Evidence summary of non-drug prevention and management of febrile neutropenia in cancer patients
LIU Jiahui,LI Xingfeng,CHEN Jiejun LI Xuying,LIU Liping,LI Jinhua
Hunan Cancer Hospital,Hunan 410013 China
Corresponding Author "CHEN Jiejun,E-mail:chenjiejun@hnca.org.cn
Abstract "Objective: To retrieve,evaluate,and integrate the best evidence on non-drug prevention and management of febrile neutropenia in cancer patients. Methods:"Clinical decisions,guidelines,evidence summaries,expert consensus,systematic reviews,and Meta-analyses on non-drug prevention and management of febrile neutropenia in cancer patients were systematically retrieved from relevant guideline websites,databases,and professional association websites in China and abroad. The search period was from database establishment to September 30,2023. Results:"A total of 20 articles were included,including 5 clinical decision-making articles,11 guidelines,and 4 expert consensus articles. A total of 37 pieces of evidence were summarized from 4 aspects: risk assessment,infection prevention and control,health education,and follow-up and monitoring. Conclusions:"The best evidence summarized for non-drug prevention and management of febrile neutropenia in cancer patients could provide evidence-based basis for clinical medical staff,so as to standardize the management of febrile neutropenia in cancer patients.
Keywords""tumor; neutropenia; febrile neutropenia; non-drug management; evidence summary; evidence-based nursing
摘要""目的:檢索、評價并整合有關(guān)腫瘤病人中性粒細胞減少性發(fā)熱的非藥物預防及管理的最佳證據(jù)。方法:系統(tǒng)檢索國內(nèi)外相關(guān)指南網(wǎng)站、數(shù)據(jù)庫以及專業(yè)學會網(wǎng)站中關(guān)于腫瘤病人中性粒細胞減少性發(fā)熱非藥物預防及管理的臨床決策、指南、證據(jù)總結(jié)、專家共識、系統(tǒng)評價及Meta分析等。檢索時限為建庫至2023年9月30日。結(jié)果:共納入20篇文獻,包括臨床決策5篇,指南11篇,專家共識4篇。從風險評估、感染預防與控制、健康教育、隨訪與監(jiān)測4個方面總結(jié)了37條證據(jù)。結(jié)論:總結(jié)的腫瘤病人中性粒細胞減少性發(fā)熱非藥物預防及管理的最佳證據(jù)可為臨床醫(yī)護人員提供循證依據(jù),從而規(guī)范化管理腫瘤病人中性粒細胞減少性發(fā)熱。
關(guān)鍵詞""腫瘤;中性粒細胞減少癥;中性粒細胞減少性發(fā)熱;非藥物管理;證據(jù)總結(jié);循證護理
doi:10.12102/j.issn.2095-8668.2025.05.005
中性粒細胞減少癥是指中性粒細胞計數(shù)≤2.0×109/L,是骨髓抑制性化療藥物引起的主要不良事件,也是骨髓抑制性化療最嚴重的血液學毒性反應。中性粒細胞減少性發(fā)熱(febrile neutropenia,F(xiàn)N)是其最主要的臨床并發(fā)癥,可能引起化療藥物劑量降低、治療延遲或中斷、治療費用增加或抗生素使用等,也可能出現(xiàn)嚴重感染等并發(fā)癥,甚至死亡,給病人家庭、醫(yī)院及社會帶來沉重負擔[1?3]。因此,正確評估中性粒細胞減少癥、FN及感染發(fā)生風險,及時處理相關(guān)并發(fā)癥發(fā)生,對合理的預防和管理FN至關(guān)重要[1,4]。據(jù)報道,因FN引起的并發(fā)癥發(fā)生率為25%~30%,死亡率高達11%[5]。目前,國內(nèi)外已有多項關(guān)于腫瘤病人FN預防、治療或管理的指南及共識文件,但涉及面較廣,以描述臨床藥物預防及抗菌藥物管理等內(nèi)容為主,缺乏針對腫瘤病人FN非藥物預防及管理方案,不利于醫(yī)護人員全面、快速獲取相關(guān)信息。目前,臨床醫(yī)護人員對于腫瘤病人FN的重視程度不高,多基于臨床經(jīng)驗開展預防及管理。因此,本研究總結(jié)有關(guān)腫瘤病人FN非藥物預防及管理的最佳證據(jù),旨在為臨床實踐提供循證參考依據(jù)。
1 資料與方法
1.1 明確循證問題
采用復旦大學循證護理中心制訂的PIPOST模式[6]構(gòu)建腫瘤病人FN非藥物預防及管理的循證問題。目標人群(population,P):腫瘤化療病人。干預方法(intervention,I):腫瘤病人FN的非藥物預防及管理措施,包括感染預防與控制、居家監(jiān)測、健康教育等。證據(jù)應用的專業(yè)人員(professional,P):腫瘤科醫(yī)生和護士。結(jié)局(outcome,O):腫瘤病人FN的發(fā)生情況、與中性粒細胞減少癥相關(guān)不良反應發(fā)生情況、因中性粒細胞減少癥導致的非計劃再入院情況。證據(jù)應用場所(setting,S):醫(yī)院、社區(qū)等。證據(jù)類型(type of evidence,T):指南、專家共識、臨床決策、證據(jù)總結(jié)、系統(tǒng)評價和Meta分析。
1.2 檢索策略
按照“6S”證據(jù)模型,根據(jù)自上而下原則系統(tǒng)檢索UpToDate、BMJ Best Practice、國際指南協(xié)作網(wǎng)、美國國立指南網(wǎng)、澳大利亞喬安娜布里格斯研究所(Joanna Briggs Institute,JBI)循證衛(wèi)生保健中心數(shù)據(jù)庫、the Cochrane Library、PubMed、EMbase、Web of Science、英國國家衛(wèi)生與臨床優(yōu)化研究所(National Institute for Health and Care Excellence,NICE)網(wǎng)站、美國國家綜合癌癥網(wǎng)絡(National Comprehensive Cancer Network,NCCN)、歐洲腫瘤協(xié)會(European Society for Medical Oncology,ESMO)網(wǎng)站、美國臨床腫瘤協(xié)會(American Society of Clinical Oncology,ASCO)網(wǎng)站、世界衛(wèi)生組織(WHO)、中國臨床指南文庫、醫(yī)脈通、萬方數(shù)據(jù)庫、中國生物醫(yī)學文獻數(shù)據(jù)庫"(China Biology Medicine,CBM)、中國知網(wǎng)、維普數(shù)據(jù)庫有關(guān)的臨床決策、指南、系統(tǒng)評價、專家共識等。以“腫瘤/癌癥”“中性粒細胞減少/中性粒細胞減少癥/粒細胞缺乏癥/發(fā)熱性中性粒細胞減少癥”“指南/臨床決策/專家共識/系統(tǒng)綜述/系統(tǒng)評價/Meta分析/循證”為中文檢索詞;以“cancer/oncolog/tumor/neoplasm”"“neutropenia/febrile neutropenia/FN/chemotherapy induced febrile neutropenia/agranulocytosis”"“guidelines/clinical decisions/expert consensus/systematic evaluation/Meta?analysis/summary of evidence”為英文檢索詞。以PubMed為例,檢索式為:(\"neutropenia\"[Title/Abstract]"OR \"febrile neutropenia\"[Title/Abstract]"OR \"FN\"[Title/Abstract]"OR \"chemotherapy induced febrile neutropenia\"[Title/Abstract]"OR \"agranulocytosis\"[Title/Abstract]")"AND (\"cancer\"[Title/Abstract]"OR \"oncology\"[Title/Abstract]"OR \"tumor\"[Title/Abstract]"OR \"neoplasm\"[Title/Abstract]")"AND ("\"guideline\"[Title/Abstract]"OR \"clinical decision\"[Title/Abstract]"OR \"consensus\"[Title/Abstract]"OR \"systematic review\"[Title/Abstract]"OR \"Meta?analysis\"[Title/Abstract]"OR \"summary of evidence\"[Title/ Abstract]")。檢索時限為建庫至2023年9月30日。
1.3 文獻的納入與排除標準
納入標準:1)研究對象為腫瘤化療病人,年齡≥18歲;2)研究內(nèi)容涉及腫瘤病人FN的非藥物預防及管理,包括風險評估、感染預防與控制、監(jiān)測、健康教育等;3)研究類型為指南、臨床決策、專家共識、系統(tǒng)評價和Meta分析等;4)語種為英文或中文。排除標準:1)多個機構(gòu)重復發(fā)表;2)翻譯版本或已更新的文獻;3)內(nèi)容信息不全、文獻質(zhì)量評價未通過。
1.4 文獻的質(zhì)量評價過程
指南質(zhì)量評價采用中文版臨床指南研究與評價系統(tǒng)Ⅱ(appraisal guidelines for research and evaluationⅡ,AGREE Ⅱ)[7];專家共識評價采用JBI循證衛(wèi)生保健中心評價標準(2016版)[8];臨床決策采用證據(jù)總結(jié)的質(zhì)量評價工具評價臨床決策和證據(jù)總結(jié)的質(zhì)量,該工具共10個條目,分別按照“是”“部分是”“否”進行評價[9]。由2名接受過系統(tǒng)循證護理方法與應用研討項目培訓的研究人員獨立進行文獻質(zhì)量評價,并交叉核對,當評價結(jié)果出現(xiàn)分歧時,請相關(guān)領(lǐng)域的權(quán)威循證方法學專家評定。指南由4名研究者評價,意見不統(tǒng)一時,通過協(xié)商或小組討論后裁定。
1.5 證據(jù)提取與匯總
由2名接受過循證護理系統(tǒng)培訓的研究人員對納入文獻逐條提取證據(jù),根據(jù)現(xiàn)有的證據(jù)分類提煉主題并匯總,由其他研究者共同整合結(jié)果進行檢查、核對。證據(jù)整合工作遵循以下原則:1)針對意見一致的內(nèi)容,采用語言表達簡潔、邏輯清晰的推薦意見。2)針對意見互補的內(nèi)容,合并相同主題的推薦意見。3)針對意見不一致的內(nèi)容,遵循高質(zhì)量證據(jù)優(yōu)先、最新發(fā)表文獻優(yōu)先、權(quán)威期刊文獻優(yōu)先的原則進行整合。4)針對意見獨立的內(nèi)容,保留原始表述。采用JBI循證中心證據(jù)預分級標準(2014版)[10],按照納入文獻的研究設計類型將證據(jù)進行等級劃分。將提取的證據(jù)、證據(jù)來源及證據(jù)等級制成表格,邀請具有5年以上循證方法學與臨床實踐經(jīng)驗的3名腫瘤護理專家、2名循證護理學專家參加專家論證會,討論、評價證據(jù),根據(jù)證據(jù)的有效性、可行性、適宜性和臨床意義,確定證據(jù)的推薦強度,A級為強推薦,B級為弱推薦。
2 結(jié)果
2.1 文獻檢索結(jié)果
初步檢索到2 657篇文獻,經(jīng)查重、篩選、質(zhì)量評價后,最終納入20篇文獻[1,3,11?28],其中臨床決策5篇[11?15],指南11篇[3,16?25],專家共識4篇[1,26?28]。文獻篩選流程及結(jié)果見圖1。
2.2 納入文獻的基本特征(見表1)
2.3 文獻質(zhì)量評價結(jié)果
2.3.1 指南的質(zhì)量評價結(jié)果
共納入11篇指南[3,16?25],總體質(zhì)量較高,均符合納入標準,評價結(jié)果見表2。
2.3.2 臨床決策的質(zhì)量評價結(jié)果
納入5篇臨床決策[11?15],各條目的評價結(jié)果均為“是”,總體質(zhì)量高,予以納入。
2.3.3 專家共識的質(zhì)量評價結(jié)果
納入4篇專家共識[1,26?28]。除條目6“所提出的觀點與以往文獻是否有不一致的地方?”評價結(jié)果均為“否”外,其他條目均為“是”,總體質(zhì)量較高,準予納入。
2.4 證據(jù)描述與匯總
本研究共提取了37條腫瘤病人FN非藥物預防及管理的證據(jù),歸納為風險評估、感染預防與控制、健康教育、隨訪與監(jiān)測4個類別,見表3。
3 討論
3.1 重視腫瘤病人FN的風險評估,指導分層管理
對腫瘤病人進行FN風險評估,有助于區(qū)分中性粒細胞減少癥低風險和高風險病人,對病人實施分層管理。證據(jù)1~5匯總了腫瘤病人FN風險評估時機、內(nèi)容、評估工具和風險因素。早期評估和動態(tài)評估是預防FN發(fā)生的關(guān)鍵,應在首次化療前進行FN發(fā)生風險評估,在第1個化療周期結(jié)束后以及每個化療周期前均應進行評價,以確定風險分類和治療目的[1,3,17,20,25]。證據(jù)推薦對所有出現(xiàn)FN的病人評估發(fā)生并發(fā)癥的風險[11?15,20,24,28],可以使用MASCC風險評分、Talcott規(guī)則或CISNE評分工具來評估,CISNE評分工具更適用于實體瘤病人。但鑒于目前用于對FN病人進行風險分層的工具存在各種局限性,應該避免僅基于這些風險評分工具進行評估,在對病人進行治療和決策時,必須考慮與FN相關(guān)的病人因素、治療相關(guān)因素等[29],依據(jù)相關(guān)風險因素進行獨立的、個體化的臨床判斷與決策[3],不能忽視病人偏好、社會環(huán)境和不常見臨床風險因素在內(nèi)的整體臨床評估[30]。
3.2 重點關(guān)注腫瘤病人的感染預防與控制,降低FN風險
由于感染是中性粒細胞減少癥危及生命的重大并發(fā)癥之一,臨床醫(yī)護人員必須具備充足的感染控制和預防知識以及扎實的實踐能力[31]。證據(jù)6~24匯總了一般感染預防與控制的注意事項,為臨床醫(yī)護人員進行腫瘤病人FN非藥物的感染預防與控制提供了循證建議,包括預防隔離措施、環(huán)境管理、感染評估與檢查、體溫監(jiān)測、導管管理和飲食衛(wèi)生等。部分指南或共識就一些一般的感染預防與控制措施達成了一致共識,如本研究證據(jù)推薦的中性粒細胞減少癥和FN病人常見的潛在感染部位的評估和檢查、手衛(wèi)生以及體溫監(jiān)測等建議均為A級推薦。但目前,針對中性粒細胞減少癥相關(guān)感染預防與控制措施仍存在爭議,其在不同國家及其醫(yī)院應用具有高度異質(zhì)性[32]。如在飲食衛(wèi)生方面,以往研究推薦中性粒細胞減少性飲食或無菌飲食,但經(jīng)研究證實,中性粒細胞減少性飲食或無菌飲食與無限制性飲食相比,病人感染率和死亡率無差別[33]。因此,本證據(jù)總結(jié)推薦中性粒細胞減少癥病人無特殊飲食限制,臨床可根據(jù)病人情況進行個性化飲食管理。目前,我國尚未制定中性粒細胞減少癥感染與預防方面的相關(guān)制度與措施,為此,可以開展相關(guān)研究,依據(jù)本證據(jù)整合結(jié)果,各醫(yī)療機構(gòu)根據(jù)臨床情境制定中性粒細胞減少癥病人相關(guān)感染防控方案。
3.3 實施健康教育,提升腫瘤病人居家自我管理水平
證據(jù)26~33匯總了健康教育的時機、形式和內(nèi)容。證據(jù)推薦在病人化療前即對病人進行中性粒細胞減少癥相關(guān)健康教育[23],為病人提供包括書面、口頭或基于網(wǎng)絡的多形式的健康教育,以提高病人自我管理能力。但本研究納入的指南或共識推薦的健康宣教內(nèi)容不夠全面和系統(tǒng),盡管NCCN[16?17]和ASCO等組織已經(jīng)開發(fā)了病人教育材料,但其并不都是基于證據(jù)的,仍有待開展研究進一步完善。由于病人出院前可能預防性接受了粒細胞集落刺激因子治療,以降低中性粒細胞減少癥及相關(guān)并發(fā)癥的發(fā)生率,導致病人發(fā)生中性粒細胞減少癥、FN或感染的風險更可能出現(xiàn)在居家后或者化療間歇期。因此,證據(jù)推薦醫(yī)護人員需要告知病人在此期間定時監(jiān)測體溫、復查血常規(guī)、保持環(huán)境和個人衛(wèi)生等注意事項,以提高病人對自身健康狀況的依從性和警覺性。護士在健康教育方面發(fā)揮關(guān)鍵作用[34],但相關(guān)研究顯示,護士中性粒細胞減少癥相關(guān)知識水平明顯不足[31,35],不能充分發(fā)揮其健康教育角色,需要加強培訓,為病人提供正確的健康指導。
3.4 開展隨訪和監(jiān)測,提高FN風險管理效率
證據(jù)34~37匯總了開展隨訪與居家監(jiān)測的人員、形式和具體內(nèi)容。建議由受過培訓的醫(yī)生、護士、醫(yī)生助理進行隨訪,并應具有管理發(fā)熱和中性粒細胞減少癥病人的經(jīng)驗和專業(yè)知識[16],以規(guī)范預防和管理腫瘤病人中性粒細胞減少癥和FN。對具有潛在FN風險的病人應制定隨訪或監(jiān)測計劃,及時開展基于手機應用程序、網(wǎng)絡或電話形式的遠程隨訪或監(jiān)測。目前的中性粒細胞減少癥監(jiān)測方案依賴于臨床血常規(guī)結(jié)果,僅限于擁有實驗室基礎設施的醫(yī)院或社區(qū)。因此,未來可引入新型非侵入性技術(shù),允許病人在家中進行自動化和頻繁的中性粒細胞減少監(jiān)測[36]。
4 小結(jié)
本研究共匯總4個方面、37條關(guān)于腫瘤病人FN非藥物預防及管理的最佳證據(jù),包括風險評估、感染預防與控制、健康教育、隨訪與監(jiān)測,為規(guī)范腫瘤病人FN非藥物預防及管理提供科學和可操作性的循證建議,有助于相關(guān)臨床護理實踐的開展。由于本研究納入文獻大多來源于國外,病人特征和醫(yī)療服務存在地域及文化差異,建議臨床醫(yī)護人員在應用證據(jù)時應全面評估臨床情境,分析證據(jù)的促進及阻礙因素,審慎合理地將證據(jù)運用于臨床。
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(收稿日期:2024-08-04;修回日期:2025-02-10)
(本文編輯"張建華)