手部卫生并进行相关的教育都非常重要。 建议10 10a:婴幼儿应避免暴露于被动吸烟(B级)。 10b:推荐母乳喂养以降低儿童下呼吸道疾病发生危险(C级)。 McConnochie等的研究显示,被动吸烟增加RSV感染危险(OR=3.87)。Strachan等的一项涉及被动吸烟与婴幼儿下呼吸道疾病关系的系统评价显示,父母有一方吸烟时,子女发生下呼吸道疾病的危险增加(OR=1.57),其中以母亲吸烟时的危险更大(OR=1.72)。Stocks等分析了20项关于婴儿肺功能的研究后发现,母亲在妊娠期间和分娩后吸烟的婴儿,其肺功能显著下降,表现为用力呼气流速(FEF)下降约20%,此外其他指标也出现不同程度的异常。父亲吸烟也同样可产生不良影响。 母乳中含有抗RSV的免疫因子,包括IgG、IgA和α干扰素(IFN-α)。母乳还有中和RSV的作用。Pullan等的研究显示,与母乳喂养的婴儿相比,非母乳喂养者的RSV感染住院危险显著升高(OR=2.2)。Downhan等也发现,在115例RSV感染住院患儿中,仅8例(7%)接受母乳喂养,而对照组的母乳喂养率为27%(46/167名)。Bachrach等的一项荟萃分析共纳入了33项研究。这些研究均表明,母乳喂养可保护婴儿免于因下呼吸道疾病而住院。对其中9项研究的汇总分析显示,非母乳喂养者的下呼吸道疾病住院危险高达母乳喂养4个月者的3倍。 建议11 临床医师应详细询问补充及替代药物(CAM)的应用(D级)。 由于证据有限,目前还不推荐应用CAM。但许多家长可能给患儿应用了各种各样的CAM,因此临床医师应详细询问这类药物的使用情况,并权衡其利弊。 该指南对2岁以下婴幼儿细支气管炎的诊断和治疗给出了以循证医学为依据的推荐。细支气管炎是一个临床诊断,无需进行诊断性试验。 目前所应用的多数治疗方法,如支气管扩张剂、皮质类固醇、利巴韦林、抗生素、胸片检查、胸部理疗和CAM,并不能有效改善疾病的临床病程。目前推荐的措施包括合理氧疗并进行血氧监测。应用帕利珠单抗进行特异性预防和一些一般预防措施(特别是洗手)预防院内感染也有一定效果。 在细支气管炎研究方面,仍然存在很多悬而未决的问题。例如,缺乏客观、重复性好且方便在医院、急诊、门诊应用的临床评分方法。再如,由于细支气管炎为一种自限性疾病,因此需要进行大规模的研究才能发现一些细微的预后变化,这就需要进行大规模多中心研究。此外还应进一步研究RSV之外的其他致细支气管炎病毒的快速、经济的测定方法,以及鉴别哪些特定人群能够从支气管扩张剂或皮质类固醇治疗中获益,决定开始氧疗的最适SpO2值,进一步探索新的疗法、RSV疫苗以及剂量更小而费用更低的免疫预防疗法。 Synagis（帕利珠单抗palivizumab）英文说明书 SYNAGIS Generic Name for SYNAGISPalivizumab 50mg/vial, 100mg/vial; pwd for IM inj after reconstitution; liq soln; preservative-free. Legal Classification:Rx Pharmacological class for SYNAGISAntiviral monoclonal antibody (IgG1K). Manufacturer of SYNAGISMedImmune, Inc.   Indications for SYNAGISPrevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease (eg, infants with bronchopulmonary dysplasia or born ≤35 wks gestational age), or children with hemodynamically significant congenital heart disease). Adult dose for SYNAGISNot applicable. Children's dosing for SYNAGISGive by IM injection into anterolateral thigh. 15mg/kg once per month before and during RSV season. Cardiopulmonary bypass: see literature. Divide doses >1mL into 2 inj sites. Precautions for SYNAGISHave epinephrine (1:1000) inj available. Pregnancy (Cat.C). Adverse Reactions for SYNAGISAnaphylaxis, hypesensitivity reactions, upper respiratory infection/symptoms (eg, fever, wheezing), GI disturbances, otitis media, rash, hernia, increased SGOT. How is SYNAGIS supplied? Single-use vials (pwd)—1 Single-use vials (soln)—1 Related Disease: Immunomodulators Respiratory syncytial virus~immunomodulators Related Resources