Sepsis - Sepsis

Uchish uchun qarang Sepsis (chivin).

Sepsis
Boshqa ismlarSepticemiya, qon bilan zaharlanish
Bloodculturetubes.JPG
Qon madaniyati butilkalar: to'q sariq qopqoq anaeroblar, yashil shapka aeroblar, va bolalardan qon namunalari uchun sariq qopqoq[1]
Talaffuz
MutaxassisligiYuqumli kasallik
AlomatlarIsitma, yurak tezligini oshirish, past qon bosimi, nafas olish tezligini oshirdi, chalkashlik[2]
SabablariImmunitetga qarshi javob infektsiya tomonidan qo'zg'atilgan[3][4]
Xavf omillariYosh yoki qarilik, saraton, diabet, katta travma, kuyish[2]
Diagnostika usuliTizimli yallig'lanish reaktsiyasi sindromi (SIRS),[3] qSOFA[5]
DavolashVena ichiga yuboriladigan suyuqliklar, mikroblarga qarshi vositalar[2][6]
Prognoz10 dan 80% gacha o'lim xavfi[5][7]
ChastotaniYiliga 1000 ga 0,2-3 (rivojlangan dunyo)[7][8]

Sepsis organizmning reaktsiyasi paytida paydo bo'ladigan hayot uchun xavfli holat infektsiya o'z to'qimalariga va organlariga shikast etkazadi.[5] Ushbu boshlang'ich bosqichdan keyin immunitet tizimi.[9] Umumiy belgilar va alomatlar kiradi isitma, yurak tezligini oshirish, nafas olish tezligini oshirdi va chalkashlik.[2] Yo'tal kabi o'ziga xos infektsiya bilan bog'liq alomatlar ham bo'lishi mumkin zotiljam, yoki og'riqli siyish bilan buyrak infektsiyasi.[3] Juda yosh, qari va a bilan odamlar immunitetning zaiflashishi ma'lum bir infektsiyaning alomatlari bo'lmasligi mumkin va tana harorati past bo'lishi mumkin yoki o'rniga oddiy isitma.[3] Kuchli sepsis sabablari organning yomon ishlashi yoki qon oqimi.[10] Mavjudligi past qon bosimi, yuqori qon laktat, yoki siydik miqdori pastligi yomon qon oqishini taklif qilishi mumkin.[10] Septik shok sepsis tufayli past qon bosimi bo'lib, keyinchalik yaxshilanmaydi suyuqlikni almashtirish.[10]

Sepsis an yallig'lanish immuniteti infektsiya tomonidan qo'zg'atilgan.[3][4] Bakterial infektsiyalar eng keng tarqalgan sababdir, ammo qo'ziqorin, virusli va protozoan infektsiyalar sepsisga ham olib kelishi mumkin.[3] Birlamchi infektsiyaning umumiy joylariga o'pka, miya, siydik yo'llari, teri va qorin bo'shlig'i organlari.[3] Xavf omillari orasida juda yosh, keksa yosh, immunitet tizimining zaiflashishi kabi holatlar mavjud saraton yoki diabet, katta travma, yoki kuyish.[2] Ilgari sepsis tashxisi kamida ikkitasining mavjudligini talab qilar edi tizimli yallig'lanish reaktsiyasi sindromi (SIRS) taxmin qilingan infektsiyani belgilash mezonlari.[3] 2016 yilda qisqartirilgan ketma-ket organ etishmovchiligini baholash ballari Deb nomlanuvchi (SOFA ballari) tez SOFA bal (qSOFA), SIRS diagnostika tizimini almashtirdi.[5] Sepsis uchun qSOFA mezonlari quyidagi uchtadan kamida ikkitasini o'z ichiga oladi: nafas olish tezligining oshishi, ong darajasining o'zgarishi va past qon bosimi.[5] Sepsis bo'yicha ko'rsatmalar olishni tavsiya qiladi qon madaniyati antibiotiklarni boshlashdan oldin; ammo, tashxis talab qilmaydi yuqtirgan qon.[3] Tibbiy tasvir infektsiyaning mumkin bo'lgan joyini qidirishda foydalidir.[10] Shunga o'xshash belgilar va alomatlarning boshqa potentsial sabablari kiradi anafilaksi, buyrak usti etishmovchiligi, qon miqdori past, yurak etishmovchiligi va o'pka emboliya.[3]

Sepsis zudlik bilan davolanishni talab qiladi vena ichiga yuboriladigan suyuqliklar va mikroblarga qarshi vositalar.[2][6] Davomiy parvarish ko'pincha an intensiv terapiya bo'limi.[2] Agar etarli sinov bo'lsa suyuqlikni almashtirish qon bosimini ushlab turish uchun etarli emas, keyin dori vositalaridan foydalanish qon bosimini ko'tarish zarur bo'lib qoladi.[2] Mexanik shamollatish va diyaliz navbati bilan o'pka va buyrak faoliyatini qo'llab-quvvatlash uchun kerak bo'lishi mumkin.[2] A markaziy venoz kateter va an arterial kateter qon oqimiga kirish va davolanishni boshqarish uchun joylashtirilishi mumkin.[10] Boshqa foydali o'lchovlarga quyidagilar kiradi yurak chiqishi va yuqori vena kava kislorod bilan to'yinganligi.[10] Sepsisli odamlar profilaktika choralariga muhtoj chuqur tomir trombozi, stress yarasi va bosim yarasi agar boshqa shartlar bunday aralashuvga to'sqinlik qilmasa.[10] Ba'zi odamlar qattiq nazoratdan foyda ko'rishlari mumkin qon shakar darajalari insulin.[10] Dan foydalanish kortikosteroidlar munozarali bo'lib, ba'zi sharhlar foyda keltiradi,[11][12] va boshqalar yo'q.[13]

Kasallikning og'irligi qisman natijani belgilaydi.[7] Sepsisdan o'lish xavfi 30% ni tashkil qiladi, og'ir sepsis uchun esa 50% gacha, septik shok esa 80% ni tashkil qiladi.[7] Sepsis 2017 yilda taxminan 49 million kishiga ta'sir qildi, 11 million o'lim (dunyo bo'ylab har 5 o'limdan 1).[14] In rivojlangan dunyo, har 1000 kishi boshiga 0,2 dan 3 kishiga sepsis ta'sir qiladi, natijada Qo'shma Shtatlarda yiliga millionga yaqin holat yuzaga keladi.[7][8] Kasallik darajasi oshib bormoqda.[10] Sepsis erkaklar orasida ayollarga qaraganda ko'proq uchraydi.[3] Sepsisning ta'riflari o'sha davrga to'g'ri keladi Gippokrat.[15] "Septikemiya" va "qon bilan zaharlanish" atamalari turli xil qo'llanilgan va endi tavsiya etilmaydi.[15][16]

Video xulosasi (skript)

Belgilari va alomatlari

Haqiqiy sabab bilan bog'liq alomatlardan tashqari, sepsis bilan og'rigan odamlarda a bo'lishi mumkin isitma, tana harorati past, tez nafas olish, tez yurak urishi, chalkashlik va shish.[17] Dastlabki belgilarga tez yurak urishi kiradi, siydik chiqarishning pasayishi va yuqori qon shakar. O'rnatilgan sepsis belgilariga chalkashliklar kiradi, metabolik atsidoz (bu tezroq nafas olish tezligiga olib kelishi mumkin) nafas olish alkalozi ), past qon bosimi kamayganligi sababli tizimli qon tomirlariga qarshilik, yuqori yurak chiqishi va qon ivishidagi buzilishlar bu organ etishmovchiligiga olib kelishi mumkin.[18] Isitma sepsisda eng ko'p uchraydigan alomatdir, ammo ba'zi odamlar, masalan, qariyalar yoki immunitet tanqisligi bo'lgan odamlarda isitma bo'lmasligi mumkin.[19]

The qon bosimining pasayishi sepsisda kuzatilishi mumkin engillik va uchun mezonlarning bir qismidir septik shok.[20]

Sababi

Odatda sepsisga olib keladigan infektsiyalar bakterial lekin bo'lishi mumkin qo'ziqorin yoki virusli.[21] Gram-musbat bakteriyalar 1950-yillarda antibiotiklar kiritilishidan oldin sepsisning asosiy sababi bo'lgan. Antibiotiklarni kiritgandan so'ng, grammusbat bakteriyalar 1960 yildan 1980 yillarga qadar sepsisning asosiy sababiga aylandi.[22] 1980-yillardan keyin, grammusbat bakteriyalar, eng keng tarqalgan stafilokokklar, sepsis holatlarining 50% dan ortig'ini keltirib chiqaradi deb o'ylashadi.[8][23] Boshqa keng tarqalgan bakteriyalar kiradi Streptokokk pyogenlari, Escherichia coli, Pseudomonas aeruginosa va Klebsiella turlari.[24] Qo'ziqorin sepsis og'ir sepsis va septik shok holatlarining taxminan 5% ni tashkil qiladi; qo'ziqorin sepsisining eng keng tarqalgan sababi bu infektsiya Candida turlari xamirturush,[25] tez-tez kasalxonada yuqtirilgan infektsiya.

Kuchli sepsisga olib keladigan infektsiyaning eng ko'p uchraydigan joylari o'pka, qorin va siydik yo'llari.[21] Odatda, sepsis holatlarining 50% o'pkada infektsiya bo'lib boshlanadi. Uchdan bir yarim hollarda infektsiyaning manbai aniq emas.[21]

Tashxis

Sepsisni to'g'ri boshqarish uchun erta tashxis qo'yish kerak, chunki tez terapiyani boshlash og'ir sepsisdan o'limni kamaytirishning kalitidir.[10] Ba'zi shifoxonalar tomonidan ishlab chiqarilgan ogohlantirishlardan foydalaniladi elektron tibbiy yozuvlar mumkin bo'lgan holatlarga imkon qadar erta e'tibor qaratish.[26]

Sepsisga shubha qilingan dastlabki uch soat ichida diagnostik tadqiqotlar o'tkazilishi kerak oq qon hujayralari soni, antibiotiklarni boshlashdan oldin sarum laktatni o'lchash va tegishli madaniyatlarni olish, agar bu ularni ishlatishni 45 daqiqadan ko'proq kechiktirmasa.[10] Ta'sir etuvchi organizm (lar) ni aniqlash uchun kamida ikkita to'plam qon madaniyati bilan shishalarni ishlatish ommaviy axborot vositalari uchun aerob va anaerob organizmlar zarur. Hech bo'lmaganda bittasini chizish kerak teri orqali va 48 soatdan ko'proq vaqt davomida mavjud bo'lgan har bir tomirga kirish moslamasi (masalan, IV kateter) orqali.[10] Bakteriyalar mavjud qonda mavjud faqat taxminan 30% hollarda.[27] Yana bir aniqlanishi mumkin bo'lgan usul polimeraza zanjiri reaktsiyasi. Agar infektsiyaning boshqa manbalariga shubha tug'ilsa, antibiotiklardan foydalanishni kechiktirmasa, siydik, miya omurilik suyuqligi, yaralar yoki nafas olish yo'llari sekretsiyasi kabi bu manbalarning madaniyatini olish kerak.[10]

Olti soat ichida, agar 30 ml / kg gacha bo'lgan dastlabki reanimatsiyaga qaramay, qon bosimi past bo'lsa yoki boshlang'ich laktat ≥ to'rt mmol / l (36 mg / dl) bo'lsa, markaziy venoz bosim va markaziy venoz kislorod bilan to'yinganligi o'lchash kerak.[10] Agar boshlang'ich laktat ko'tarilgan bo'lsa, laktatni qayta o'lchash kerak.[10] Dalillar parvarishlash nuqtasi laktat o'lchovi odatdagi o'lchov usullari bo'yicha, ammo yomon.[28]

O'n ikki soat ichida favqulodda manbalarni nazorat qilishni talab qiladigan har qanday infektsiya manbasini tashxislash yoki chiqarib tashlash juda muhimdir, masalan, yumshoq to'qimalarning nekrotizan infektsiyasi, infektsiyani keltirib chiqaradi. qorin bo'shlig'i qoplamasining yallig'lanishi, an o't yo'lining infektsiyasi yoki ichak infarkti.[10] Nayzalangan ichki organ (qorin bo'shlig'i rentgenogrammasi yoki tomografiya paytida bo'sh havo), g'ayritabiiy ko'krak qafasi rentgenogrammasi bilan izchil zotiljam (fokal opakifikatsiya bilan) yoki petexiya, purpura, yoki purpura fulminans infektsiyaning mavjudligini ko'rsatishi mumkin.

Ta'riflar

Tizimli yallig'lanish reaktsiyasi sindromi[29]
TopishQiymat
Harorat<36 ° C (96,8 ° F) yoki> 38 ° C (100,4 ° F)
Yurak urish tezligi> 90 / min
Nafas olish darajasi> 20 / min yoki PaCO2<32 mm simob ustuni (4,3 kPa)
WBC<4x109/ L (<4000 / mm³),> 12x109/ L (> 12,000 / mm³), yoki -10% guruhlar
Sepsis bosqichlari. Sepsis bosqichlarining rivojlanishini o'rgatish uchun o'quv vositasi

Ilgari sepsisni aniqlash uchun SIRS mezonlari ishlatilgan. Agar SIRS mezonlari salbiy bo'lsa, odamda sepsis bo'lishi ehtimoldan yiroq emas; agar u ijobiy bo'lsa, odamda sepsis borligi ehtimoli o'rtacha. SIRS ma'lumotlariga ko'ra sepsisning turli darajalari bo'lgan: sepsis, og'ir sepsis va septik shok.[16] SIRS ta'rifi quyida keltirilgan:

2016 yilda skrining o'rnini bosuvchi yangi konsensusga erishildi tizimli yallig'lanish reaktsiyasi sindromi (SIRS) ketma-ket organ etishmovchiligini baholash bilan (SOFA ballari ) va qisqartirilgan versiyasi (qSOFA ).[5] QSOFA balining uchta mezoniga nafas olish tezligi daqiqada 22 nafasdan katta yoki teng, sistolik qon bosimi 100 mm simob ustuni yoki undan kam va o'zgargan ruhiy holat kiradi.[5] QSOFA mezonlaridan 2 tasi bajarilganda sepsis gumon qilinadi.[5] SOFA ballari reanimatsiya bo'limida (ICU) ishlatilishi kerak edi, u erda u davolanishga yotqizilganidan keyin qo'llaniladi va keyin har 48 soatda takrorlanadi, qSOFA esa ICU tashqarisida ishlatilishi mumkin edi.[19] QSOFA balining ba'zi bir afzalliklari shundaki, u tezda boshqarilishi mumkin va laboratoriyalarni talab qilmaydi.[19] Biroq, Amerika ko'krak shifokorlari kolleji (CHEST) qSOFA va SOFA mezonlari jiddiy infektsiyani tashxisini kechikishiga olib kelishi va davolanishni kechiktirishga olib kelishi mumkinligi haqida xavotir bildirdi.[31] SIRS mezonlari juda sezgir bo'lishi va sepsisni aniqlashda etarlicha aniq bo'lmasligi mumkin bo'lsa-da, SOFA ham cheklovlarga ega va SIRS ta'rifini almashtirish uchun mo'ljallanmagan.[32] qSOFA, shuningdek, SIRS bilan o'lim xavfiga mos keladigan darajada sezgir, ammo skrining uchun yaxshiroq bo'lishi aniqlandi.[33]

Oxirgi organlarning disfunktsiyasi

Asosiy maqola: Ko'p organ disfunktsiyasi sindromi

Misollari so'nggi organlarning disfunktsiyasi quyidagilarni o'z ichiga oladi:[34]

Pediatriyada SIRS uchun end-organ disfunktsiyasining aniqroq ta'riflari mavjud.[35]

Ammo konsensus ta'riflari rivojlanishda davom etmoqda, to'shakda yotadigan klinik tajribani aks ettirish uchun sepsis belgilari va alomatlari ro'yxati so'nggi paytlarda kengaymoqda.[17]

Biomarkerlar

2013 yil ko'rib chiqish dan foydalanishni qo'llab-quvvatlovchi o'rtacha sifatli dalillar mavjud prokalsitonin sepsisni SIRS yuqumli bo'lmagan sabablaridan ajratish usuli sifatida daraja.[27] Xuddi shu sharhda topilgan sezgirlik testning 77%, o'ziga xosligi esa 79%. Mualliflar prokalsitonin sepsis uchun foydali diagnostika markeri bo'lib xizmat qilishi mumkin deb taxmin qilishgan, ammo uning darajasi tashxisni aniq belgilamasligi haqida ogohlantirishgan.[27] 2012 yilgi muntazam tekshiruv shuni aniqladi eruvchan urokinaza tipidagi plazminogen faollashtiruvchi retseptorlari (SuPAR) yallig'lanishning o'ziga xos bo'lmagan belgisidir va sepsisga aniq tashxis qo'ymaydi.[36] Shu bilan taqqoslaganda, SuPARning prognostik qiymati bor, degan xulosaga kelishdi, chunki yuqori SuPAR darajasi sepsis bilan kasallanganlarda o'lim darajasi oshishi bilan bog'liq.[36] Laktat miqdorini ketma-ket o'lchash (taxminan har 4 soatda 6 soatda) davolashga rahbarlik qilishi mumkin va sepsisdagi o'lim darajasi pastligi bilan bog'liq.[19]

Differentsial diagnostika

The differentsial diagnostika sepsis uchun keng va SIRSning tizimli belgilarini keltirib chiqarishi mumkin bo'lgan yuqumsiz holatlarni tekshirishi (istisno qilishi) kerak: spirtli ichimliklarni olib tashlash, o'tkir pankreatit, kuyish, o'pka emboliya, tirotoksikoz, anafilaksi, buyrak usti etishmovchiligi va neyrogen shok.[18][37] Kabi giperinflamatuar sindromlar gemofagotsitik limfohistiotsitoz (HLH) o'xshash belgilarga ega bo'lishi mumkin va differentsial diagnostikada.[38]

Yangi tug'ilgan sepsis

Umumiy klinik foydalanishda, yangi tug'ilgan sepsis bakterialni anglatadi qon oqimi infektsiyasi kabi hayotning birinchi oyida meningit, zotiljam, pielonefrit, yoki gastroenterit,[39] ammo neonatal sepsis qo'ziqorinlar, viruslar yoki parazitlar bilan yuqishi tufayli ham bo'lishi mumkin.[39] Gemodinamik murosaga yoki nafas etishmovchiligiga oid mezon foydali emas, chunki ular aralashish uchun juda kech.

Patofiziologiya

Sepsis, ma'lum bir yuqumli patogen (lar) ga va mezbon immunitet tizimining holatiga bog'liq bo'lgan omillar kombinatsiyasidan kelib chiqadi.[40] Haddan tashqari yallig'lanish bilan ajralib turadigan sepsisning dastlabki bosqichi (ba'zida a sitokin bo'roni ) dan keyin uzoq muddat davom etishi mumkin immunitet tizimining pasayishi.[41][9] Ushbu bosqichlarning har biri o'limga olib kelishi mumkin. Boshqa tomondan, tizimli yallig'lanish reaktsiyasi sindromi (SIRS) infektsiyasi bo'lmagan odamlarda, masalan, kuyish, politeravma yoki dastlabki holat pankreatit va kimyoviy pnevmonit. Shu bilan birga, sepsis ham SIRSga o'xshash javobni keltirib chiqaradi.[16]

Mikrobial omillar

Bakterial virulentlik omillari, kabi glikokaliks va turli xil yopishqoq moddalar, kolonizatsiyaga, immunitetdan qochishga va xostda kasallik paydo bo'lishiga yo'l qo'ying.[40] Sepsis sabab bo'lgan grammusbat bakteriyalar asosan mezbonning javobiga bog'liq deb o'ylashadi lipid A ning tarkibiy qismi lipopolisakkarid deb nomlangan endotoksin.[42][43] Sepsis sabab bo'lgan grammusbat bakteriyalar hujayra devoriga immunologik ta'siridan kelib chiqishi mumkin lipotexoik kislota.[44] Bakterial ekzotoksinlar kabi harakat qiladi superantigenlar sepsisga olib kelishi mumkin.[40] Superantigenlar bir vaqtning o'zida bog'lanadi asosiy gistosayish kompleksi va T-hujayrali retseptorlari yo'qligida antigen taqdimoti. Ushbu majburiy retseptorlarning o'zaro ta'siri yallig'lanishga qarshi kimyoviy signallarni ishlab chiqarishni keltirib chiqaradi (sitokinlar ) T-hujayralar tomonidan.[40]

Oddiy septikka olib kelishi mumkin bo'lgan bir qator mikrobial omillar mavjud yallig'lanish kaskadi. Invazion patogen uning tomonidan tan olinadi patogen bilan bog'liq bo'lgan molekulyar naqshlar (PAMP). PAMP-larga lipopolisaxaridlar va flagellin grammusbat bakteriyalarda, muramil dipeptid ichida peptidoglikan gram-musbat bakterial hujayra devorining va CpG bakterial DNK. Ushbu PAMP lar tomonidan tan olingan naqshni aniqlash retseptorlari Tug'ma immunitet tizimining (PRR), ular membrana bilan bog'langan yoki sitosolik bo'lishi mumkin.[45] PRRlarning to'rtta oilasi mavjud: pullik retseptorlari, C tipidagi lektin retseptorlari NODga o'xshash retseptorlar, va RIG-Iga o'xshash retseptorlari. Har doim PAMP va PRR assotsiatsiyasi bir qator hujayralararo signalizatsiya kaskadlarini keltirib chiqaradi. Binobarin, kabi transkripsiya omillari yadro omil-kappa B va faollashtiruvchi protein-1, yallig'lanishga qarshi va yallig'lanishga qarshi sitokinlarning ekspressionini tartibga soladi.[46]

Xost omillari

Mikroblarni aniqlashda antijenler, mezbon tizimli immunitet tizimi faollashadi. Immunitet hujayralari nafaqat patogen bilan bog'liq bo'lgan molekulyar naqshlarni taniydi, balki zarar bilan bog'liq molekulyar naqshlar shikastlangan to'qimalardan. Keyin nazoratsiz immunitet faollashadi, chunki leykotsitlar infektsiyaning aniq joyiga jalb qilinmaydi, aksincha ular butun tanada to'planadi. Keyin, an immunosupressiya proinflamatuar holat paydo bo'ladi T yordamchi hujayra 1 (TH1) TH2 ga o'tkaziladi,[47] vositachilik qiladi interleykin 10, bu "kompensator yallig'lanishga qarshi javob sindromi" deb nomlanadi.[22] The apoptoz (hujayralar o'limi) limfotsitlar immunosupressiyani yanada yomonlashtiradi. Neytrofillar, monotsitlar, makrofaglar, dendritik hujayralar, CD4 + T hujayralari va B hujayralari barchasi apoptozga uchraydi, aksincha tartibga soluvchi T hujayralari ko'proq apoptozga chidamli.[9] Keyinchalik, ko'p organ etishmovchiligi paydo bo'ladi, chunki to'qimalar inhibisyoni tufayli kisloroddan samarali foydalana olmaydi sitoxrom s oksidaza.[47]

Yallig'lanish ta'siriga sabab bo'ladi ko'p organlarning buzilishi sindromi quyida tavsiflangan turli xil mexanizmlar orqali. O'pka tomirlarining o'tkazuvchanligini oshirish alveolalarga suyuqlik oqishini keltirib chiqaradi, natijada o'pka shishi va o'tkir nafas yetishmasligi sindromi (ARDS). Jigarda kisloroddan foydalanishning buzilishi buziladi safro tuzi transport, sabab sariqlik (terining sarg'ish rangsizlanishi). Buyraklarda kislorod etishmovchiligida naycha epiteliya hujayrasi shikastlanadi (buyrak tubulalari bilan o'ralgan hujayralar) va shu sababli buyrakning o'tkir shikastlanishi (AKI). Ayni paytda, yurakda kaltsiyni tashish va ishlab chiqarishning pastligi adenozin trifosfat (ATP), miyokardiy tushkunlikni keltirib chiqarishi, yurak kontraktiliyasini pasaytirishi va sabab bo'lishi mumkin yurak etishmovchiligi. In oshqozon-ichak trakti, shilliq qavatning o'tkazuvchanligini oshirish mikroflorani o'zgartiradi, shilliq qavat qon ketishini keltirib chiqaradi paralitik ichak. In markaziy asab tizimi, miya hujayralarining bevosita shikastlanishi va neyrotranslyasiyalarning buzilishi o'zgargan ruhiy holatni keltirib chiqaradi.[48] Kabi sitokinlar o'simta nekrozi omil, interleykin 1 va interleykin 6 faollashtirishi mumkin prokoagulyatsiya omillar qon tomirlarini qoplaydigan hujayralar, endoteliy zararlanishiga olib keladi. Buzilgan endotelial sirt antikoagulyant xususiyatlarini inhibe qiladi, shuningdek ko'payadi antifibrinoliz, bu tomir ichidagi pıhtılaşmaya olib kelishi mumkin qon pıhtıları kichik qon tomirlarida va ko'p organ etishmovchiligi.[49]

Sepsis bilan og'rigan bemorlarda qon bosimining pastligi har xil jarayonlarning natijasidir, shu jumladan kimyoviy moddalarning ortiqcha ishlab chiqarilishi qon tomirlarini kengaytiradi kabi azot oksidi, kimyoviy moddalar etishmasligi qon tomirlarini toraytiradi kabi vazopressin va faollashtirish ATP sezgir kaliy kanallari.[50] Jiddiy sepsis va septik shok bilan kasallanganlarda ushbu hodisalar ketma-ketligi bir turga olib keladi qon aylanish shoki sifatida tanilgan tarqatuvchi zarba.[51]

Menejment

Vena ichiga yuboriladigan suyuqliklar

Erta tan olinishi va yo'naltirilgan boshqarish sepsis natijalarini yaxshilashi mumkin. Amaldagi professional tavsiyalar tashxis qo'yilgandan so'ng imkon qadar tezroq bajarilishi kerak bo'lgan bir qator harakatlarni ("to'plamlar") o'z ichiga oladi. Dastlabki uch soat ichida sepsisga chalingan odam qon bosimi pastligi yoki boshqa organlarga qon bilan etarli darajada ta'minlanmaganligi to'g'risida boshqa dalillar mavjud bo'lsa (laktat darajasining ko'tarilishi bilan tasdiqlangan bo'lsa) antibiotiklar va vena ichiga suyuqlik qabul qilishi kerak edi; Ushbu davrda qon madaniyatini olish kerak. Olti soatdan keyin qon bosimi etarli bo'lishi kerak, qon bosimi va organlarning qon bilan ta'minlanishini diqqat bilan kuzatib borish kerak va agar u ko'tarilgan bo'lsa, laktat yana o'lchov qilinadi.[10] Tegishli to'plam, "Sepsis olti ", keng tarqalgan bo'lib ishlatilmoqda Birlashgan Qirollik; buning uchun bir soat ichida antibiotiklarni qabul qilish, qon madaniyati, laktat va gemoglobinni aniqlash, siydik chiqarishni nazorat qilish, yuqori oqimli kislorod va tomir ichiga yuborish kerak.[52][53]

Suyuqlikni o'z vaqtida yuborishdan tashqari va antibiotiklar, sepsisni boshqarish, shuningdek, yuqtirilgan suyuqlik kollektsiyalarini jarrohlik yo'li bilan drenajlashni va organlarning disfunktsiyasini tegishli qo'llab-quvvatlashni o'z ichiga oladi. Bunga o'z ichiga olishi mumkin gemodializ yilda buyrak etishmovchiligi, mexanik shamollatish yilda o'pka disfunktsiya, qon quyish qon mahsulotlari va qon aylanishining buzilishi uchun dori va suyuqlik terapiyasi. Etarli ovqatlanishni ta'minlash - afzalroq enteral ovqatlanish, lekin agar kerak bo'lsa, tomonidan parenteral ovqatlanish - uzoq davom etgan kasallik paytida muhimdir.[10] Oldini olish uchun dori chuqur tomir trombozi va oshqozon yarasi ham ishlatilishi mumkin.[10]

Antibiotiklar

Antibiotiklarni boshlashni kechiktirmasdan qon to'plamlarining ikki to'plami (aerobik va anaerobik) tavsiya etiladi. Nafas olish sekretsiyasi, siydik, yaralar, miya omurilik suyuqligi va kateterni kiritish joylari (boshqa joyda 48 soatdan ortiq) kabi boshqa joylardan ekish tavsiya etiladi, agar bu joylardan yuqtirishga shubha bo'lsa.[6] Kuchli sepsis va septik shokda, keng spektrli antibiotiklar (odatda ikkita, a b-laktam antibiotik keng qamrovli yoki keng spektrli karbapenem ftorxinolonlar, makrolidlar yoki aminoglikozidlar bilan birlashtirilgan) tavsiya etiladi. Antibiotiklarni tanlash inson hayotini aniqlashda muhim ahamiyatga ega.[51][6] Ba'zilar antibiotiklarni qabul qilishning kechiktirilgan har bir soati uchun o'lim bilan bog'liq 6% o'sish borligini aytib, ularga tashxis qo'yilgandan keyin bir soat ichida berishni tavsiya qiladilar.[30][51] Boshqalar erta administratsiyadan foyda ko'rmadilar.[54]

Dastlabki antibiotiklar sxemasi uchun eng maqbul tanlovni bir necha omillar belgilaydi. Ushbu omillar orasida infektsiya a deb hisoblanadigan antibiotiklarga bakterial sezgirlikning mahalliy namunalari kiradi kasalxona yoki jamoat tomonidan yuqtirilgan infektsiya va qaysi organ tizimlari yuqtirilgan deb hisoblanadi.[51][19] Antibiotiklar sxemasi har kuni qayta ko'rib chiqilishi va agar kerak bo'lsa toraytirilishi kerak. Davolashning davomiyligi odatda 7-10 kun bo'lib, kulturalar natijalari bo'yicha qo'llaniladigan antibiotik turi bilan qo'llaniladi. Agar madaniy natija salbiy bo'lsa, antibiotiklar odamning klinik javobiga qarab kamaytirilishi yoki agar yuqtirish ehtimoli kamayishi uchun infektsiya bo'lmasa, umuman to'xtatilishi kerak. bir nechta dorilarga qarshilik organizmlar. Odamlar yuqtirish xavfi yuqori bo'lsa bir nechta dorilarga qarshilik kabi organizmlar Pseudomonas aeruginosa, Acinetobacter baumannii, grammusbat organizmga xos bo'lgan antibiotik qo'shilishi tavsiya etiladi. Uchun Metitsillinga chidamli aureus Staphylococcus (MRSA), vankomitsin yoki teikoplanin tavsiya etiladi. Uchun Legionella infektsiya, qo'shilish makrolid yoki ftorxinolon tanlangan. Agar qo'ziqorin infektsiyasiga shubha bo'lsa, an echinokandin, kabi kaspofungin yoki mikafungin, og'ir sepsisli odamlar uchun tanlanadi, keyin triazol (flukonazol va itrakonazol ) kamroq kasal bo'lgan odamlar uchun.[6] SIRS kabi yuqumli kelib chiqishi bo'lmagan odamlarda antibiotiklarni uzoq muddat profilaktika qilish tavsiya etilmaydi o'tkir pankreatit va kuyish sepsisga shubha qilinmasa.[6]

Kuniga bir marta dozalash aminoglikozid buyrak zaharlanishisiz klinik javob uchun plazmadagi eng yuqori konsentratsiyaga erishish uchun etarli. Shu bilan birga, kam miqdordagi taqsimlangan antibiotiklar uchun (vankomitsin, teikoplanin, kolistin) infektsiyalarga qarshi kurashish uchun etarli terapevtik darajaga erishish uchun yuklash dozasi talab qilinadi. Beta-laktam antibiotiklarining tez-tez infuziyalari umumiy sutkalik dozadan oshmasdan antibiotiklarni yuqori darajada ushlab turishga yordam beradi. minimal inhibitor kontsentratsiyasi (MIC), shuning uchun klinik javobni yaxshiroq ta'minlash.[6] Beta-laktam antibiotiklarini doimiy ravishda berish ularni vaqti-vaqti bilan berishdan ko'ra yaxshiroq bo'lishi mumkin.[55] Kirish terapevtik dori nazorati dori-darmonlarni etarli darajada terapevtik darajasini ta'minlash va shu bilan birga preparatni toksik darajaga ko'tarilishining oldini olish muhimdir.[6]

Vena ichiga yuboriladigan suyuqliklar

The Omon qolish Sepsis kampaniyasi birinchi uch soat ichida kattalarga 30 ml / kg suyuqlik berishni tavsiya qildi, so'ngra qon bosimi, siydik chiqarishi, nafas olish tezligi va kislorod bilan to'yinganligi bo'yicha suyuqlik titratsiyasi. o'rtacha arterial bosim (Xarita) 65 mm simob ustuni.[6] Bolalarda boshlang'ich miqdori 20 ml / kg shok holatida oqilona bo'ladi.[56] Qattiq sepsis va septik shok holatlarida bu erda a markaziy venoz kateter qon bosimini dinamik ravishda o'lchash uchun ishlatiladi, suyuqliklar qadar qo'llanilishi kerak markaziy venoz bosim 8-12 mm simob ustuniga etadi.[50] Ushbu maqsadlar amalga oshirilgach, markaziy venoz kislorod bilan to'yinganligi (ScvO2), ya'ni vena kavasida o'lchangan yurakka qaytganda venoz qonning kislorod bilan to'yinganligi optimallashtiriladi.[6] Agar ScvO2 70% dan kam bo'lsa, gemoglobin 10 g / dL ga yetishi uchun qon berilishi mumkin va keyin inotroplar ScvO2 optimallashtirilgunga qadar qo'shiladi.[40] Ularda o'tkir nafas yetishmasligi sindromi (ARDS) va etarli miqdordagi to'qima qon suyuqligi, ko'proq suyuqlik ehtiyotkorlik bilan berilishi kerak.[10]

Kristalloid eritmasi reanimatsiya uchun tanlangan suyuqlik sifatida tavsiya etiladi.[6] Albumin reanimatsiya uchun katta miqdordagi kristalloid kerak bo'lsa ishlatilishi mumkin.[6] Kristalloid eritmalari bilan unchalik katta farq yo'q gidroksietil kraxmal o'lim xavfi bo'yicha.[57] Kraxmallar xavfini oshiradi buyrakning o'tkir shikastlanishi,[57][58] va qon quyish zarurati.[59][60] Turli xil kolloid eritmalar (masalan, o'zgartirilgan jelatin) kristalloiddan hech qanday ustunlikka ega emas.[57] Albominning kristalloidlardan ham foydasi yo'q ko'rinadi.[61]

Qon mahsulotlari

Omon qolgan sepsis kampaniyasi tavsiya etilgan qadoqlangan qizil qon hujayralari qon quyish gemoglobin yo'q bo'lsa, 70 g / L dan past darajalar miokard ishemiyasi, gipoksemiya yoki o'tkir qon ketish.[6] 2014 yilda o'tkazilgan sinovda, maqsadli gemoglobinni 70 yoki 90 g / l dan yuqori darajada ushlab turish uchun qon quyish, hayot darajasi bilan farq qilmadi; shu bilan birga, quyish chegarasi past bo'lganlar, umuman olganda kamroq qon quyishgan.[62] Eritropoetin anemiyani septik shok bilan davolashda tavsiya etilmaydi, chunki u cho'kishi mumkin qon ivishi voqealar. Yangi muzlatilgan plazma qon quyish odatda rejalashtirilgan jarrohlik amaliyotidan oldin pıhtılaşma anomaliyalarini tuzatmaydi. Shu bilan birga, quyida trombotsitlar soni uchun trombotsitlarni quyish tavsiya etiladi (10 × 10)9/ L) qon ketish xavfi bo'lmagan holda yoki (20 × 10)9/ L) qon ketish xavfi yuqori yoki (50 × 10)9/ L) faol qon ketish bilan, rejalashtirilgan operatsiya yoki invaziv usuldan oldin.[6] IV immunoglobulin tavsiya etilmaydi, chunki uning foydali ta'siri noaniq.[6] Ning monoklonal va poliklonal preparatlari vena ichiga yuboriladigan immunoglobulin (IVIG) sepsis bilan kasallangan yangi tug'ilgan chaqaloqlarda va kattalarda o'lim darajasini pasaytirmang.[63] Dan foydalanish uchun dalillar IgM - IVIGning boyitilgan poliklonal preparatlari mos kelmaydi.[63] Boshqa tomondan, dan foydalanish antitrombin davolamoq tarqalgan tomir ichi qon ivishi ham foydali emas. Ayni paytda qonni tozalash texnikasi (masalan gemoperfuziya, yallig'lanish mediatorlari va bakterial toksinlarni qondan olib tashlash uchun plazma filtratsiyasi va birlashtirilgan plazma filtrlash adsorbsiyasi), shuningdek, septik shok uchun omon qolish foydasini ko'rsatmaydi.[6]

Vazopressorlar

Agar odam etarli darajada reanimatsiya qilingan bo'lsa, ammo o'rtacha arterial bosim 65 mm simob ustunidan katta emas, vazopressorlar tavsiya etiladi.[6] Norepinefrin (noradrenalin) dastlabki tanlov sifatida tavsiya etiladi.[6] Septik shok paytida vazopressor terapiyasini boshlashni kechiktirish o'limning ko'payishi bilan bog'liq.[64]

Norepinefrin ko'pincha gipotenziv septik shokni davolashning birinchi bosqichi sifatida qo'llaniladi, chunki dalillar vazopressinning nisbatan kamligi borligini, shok 24 soatdan 48 soatgacha davom etayotganligini ko'rsatadi.[65] Norepinefrin qon bosimini vazokonstriksion ta'sir orqali oshiradi, ozgina ta'sir qiladi qon tomir hajmi va yurak urishi.[6] Ba'zi odamlarda o'rtacha arterial bosimni oshirish uchun zarur bo'lgan vazopressorning zaruriy dozasi u toksik bo'lib qolishidan juda yuqori bo'lishi mumkin.[66] Vazopressorning kerakli dozasini kamaytirish uchun epinefrin qo'shilishi mumkin.[66] Epinefrin ko'pincha hipotenziv shokni davolashda birinchi qatorda qo'llanilmaydi, chunki u qorin bo'shlig'i a'zolariga qon quyilishini kamaytiradi va laktat miqdorini oshiradi.[65] Vazopressinni septik shokda ishlatish mumkin, chunki tadqiqotlar shuni ko'rsatadiki, zarba 24 soatdan 48 soatgacha davom etganda, vazopressinning nisbiy etishmovchiligi mavjud. Shu bilan birga, vazopressin yurak, barmoq / oyoq barmoqlari va qorin a'zolariga qon quyilishini pasaytiradi, natijada bu to'qimalarga kislorod etkazib berilmaydi.[6] Dopamin odatda tavsiya etilmaydi. Dopamin yurakning qon tomir hajmini oshirish uchun foydali bo'lsa-da, bu ko'proq narsani keltirib chiqaradi g'ayritabiiy yurak ritmlari noradrenalindan va shuningdek immunosupressiv ta'sirga ega. Dopamin buyrakda himoya xususiyatiga ega ekanligi isbotlanmagan.[6] Dobutamin yurak ishlab chiqarishni ko'paytirish va to'qimalarga qon oqimini to'g'irlash uchun gipotenziv septik shokda ham foydalanish mumkin.[67] Dobutamin ichakka qon quyilishini kamaytirishni o'z ichiga olgan yon ta'siri tufayli epinefrin kabi tez-tez ishlatilmaydi.[67] Bundan tashqari, dobutamin yurak urish tezligini g'ayritabiiy ravishda oshirib, yurak faoliyatini oshiradi.[67]

Ukol

Dan foydalanish steroidlar sepsisda ziddiyatli.[68] Tadqiqotlar qachon va qachon bo'lishiga oid aniq tasavvurni bermaydi glyukokortikoidlar ishlatilishi kerak.[69] 2016 yilda omon qolgan sepsis kampaniyasi past dozani tavsiya qiladi gidrokortizon faqat tomir ichiga yuboriladigan suyuqlik va vazopressorlar septik shokni etarli darajada davolay olmasa.[6] 2019-yilgi Cochrane tekshiruvi past sifatli foyda keltiradigan dalillarni topdi,[11] ikkita ikkita sharh kabi.[12][70]

Og'ir kasallik paytida, holat buyrak usti etishmovchiligi va to'qima qarshiligi kortikosteroidlar sodir bo'lishi mumkin. Bu muddat berilgan tanqidiy kasallik bilan bog'liq kortikosteroid etishmovchiligi.[71] Kortikosteroidlar bilan davolash u bilan kasallanganlarda eng foydali bo'lishi mumkin septik shok va erta og'ir ARDS, boshqalarda uning roli, masalan pankreatit yoki og'ir zotiljam aniq emas.[71] Ammo kortikosteroid etishmovchiligini aniqlashning aniq usuli muammoli bo'lib qolmoqda. Suyuqlik va vazopressorlar bilan reanimatsiyaga yomon ta'sir ko'rsatadiganlarda shubha qilish kerak. Ham ACTH stimulyatsiyasi testi[71] na tasodifiy kortizol tashxisni tasdiqlash uchun darajalar tavsiya etiladi.[6] Glyukokortikoid preparatlarini to'xtatish usuli o'zgaruvchan bo'lib, ular asta-sekin kamaytirilishi yoki shunchaki to'satdan to'xtatilishi kerakligi noma'lum. Ammo, 2016 yilda Surviving Sepsis Kampaniyasi vazopressorlar kerak bo'lmaganda steroidlarni toraytirishni tavsiya qildi.[6]

Anesteziya

Maqsad gelgit hajmi taxmin qilingan tana vaznining 6 ml / kg (PBW) va a plato bosimi 30 sm dan kam H2O talab qiladiganlar uchun tavsiya etiladi shamollatish sepsis tufayli kelib chiqqan og'ir ARDS tufayli. Yuqori ijobiy ekspiratuar bosim (PEEP) sepsisda o'rtacha va og'ir ARDS uchun tavsiya etiladi, chunki u kislorod almashinuvi uchun ko'proq o'pka bo'linmalarini ochadi. Bashorat qilingan tana og'irligi jinsi va bo'yiga qarab hisoblab chiqiladi va buning uchun vositalar mavjud.[72] Qattiq ARDS uchun transpulmoner bosimni qisqartirish orqali ishga yollanish manevrlari zarur bo'lishi mumkin. Ventilyatsiyani yaxshilash uchun iloji bo'lsa, yotoqning boshini ko'tarish tavsiya etiladi. Biroq, β2 adrenergik retseptorlari agonistlari ARDSni davolash tavsiya etilmaydi, chunki u hayot darajasini pasaytirishi va cho'kishi mumkin g'ayritabiiy yurak ritmlari. A o'z-o'zidan nafas olish sinovi foydalanish doimiy havo yo'li bosimi (CPAP), T bo'lagi yoki inspiratuar bosimni oshirish shamollatish muddatini qisqartirishda foydali bo'lishi mumkin. Mexanik shamollatish muddatini qisqartirishda intervalgacha yoki doimiy sedatsiyani minimallashtirish foydalidir.[6]

Yuqumli manbani olib tashlash uchun jarrohlik amaliyotini talab qiladigan sepsisli odamlarga umumiy behushlik qilish tavsiya etiladi. Odatda, inhalatsion va tomir ichiga yuboriladigan anestezikalar qo'llaniladi. Sepsisda anestezikaga bo'lgan talablar kamayishi mumkin. Nafas olish uchun behushlik proinflamatuar sitokinlar darajasini pasaytirishi, leykotsitlarning yopishishini va ko'payishini o'zgartirishi mumkin apoptoz (hujayra o'limi) limfotsitlar, ehtimol toksik ta'sirga ega mitoxondrial funktsiya.[47] Garchi etomidat yurak-qon tomir tizimiga minimal ta'sir ko'rsatadi, ko'pincha yordam berish uchun dori sifatida tavsiya etilmaydi intubatsiya xavotir tufayli bu vaziyatga olib kelishi mumkin buyrak usti bezining yomon ishlashi va o'lim xavfining ortishi.[73][74] Ammo ozgina miqdordagi dalillar etomidat bilan o'lim xavfining o'zgarishini topmagan.[75]

Paralitik moddalar yo'qligida sepsis holatlarida foydalanish tavsiya etilmaydi ARDS, o'sib borayotgan dalillar to'plami, muddatlarning qisqarishini ko'rsatmoqda mexanik shamollatish, ICU va kasalxonada qolish.[10] Biroq, paralitik foydalanish ARDS holatlar munozarali bo'lib qolmoqda. Kerakli ravishda foydalanilganda paralitikalar muvaffaqiyatli mexanik shamollatishga yordam berishi mumkin, ammo shuni ko'rsatadiki, og'ir sepsisdagi mexanik shamollatish kislorod iste'molini va etkazib berishni yaxshilamaydi.[10]

Manba nazorati

Manba nazorati a ni boshqarish uchun jismoniy aralashuvlarni anglatadi infektsiya fokusi va mikroorganizmlarning ko'payishi yoki uy egalarining mudofaasi buzilishi kabi sharoitlarni kamaytirish yiringni drenajlash dan xo'ppoz. Bu yuqumli kasalliklarni nazorat qilishning eng qadimiy protseduralaridan biri bo'lib, lotincha iborani keltirib chiqaradi Ubi yiring, ibi evakua va zamonaviy muolajalar paydo bo'lishiga qaramay muhim bo'lib qolmoqda.[76][77]

Dastlabki maqsadli terapiya

Dastlabki maqsadli terapiya (EGDT) bu tashxis qo'yilganidan keyin dastlabki 6 soat ichida og'ir sepsisni boshqarish usulidir.[78] Bu yurakning oldindan yuklanishini, keyingi yukini va kontraktilligini optimallashtirishga qaratilgan fiziologik maqsadga muvofiq bosqichma-bosqich yondashuv.[79] Bunga erta antibiotiklarni berish kiradi.[79] EGDT shuningdek, 8-12 mm simob ustunida markaziy venoz bosimni, o'rtacha arterial bosimni 65 dan 90 mm gacha, markaziy venoz kislorod bilan to'yinganligini (ScvO) ushlab turishni o'z ichiga olgan asosiy reanimatsiya maqsadlariga erishish uchun gemodinamik parametrlarni va o'ziga xos aralashuvlarni kuzatishni o'z ichiga oladi.2) 70% dan yuqori va siydik miqdori 0,5 ml / kg / soat dan yuqori. Maqsad to'qimalarga kislorod etkazib berishni optimallashtirish va kislorodni tizimli etkazib berish va talab o'rtasidagi muvozanatga erishishdir.[79] Sarumda tegishli pasayish laktat ScvO ga teng bo'lishi mumkin2 va olish osonroq.[80]

Dastlabki sinovda, erta maqsadga yo'naltirilgan terapiya sepsis bilan kasallanganlarda o'limni 46,5% dan 30,5% gacha kamaytirishi aniqlandi,[79] va omon qolgan sepsis kampaniyasi undan foydalanishni tavsiya qilmoqda.[10] Shu bilan birga, yana uchta yirik randomize tekshiruv sinovlari (ProCESS, ARISE va ProMISe), og'ir sepsisdagi standart terapiya bilan taqqoslaganda, erta maqsadga yo'naltirilgan terapiyaning 90 kunlik o'lim foydasini ko'rsatmadi.[81] Ehtimol, EGDTning ba'zi qismlari boshqalarga qaraganda muhimroqdir.[81] Ushbu sinovlardan so'ng EGDT dan foydalanish hali ham oqilona hisoblanadi.[82]

Yangi tug'ilgan chaqaloqlar

Yangi tug'ilgan sepsis tashxis qo'yish qiyin bo'lishi mumkin, chunki yangi tug'ilgan chaqaloqlar asemptomatik bo'lishi mumkin.[83] Agar yangi tug'ilgan chaqaloq sepsisni ko'rsatadigan alomatlar va alomatlarni ko'rsatsa, darhol antibiotiklar boshlanadi va ular diagnostik tekshiruvlar natijasida aniqlangan organizmga yo'naltiriladi yoki simptomlarning yuqumli sabablari bekor qilingandan so'ng to'xtatiladi.[84] Erta aralashuvga qaramay, o'lim septik shokka uchragan bolalarning 13 foizida uchraydi, bu xavf qisman boshqa sog'liq muammolariga asoslangan. Ko'p organ tizimining etishmovchiligi bo'lmagan yoki faqat bitta inotrop agentning o'limini talab qiladiganlar kam.[85]

Boshqalar

Sepsisdagi isitmani, shu jumladan, septik shok holatidagi odamlarni davolash, 28 kun davomida o'lim holatining yaxshilanishi bilan bog'liq emas.[86] Isitmani davolash hali ham boshqa sabablarga ko'ra sodir bo'ladi.[87][88]

2012 yil Cochrane-ni ko'rib chiqish degan xulosaga keldi N-asetilsistein SIRS yoki sepsis bilan kasallanganlarda o'limni kamaytirmaydi va hatto zararli bo'lishi mumkin.[89]

Rekombinant faollashtirilgan oqsil C (drotrecogin alfa ) was originally introduced for severe sepsis (as identified by a high APACHE II score), where it was thought to confer a survival benefit.[78] However, subsequent studies showed that it increased adverse events—bleeding risk in particular—and did not decrease mortality.[90] It was removed from sale in 2011.[90] Another medication known as eritoran also has not shown benefit.[91]

In those with yuqori qon shakar levels, insulin to bring it down to 7.8–10 mmol/L (140–180 mg/dL) is recommended with lower levels potentially worsening outcomes.[92] Glucose levels taken from capillary blood should be interpreted with care because such measurements may not be accurate. If a person has an arterial catheter, arterial blood is recommended for blood glucose testing.[6]

Intermittent or continuous buyrakni almashtirish terapiyasi may be used if indicated. Biroq, natriy gidrokarbonat is not recommended for a person with lactic acidosis secondary to hypoperfusion. Kam molekulyar og'irlikdagi geparin (LMWH), sintez qilinmagan geparin (UFH), and mechanical prophylaxis with vaqti-vaqti bilan pnevmatik siqish devices are recommended for any person with sepsis at moderate to high risk of venous thromboembolism.[6] Stress ulcer prevention with proton-pump inhibitor (PPI) va H2 antagonisti are useful in a person with risk factors of developing upper gastrointestinal bleeding (UGIB) such as on mechanical ventilation for more than 48 hours, coagulation disorders, liver disease, and renal replacement therapy.[6] Achieving partial or full enteral feeding (delivery of nutrients through a oziqlantirish trubkasi ) is chosen as the best approach to provide nutrition for a person who is contraindicated for oral intake or unable to tolerate orally in the first seven days of sepsis when compared to tomir orqali oziqlantirish. Biroq, omega-3 fatty acids are not recommended as immune supplements for a person with sepsis or septic shock. Ning ishlatilishi prokinetik vositalar kabi metoklopramid, domperidon va erythromycin are recommended for those who are septic and unable to tolerate enteral feeding. However, these agents may precipitate prolongation of the QT oralig'i and consequently provoke a qorincha aritmi kabi torsades de pointes. The usage of prokinetic agents should be reassessed daily and stopped if no longer indicated.[6]

Prognoz

Severe sepsis will prove fatal in approximately 20–35% of people, and septic shock will prove fatal in 30–70% of people.[93] Lactate is a useful method of determining prognosis, with those who have a level greater than 4 mmol/L having a mortality of 40% and those with a level of less than 2 mmol/L having a mortality of less than 15%.[30]

There are a number of prognostic stratification systems, such as APACHE II and Mortality in Emergency Department Sepsis. APACHE II factors in the person's age, underlying condition, and various physiologic variables to yield estimates of the risk of dying of severe sepsis. Of the individual covariates, the severity of underlying disease most strongly influences the risk of death. Septic shock is also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and culture-negative severe sepsis. The Mortality in Emergency Department Sepsis (MEDS) score is simpler, and useful in the emergency department environment.[94]

Some people may experience severe long-term cognitive decline following an episode of severe sepsis, but the absence of baseline neuropsychological data in most people with sepsis makes the incidence of this difficult to quantify or to study.[95]

Epidemiologiya

Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized.[4][78] The number of new cases worldwide of sepsis is estimated to be 18 million cases per year.[96] In Qo'shma Shtatlar sepsis affects approximately 3 in 1,000 people,[30] and severe sepsis contributes to more than 200,000 deaths per year.[97]

Sepsis occurs in 1–2% of all hospitalizations and accounts for as much as 25% of ICU bed utilization. Due to it rarely being reported as a primary diagnosis (often being a complication of cancer or other illness), the incidence, mortality, and morbidity rates of sepsis are likely underestimated.[40] Tadqiqot AQSh shtatlari found approximately 651 hospital stays per 100,000 population with a sepsis diagnosis in 2010.[98] It is the second-leading cause of death in non-coronary intensiv terapiya bo'limi (ICU) and the tenth-most-common cause of death overall (the first being heart disease).[99] Children under 12 months of age and elderly people have the highest incidence of severe sepsis.[40] Among people from the U.S. who had multiple sepsis hospital admissions in 2010, those who were discharged to a skilled nursing facility or long-term care following the initial hospitalization were more likely to be readmitted than those discharged to another form of care.[98] A study of 18 U.S. states found that, amongst people with Medicare in 2011, sepsis was the second most common principal reason for readmission within 30 days.[100]

Several medical conditions increase a person's susceptibility to infection and developing sepsis. Common sepsis risk factors include age (especially the very young and old); conditions that weaken the immune system such as saraton, diabet yoki absence of a spleen; va katta travma va burns.[2][101][102]

From 1979 to 2000, data from the United States National Hospital Discharge Survey showed that the incidence of sepsis increased fourfold, to 240 cases per 100,000 population, with higher incidence in men when compared to women. During the same time frame, the in-hospital case fatality rate was reduced from 28% to 18%. However, according to the nationwide inpatient sample from the United States, the incidence of severe sepsis increased from 200 per 10,000 population in 2003 to 300 cases in 2007 for population aged more than 18 years. The incidence rate is particularly high among infants, with the incidence of 500 cases per 100,000 population. Mortality related to sepsis increases with age, from less than 10% in the age group of 3 to 5 years to 60% by sixth decade of life.[21] The increase in average age of the population, alongside the presence of more people with chronic diseases or on immunosupressiv dorilar, and also the increase in the number of invasive procedures being performed, has led to an increased rate of sepsis.[22]

Tarix

Shaxsiylashtirish septikemiya, carrying a spray can marked "Zahar "

The term "σήψις" (sepsis) was introduced by Hippocrates in the fourth century BC, and it meant the process of decay or decomposition of organic matter.[103][104][105] XI asrda, Avitsena used the term "blood rot" for diseases linked to severe yiringli jarayon. Though severe systemic toxicity had already been observed, it was only in the 19th century that the specific term – sepsis – was used for this condition.

The terms "septicemia", also spelled "septicaemia", and "blood poisoning" referred to the microorganisms or their toxins in the blood. The Kasalliklar va ularga tegishli sog'liq muammolarining xalqaro statistik tasnifi (ICD) version 9, which was in use in the US until 2013, used the term septicemia with numerous modifiers for different diagnoses, such as "Streptococcal septicemia".[106] All those diagnoses have been converted to sepsis, again with modifiers, in ICD-10, such as "Sepsis due to streptococcus".[106]

The current terms are dependent on the microorganism that is present: bakteremiya agar bakteriyalar are present in the blood at abnormal levels and are the causative issue, viremia uchun viruslar va fungemia a qo'ziqorin.[107]

By the end of the 19th century, it was widely believed that mikroblar produced substances that could injure the sutemizuvchi host and that soluble toksinlar released during infection caused the fever and shock that were commonplace during severe infections. Pfeiffer atamani o'ylab topdi endotoksin at the beginning of the 20th century to denote the pyrogenic principle associated with Vibrio vabo. It was soon realised that endotoxins were expressed by most and perhaps all grammusbat bakteriyalar. The lipopolisakkarid character of enteric endotoxins was elucidated in 1944 by Shear.[108] The molecular character of this material was determined by Luderitz et al. 1973 yilda.[109]

It was discovered in 1965 that a strain of C3H/HeJ sichqonlar were immune to the endotoxin-induced shock.[110] The genetic locus for this effect was dubbed Lps. These mice were also found to be hypersusceptible to infection by gram-negative bacteria.[111] These observations were finally linked in 1998 by the discovery of the pullik retseptorlari gene 4 (TLR 4).[112] Genetic mapping work, performed over a period of five years, showed that TLR4 was the sole candidate locus within the Lps critical region; this strongly implied that a mutation within TLR4 must account for the lipopolysaccharide resistance phenotype. The defect in the TLR4 gene that led to the endotoxin resistant phenotype was discovered to be due to a mutation in the sitoplazma.[113]

Controversy occurred in the scientific community over the use of mouse models in research into sepsis in 2013, when scientists published a review of the mouse immune system compared to the human immune system, and showed that on a systems level, the two worked very differently; the authors noted that as of the date of their article over 150 clinical trials of sepsis had been conducted in humans, almost all of them supported by promising data in mice, and that all of them had failed. The authors called for abandoning the use of mouse models in sepsis research; others rejected that but called for more caution in interpreting the results of mouse studies[114], and more careful design of preclinical studies.[115][116][117][118] One approach is to rely more on studying biopsies and clinical data from people who have had sepsis, to try to identify biomarkerlar va giyohvandlik maqsadlari for intervention.[119]

Jamiyat va madaniyat

Iqtisodiyot

Sepsis was the most expensive condition treated in United States' hospital stays in 2013, at an aggregate cost of $23.6 billion for nearly 1.3 million hospitalizations.[120] Costs for sepsis hospital stays more than quadrupled since 1997 with an 11.5 percent annual increase.[121] By payer, it was the most costly condition billed to Medicare and the uninsured, the second-most costly billed to Medicaid, and the fourth-most costly billed to xususiy sug'urta.[120]

Ta'lim

A large international collaboration entitled the "Omon qolish Sepsis kampaniyasi " was established in 2002[122] to educate people about sepsis and to improve outcomes with sepsis. The Campaign has published an evidence-based review of management strategies for severe sepsis, with the aim to publish a complete set of guidelines in subsequent years.[78]

Sepsis alyansi is a charitable organization that was created to raise sepsis awareness among both the general public and healthcare professionals.[123]

Tadqiqot

Phenotypic strategy switches of microbes capable of provoking sepsis

Some authors suggest that initiating sepsis by the normally mututeristik (or neutral) members of the mikrobiom may not always be an accidental side effect of the deteriorating host immune system. Rather it is often an moslashuvchan microbial response to a sudden decline of host survival chances. Under this scenario, the microbe species provoking sepsis benefit from monopolizing the future cadaver, utilizing its biomass as decomposers, and then transmitting through soil or water to establish mutualistic relations with new individuals. Bakteriyalar Streptokokk pnevmoniyasi, Escherichia coli, Proteus spp., Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella spp., Klostridium spp., Laktobatsillus spp., Bacteroides spp. and the fungi Candida spp. are all capable of such a high level of phenotypic plasticity. Evidently, not all cases of sepsis arise through such adaptive microbial strategy switches.[124]

Adabiyotlar

  1. ^ "Blood Culture Collection" (PDF). WVUH Laboratories. 2012 yil 7 aprel. Olingan 23 mart 2020.
  2. ^ a b v d e f g h men j "Sepsis Questions and Answers". cdc.gov. Kasalliklarni nazorat qilish va oldini olish markazlari (CDC). 2014 yil 22-may. Arxivlandi asl nusxasidan 2014 yil 4 dekabrda. Olingan 28 noyabr 2014.
  3. ^ a b v d e f g h men j k Jui J, et al. (American College of Emergency Physicians ) (2011). "Ch. 146: Septic Shock". In Tintinalli JE, et al. (tahr.). Tintinalli shoshilinch tibbiyoti: keng qamrovli o'quv qo'llanma (7-nashr). Nyu York: McGraw-Hill. pp. 1003–14. ISBN  9780071484800.
  4. ^ a b v Deutschman CS, Tracey KJ (April 2014). "Sepsis: Current dogma and new perspectives". Immunitet. 40 (4): 463–75. doi:10.1016 / j.immuni.2014.04.001. PMID  24745331.
  5. ^ a b v d e f g h Singer M, Deutschman CS, et al. (2016 yil fevral). "Sepsis va septik shok uchun uchinchi xalqaro konsensus ta'riflari (sepsis-3)". JAMA. 315 (8): 801–10. doi:10.1001 / jama.2016.0287. PMC  4968574. PMID  26903338.
  6. ^ a b v d e f g h men j k l m n o p q r s t siz v w x y z aa ab ak Rhodes A, Evans LE, et al. (March 2017). "Omon qolgan sepsis kampaniyasi: Sepsis va septik shokni boshqarish bo'yicha xalqaro ko'rsatmalar: 2016". Reanimatsiya tibbiyoti. 43 (3): 304–377. doi:10.1007/s00134-017-4683-6. PMID  28101605.
  7. ^ a b v d e Jawad I, Lukšić I, et al. (Iyun 2012). "Assessing available information on the burden of sepsis: Global estimates of incidence, prevalence and mortality". Global Health jurnali. 2 (1): 010404. doi:10.7189/jogh.01.010404. PMC  3484761. PMID  23198133.
  8. ^ a b v Martin GS (June 2012). "Sepsis, severe sepsis and septic shock: Changes in incidence, pathogens and outcomes". Infektsiyaga qarshi terapiyani ekspertizasi. 10 (6): 701–6. doi:10.1586/eri.12.50. PMC  3488423. PMID  22734959.
  9. ^ a b v Chao C, Muming Y, Yanfen C (2019). "Pathological Alteration and Therapeutic Implications of Sepsis-Induced Immune Cell Apoptosis". Hujayra o'limi va kasallik. 10 (10): 782. doi:10.1038/s41419-019-2015-1. PMC  6791888. PMID  31611560.
  10. ^ a b v d e f g h men j k l m n o p q r s t siz v w x y Dellinger RP, Levy MM, et al. (2013 yil fevral). "Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012". Muhim tibbiyot. 41 (2): 580–637. doi:10.1097 / CCM.0b013e31827e83af. PMID  23353941.
  11. ^ a b Annane, D; Bellissant, E; Bollaert, PE; Briegel, J; Keh, D; Kupfer, Y; Pirracchio, R; Rochwerg, B (6 December 2019). "Corticosteroids for treating sepsis in children and adults". Tizimli sharhlarning Cochrane ma'lumotlar bazasi. 12: CD002243. doi:10.1002/14651858.CD002243.pub4. PMC  6953403. PMID  31808551.
  12. ^ a b Fang F, Zhang Y, et al. (February 2019). "Association of corticosteroid treatment with outcomes in adult patients with sepsis: A systematic review and meta-analysis". JAMA ichki kasalliklar. 179 (2): 213–223. doi:10.1001/jamainternmed.2018.5849. PMC  6439648. PMID  30575845.
  13. ^ Long B, Koyfman A (November 2017). "Controversies in corticosteroid use for sepsis". Shoshilinch tibbiy yordam jurnali. 53 (5): 653–661. doi:10.1016/j.jemermed.2017.05.024. PMID  28916121.
  14. ^ Rudd, Kristina E; Johnson, Sarah Charlotte; Agesa, Kareha M; Shackelford, Katya Anne; Tsoi, Derrick; Kievlan, Daniel Rhodes; Colombara, Danny V; Ikuta, Kevin S; Kissoon, Niranjan; Finfer, Simon; Fleischmann-Struzek, Carolin; Machado, Flavia R; Reinhart, Konrad K; Rouan, Ketrin; Seymour, Christopher W; Watson, R Scott; West, T Eoin; Marinyo, Fotima; Hay, Simon I; Lozano, Rafael; Lopez, Alan D; Angus, Derek C; Myurrey, Kristofer J L; Naghavi, Mohsen (January 2020). "Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study". Lanset. 395 (10219): 200–211. doi:10.1016/S0140-6736(19)32989-7. PMC  6970225. PMID  31954465.
  15. ^ a b Angus DC, van der Poll T (August 2013). "Severe sepsis and septic shock". Nyu-England tibbiyot jurnali. 369 (9): 840–51. doi:10.1056 / NEJMra1208623. PMID  23984731. Xulosa (2013 yil 30-avgust).
  16. ^ a b v Bone RC, Balk RA va boshq. (ACCP / SCCM konsensus konferentsiyasi qo'mitasi. American College of Chest Physicians /Muhim tibbiyot tibbiyoti jamiyati ) (1992 yil iyun). "Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis". Ko'krak qafasi. 101 (6): 1644–55. doi:10.1378 / ko'krak qafasi.101.6.1644. PMID  1303622. Septicemia... has been used... in a variety of ways... We therefore suggest that this term be eliminated from current usage.
  17. ^ a b Levy MM, Fink MP, et al. (April 2003). "2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference" (PDF). Muhim tibbiyot. 31 (4): 1250–6. doi:10.1097/01.CCM.0000050454.01978.3B. PMID  12682500. S2CID  19605781. Arxivlandi (PDF) asl nusxasidan 2015 yil 24 sentyabrda.
  18. ^ a b Felner K, Smith RL (2012). "Ch. 138: Sepsis". In McKean S, et al. (tahr.). Kasalxona tibbiyotining printsiplari va amaliyoti. Nyu York: McGraw-Hill. pp. 1099–109. ISBN  978-0071603898.
  19. ^ a b v d e Gauer, RL (1 July 2013). "Early recognition and management of sepsis in adults: the first six hours". Amerika oilaviy shifokori. 88 (1): 44–53. PMID  23939605.
  20. ^ MedlinePlus Encyclopedia: Sepsis. Retrieved 29 November 2014.
  21. ^ a b v d Munford RS, Suffredini AF (2014). "Ch. 75: Sepsis, Severe Sepsis and Septic Shock". In Bennett JE, et al. (tahr.). Mandell, Duglas va Bennettning yuqumli kasalliklarga oid printsiplari va amaliyoti (8-nashr). Filadelfiya: Elsevier sog'liqni saqlash fanlari. pp. 914–34. ISBN  9780323263733.
  22. ^ a b v Polat G, Ugan RA, et al. (2017 yil fevral). "Sepsis and septic shock: Current treatment strategies and new approaches". Evroosiyo tibbiyot jurnali. 49 (1): 53–8. doi:10.5152/eurasianjmed.2017.17062. PMC  5389495. PMID  28416934.
  23. ^ Bloch KC (2009). "Ch. 4: Infectious Diseases". In McPhee SJ, et al. (tahr.). Pathophysiology of Disease (6-nashr). Nyu York: McGraw-Hill. ISBN  9780071621670.
  24. ^ Ramachandran G (January 2014). "Gram-positive and gram-negative bacterial toxins in sepsis: A brief review". Virusli kasallik. 5 (1): 213–8. doi:10.4161/viru.27024. PMC  3916377. PMID  24193365.
  25. ^ Delaloye J, Calandra T (January 2014). "Invasive candidiasis as a cause of sepsis in the critically ill patient". Virusli kasallik. 5 (1): 161–9. doi:10.4161/viru.26187. PMC  3916370. PMID  24157707.
  26. ^ Harris R (22 February 2018). "Synergy Between Nurses And Automation Could Be Key To Finding Sepsis Early". Hamma narsa ko'rib chiqildi. Milliy radio. Arxivlandi asl nusxasidan 2018 yil 27 fevralda. Olingan 26 fevral 2018.
  27. ^ a b v Wacker C, Prkno A, et al. (May 2013). "Procalcitonin as a diagnostic marker for sepsis: A systematic review and meta-analysis". Lanset yuqumli kasalliklar. 13 (5): 426–35. doi:10.1016/S1473-3099(12)70323-7. PMID  23375419.
  28. ^ Morris E, McCartney D, et al. (Dekabr 2017). "Point-of-care lactate testing for sepsis at presentation to health care: A systematic review of patient outcomes". Britaniyaning umumiy amaliyot jurnali. 67 (665): e859–70. doi:10.3399/bjgp17X693665. PMC  5697556. PMID  29158243.
  29. ^ Bone RC, Balk RA va boshq. (ACCP / SCCM konsensus konferentsiyasi qo'mitasi. American College of Chest Physicians /Muhim tibbiyot tibbiyoti jamiyati ) (1992 yil iyun). "Sepsis va organ etishmovchiligining ta'riflari va sepsisda innovatsion davolash usullaridan foydalanish bo'yicha ko'rsatmalar". Ko'krak qafasi. 101 (6): 1644–55. doi:10.1378 / ko'krak qafasi.101.6.1644. PMID  1303622.
  30. ^ a b v d Soong J, Soni N (June 2012). "Sepsis: Recognition and treatment". Klinik tibbiyot. 12 (3): 276–80. doi:10.7861/clinmedicine.12-3-276. PMC  4953494. PMID  22783783.
  31. ^ Simpson SQ (May 2016). "New sepsis criteria: A change we should not make". Ko'krak qafasi. 149 (5): 1117–8. doi:10.1016/j.chest.2016.02.653. PMID  26927525. We believe that adopting a more restrictive definition that requires further progression along the sepsis pathway may delay intervention in this highly time-dependent condition, with additional risk to patients.
  32. ^ Vincent JL, Martin GS, et al. (July 2016). "qSOFA does not replace SIRS in the definition of sepsis". Muhim parvarish. 20 (1): 210. doi:10.1186/s13054-016-1389-z. PMC  4947518. PMID  27423462. We hope this editorial will clarify that the qSOFA is meant to be used to raise suspicion of sepsis and prompt further action—it is not a replacement for SIRS and is not part of the definition of sepsis.
  33. ^ Fernando SM, Tran A, et al. (2018 yil fevral). "Prognostic accuracy of the quick Sequential Organ Failure Assessment for mortality in patients with suspected infection: A systematic review and meta-analysis". Ichki tibbiyot yilnomalari. 168 (4): 266–75. doi:10.7326/M17-2820. PMID  29404582. S2CID  3441582.
  34. ^ Abraham E, Singer M (October 2007). "Mechanisms of sepsis-induced organ dysfunction". Muhim tibbiyot. 35 (10): 2408–16. doi:10.1097/01.CCM.0000282072.56245.91. PMID  17948334. S2CID  12657048.
  35. ^ Goldstein B, Giroir B, et al. (2005 yil yanvar). "International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics". Bolalar uchun muhim tibbiy yordam. 6 (1): 2–8. doi:10.1097/01.PCC.0000149131.72248.E6. PMID  15636651. S2CID  8190072.
  36. ^ a b Backes Y, van der Sluijs KF, et al. (Sentyabr 2012). "Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: A systematic review". Reanimatsiya tibbiyoti. 38 (9): 1418–28. doi:10.1007/s00134-012-2613-1. PMC  3423568. PMID  22706919.
  37. ^ Mayr FB, Yende S, et al. (January 2014). "Epidemiology of severe sepsis". Virusli kasallik. 5 (1): 4–11. doi:10.4161/viru.27372. PMC  3916382. PMID  24335434.
  38. ^ Machowicz R, Janka G, et al. (Iyun 2017). "Similar but not the same: Differential diagnosis of HLH and sepsis". Onkologiya / gematologiya bo'yicha tanqidiy sharhlar. 114: 1–12. doi:10.1016/j.critrevonc.2017.03.023. PMID  28477737.
  39. ^ a b Satar M, Ozlü F (September 2012). "Neonatal sepsis: A continuing disease burden" (PDF). Turkiya pediatriya jurnali. 54 (5): 449–57. PMID  23427506. Arxivlandi asl nusxasi (PDF) 2014 yil 19 dekabrda.
  40. ^ a b v d e f g Ely EW, Goyette RE (2005). "Ch. 46: Sepsis with Acute Organ Dysfunction". In Hall JB, et al. (tahr.). Principles of Critical Care (3-nashr). Nyu York: McGraw-Hill tibbiyoti. ISBN  978-0071416405.
  41. ^ Shukla P, Rao GM, et al. (2014 yil noyabr). "Therapeutic interventions in sepsis: Current and anticipated pharmacological agents". Britaniya farmakologiya jurnali. 171 (22): 5011–31. doi:10.1111/bph.12829. PMC  4253453. PMID  24977655.
  42. ^ Park BS, Lee JO (December 2013). "Recognition of lipopolysaccharide pattern by TLR4 complexes". Eksperimental va molekulyar tibbiyot. 45 (12): e66. doi:10.1038/emm.2013.97. PMC  3880462. PMID  24310172.
  43. ^ Cross AS (January 2014). "Anti-endotoxin vaccines: Back to the future". Virusli kasallik. 5 (1): 219–25. doi:10.4161/viru.25965. PMC  3916378. PMID  23974910.
  44. ^ Fournier B, Philpott DJ (July 2005). "Recognition of Staphylococcus aureus by the innate immune system". Klinik mikrobiologiya sharhlari. 18 (3): 521–40. doi:10.1128/CMR.18.3.521-540.2005. PMC  1195972. PMID  16020688.
  45. ^ Leentjens J, Kox M, et al. (Iyun 2013). "Immunotherapy for the adjunctive treatment of sepsis: From immunosuppression to immunostimulation. Time for a paradigm change?". Amerika nafas olish va tanqidiy tibbiyot jurnali. 187 (12): 1287–93. doi:10.1164/rccm.201301-0036CP. PMID  23590272.
  46. ^ Antonopoulou A, Giamarellos-Bourboulis EJ (January 2011). "Immunomodulation in sepsis: State of the art and future perspective". Immunoterapiya. 3 (1): 117–28. doi:10.2217/imt.10.82. PMID  21174562.
  47. ^ a b v Yuki K, Murakami N (6 January 2016). "Sepsis pathophysiology and anesthetic consideration". Kardiyovasküler va gematologik kasalliklar Dori vositalari maqsadlari. 15 (1): 57–69. doi:10.2174/1871529x15666150108114810. PMC  4704087. PMID  25567335.
  48. ^ Fujishima S (1 November 2016). "Organ dysfunction as a new standard for defining sepsis". Yallig'lanish va tiklanish. 36 (24): 24. doi:10.1186/s41232-016-0029-y. PMC  5725936. PMID  29259697.
  49. ^ Nimah M, Brilli RJ (July 2003). "Coagulation dysfunction in sepsis and multiple organ system failure". Muhim yordam klinikalari. 19 (3): 441–58. doi:10.1016/s0749-0704(03)00008-3. PMID  12848314.
  50. ^ a b Marik PE (June 2014). "Iatrogenic salt water drowning and the hazards of a high central venous pressure". Reanimatsiya yilnomasi. 4: 21. doi:10.1186/s13613-014-0021-0. PMC  4122823. PMID  25110606.
  51. ^ a b v d Marik PE (June 2014). "Early management of severe sepsis: Concepts and controversies". Ko'krak qafasi. 145 (6): 1407–18. CiteSeerX  10.1.1.661.7518. doi:10.1378/chest.13-2104. PMID  24889440.
  52. ^ Daniels R (April 2011). "Surviving the first hours in sepsis: Getting the basics right (an intensivist's perspective)" (PDF). Antimikrobiyal kimyoterapiya jurnali. 66 (Suppl 2): ii11–23. doi:10.1093/jac/dkq515. PMID  21398303.
  53. ^ Shotlandiya kollejlararo ko'rsatmalar tarmog'i (SIGN) (2014 yil may). Care of Deteriorating Patients (PDF). Guideline 139. Edinburgh: SIGN. ISBN  978-1-909103-26-9. Arxivlandi asl nusxasi (PDF) 2014 yil 11-avgustda. Olingan 6 dekabr 2014.
  54. ^ Sterling SA, Miller WR, et al. (Sentyabr 2015). "The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: A systematic review and meta-Analysis". Muhim tibbiyot. 43 (9): 1907–15. doi:10.1097/CCM.0000000000001142. PMC  4597314. PMID  26121073.
  55. ^ Roberts JA, Abdul-Aziz MH, et al. (2016 yil sentyabr). "Continuous versus intermittent β-Lactam infusion in severe sepsis. A meta-analysis of individual patient data from randomized trials". Amerika nafas olish va tanqidiy tibbiyot jurnali. 194 (6): 681–91. doi:10.1164/rccm.201601-0024oc. PMID  26974879.
  56. ^ de Caen AR, Berg MD, et al. (Noyabr 2015). "Part 12: Pediatric Advanced Life Support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care". Sirkulyatsiya. 132 (18 ta qo'shimcha 2): S526-42. doi:10.1161 / cir.0000000000000266. PMC  6191296. PMID  26473000.
  57. ^ a b v Lewis SR, Pritchard MW, et al. (2018 yil avgust). "Kolloidlar og'ir holatlarda suyuqlikni reanimatsiya qilish uchun kristalloidlarga nisbatan". Tizimli sharhlarning Cochrane ma'lumotlar bazasi. 8: CD000567. doi:10.1002 / 14651858.CD000567.pub7. PMC  6513027. PMID  30073665.
  58. ^ Zarychanski R, Abou-Setta AM, et al. (2013 yil fevral). "Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: A systematic review and meta-analysis". JAMA. 309 (7): 678–88. doi:10.1001 / jama.2013.430. PMID  23423413.
  59. ^ Haase N, Perner A, et al. (2013 yil fevral). "Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: Systematic review with meta-analysis and trial sequential analysis". BMJ. 346: f839. doi:10.1136/bmj.f839. PMC  3573769. PMID  23418281.
  60. ^ Serpa Neto A, Veelo DP, et al. (2014 yil fevral). "Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney injury and use of renal replacement therapy: A systematic review and meta-analysis of the literature". Journal of Critical Care. 29 (1): 185.e1–7. doi:10.1016/j.jcrc.2013.09.031. PMID  24262273.
  61. ^ Patel A, Laffan MA, et al. (2014 yil iyul). "Randomised trials of human albumin for adults with sepsis: Systematic review and meta-analysis with trial sequential analysis of all-cause mortality". BMJ. 349: g4561. doi:10.1136/bmj.g4561. PMC  4106199. PMID  25099709.
  62. ^ Holst LB, Haase N, et al. (October 2014). "Lower versus higher hemoglobin threshold for transfusion in septic shock". Nyu-England tibbiyot jurnali. 371 (15): 1381–91. doi:10.1056/NEJMoa1406617. PMID  25270275. S2CID  16280618.
  63. ^ a b Alejandria MM, Lansang MA, et al. (2013 yil sentyabr). "Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock". Tizimli sharhlarning Cochrane ma'lumotlar bazasi. 9 (9): CD001090. doi:10.1002/14651858.CD001090.pub2. PMC  6516813. PMID  24043371.
  64. ^ Bai, X; Yu, V; Dji, V; Lin, Z; Tan, S; Duan, K; Dong, Y; Xu, L; Li, N (3 October 2014). "Early versus delayed administration of norepinephrine in patients with septic shock". Muhim parvarish. 18 (5): 532. doi:10.1186/s13054-014-0532-y. PMC  4194405. PMID  25277635.
  65. ^ a b Avni T, Lador A, et al. (2015). "Vasopressors for the treatment of septic shock: Systematic review and meta-analysis". PLOS One. 10 (8): e0129305. Bibcode:2015PLoSO..1029305A. doi:10.1371/journal.pone.0129305. PMC  4523170. PMID  26237037.
  66. ^ a b Hamzaoui O, Scheeren TW, et al. (2017 yil avgust). "Norepinephrine in septic shock: When and how much?". Tanqidiy g'amxo'rlikning dolzarb fikri. 23 (4): 342–7. doi:10.1097/mcc.0000000000000418. PMID  28509668. S2CID  2078670.
  67. ^ a b v Dubin A, Lattanzio B, et al. (2017). "The spectrum of cardiovascular effects of dobutamine - from healthy subjects to septic shock patients". Revista Brasileira de Terapia Intensiva. 29 (4): 490–8. doi:10.5935/0103-507x.20170068. PMC  5764562. PMID  29340539.
  68. ^ Patel GP, Balk RA (January 2012). "Systemic steroids in severe sepsis and septic shock". Amerika nafas olish va tanqidiy tibbiyot jurnali. 185 (2): 133–9. doi:10.1164/rccm.201011-1897CI. PMID  21680949.
  69. ^ Volbeda M, Wetterslev J, et al. (2015 yil iyul). "Glucocorticosteroids for sepsis: Systematic review with meta-analysis and trial sequential analysis". Reanimatsiya tibbiyoti. 41 (7): 1220–34. doi:10.1007/s00134-015-3899-6. PMC  4483251. PMID  26100123.
  70. ^ Ni YN, Liu YM, et al. (Sentyabr 2019). "Can corticosteroids reduce the mortality of patients with severe sepsis? A systematic review and meta-analysis". Amerika shoshilinch tibbiy yordam jurnali. 37 (9): 1657–64. doi:10.1016/j.ajem.2018.11.040. PMID  30522935.
  71. ^ a b v Marik PE, Pastores SM, et al. (June 2008). "Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine". Muhim tibbiyot. 36 (6): 1937–49. doi:10.1097/CCM.0b013e31817603ba. PMID  18496365. S2CID  7861625.
  72. ^ NHLBI–NIH ARDS Network (2014). "Asboblar". ardsnet.org. Milliy yurak, o'pka va qon instituti (NHLBI), Milliy sog'liqni saqlash institutlari (NIH). Arxivlandi asl nusxasidan 2019 yil 3 dekabrda.
  73. ^ Cherfan AJ, Arabi YM, et al. (2012 yil may). "Advantages and disadvantages of etomidate use for intubation of patients with sepsis". Pharmacotherapy. 32 (5): 475–82. doi:10.1002/j.1875-9114.2012.01027.x. PMID  22488264.
  74. ^ Chan CM, Mitchell AL, et al. (November 2012). "Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis*". Muhim tibbiyot. 40 (11): 2945–53. doi:10.1097/CCM.0b013e31825fec26. PMID  22971586. S2CID  916535.
  75. ^ Gu WJ, Wang F, et al. (2015 yil fevral). "Single-dose etomidate does not increase mortality in patients with sepsis: A systematic review and meta-analysis of randomized controlled trials and observational studies". Ko'krak qafasi. 147 (2): 335–46. doi:10.1378/chest.14-1012. PMID  25255427. S2CID  22739840.
  76. ^ Lagunes, Leonel; Encina, Belen; Ramirez-Estrada, Sergio (September 2016). "Current understanding in source control management in septic shock patients: a review". Annals of Translational Medicine. 4 (17): 330. doi:10.21037/atm.2016.09.02. ISSN  2305-5839. PMC  5050189. PMID  27713888.
  77. ^ De Waele, J. J.; Malbrain, M. M. L. G.; De Laet, I. E. (2009), Vincent, Jean-Louis (ed.), "Source Control in the ICU", Reanimatsiya va shoshilinch tibbiy yordam yilnomasi, Springer Berlin Heidelberg, pp. 93–101, doi:10.1007/978-3-540-92276-6_9, ISBN  978-3-540-92275-9
  78. ^ a b v d Dellinger RP, Levy MM, et al. (2008 yil yanvar). "Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008". Reanimatsiya tibbiyoti. 34 (1): 17–60. doi:10.1007/s00134-007-0934-2. PMC  2249616. PMID  18058085.
  79. ^ a b v d Rivers E, Nguyen B va boshq. (November 2001). "Og'ir sepsis va septik shokni davolashda maqsadga yo'naltirilgan erta terapiya". Nyu-England tibbiyot jurnali. 345 (19): 1368–77. doi:10.1056 / NEJMoa010307. PMID  11794169.
  80. ^ Fuller BM, Dellinger RP (June 2012). "Lactate as a hemodynamic marker in the critically ill". Tanqidiy g'amxo'rlikning dolzarb fikri. 18 (3): 267–72. doi:10.1097/MCC.0b013e3283532b8a. PMC  3608508. PMID  22517402.
  81. ^ a b Dell'Anna AM, Taccone FS (October 2015). "Early-goal directed therapy for septic shock: Is it the end?". Minerva Anestesiologica. 81 (10): 1138–43. PMID  26091011.
  82. ^ Rusconi AM, Bossi I, et al. (Sentyabr 2015). "Early goal-directed therapy vs usual care in the treatment of severe sepsis and septic shock: A systematic review and meta-analysis". Ichki va shoshilinch tibbiy yordam. 10 (6): 731–43. doi:10.1007/s11739-015-1248-y. PMID  25982917. S2CID  207311061.
  83. ^ Shane AL, Stoll BJ (January 2014). "Neonatal sepsis: Progress towards improved outcomes". Infektsiya jurnali. 68 (Suppl 1): S24–32. doi:10.1016/j.jinf.2013.09.011. PMID  24140138.
  84. ^ Camacho-Gonzalez A, Spearman PW, et al. (2013 yil aprel). "Neonatal infectious diseases: Evaluation of neonatal sepsis". Shimoliy Amerikaning pediatriya klinikalari. 60 (2): 367–89. doi:10.1016/j.pcl.2012.12.003. PMC  4405627. PMID  23481106.
  85. ^ Kutko MC, Calarco MP, et al. (July 2003). "Mortality rates in pediatric septic shock with and without multiple organ system failure". Bolalar uchun muhim tibbiy yordam. 4 (3): 333–7. doi:10.1097/01.PCC.0000074266.10576.9B. PMID  12831416. S2CID  18089789.
  86. ^ Drewry AM, Ablordeppey EA, et al. (2017 yil may). "Antipyretic therapy in critically ill septic patients: A systematic review and meta-analysis". Muhim tibbiyot. 45 (5): 806–13. doi:10.1097 / CCM.0000000000002285. PMC  5389594. PMID  28221185.
  87. ^ Niven DJ, Laupland KB, et al. (2013 yil dekabr). "Diagnosis and management of temperature abnormality in ICUs: A EUROBACT investigators' survey". Muhim parvarish. 17 (6): R289. doi:10.1186/cc13153. PMC  4057370. PMID  24326145.
  88. ^ Launey Y, Nesseler N, et al. (2011). "Clinical Review: Fever in septic ICU patients--friend or foe?". Muhim parvarish. 15 (3): 222. doi:10.1186/cc10097. PMC  3218963. PMID  21672276.
  89. ^ Szakmany T, Hauser B, et al. (Sentyabr 2012). "N-acetylcysteine for sepsis and systemic inflammatory response in adults". Tizimli sharhlarning Cochrane ma'lumotlar bazasi. 9 (9): CD006616. doi:10.1002/14651858.CD006616.pub2. PMC  6517277. PMID  22972094.
  90. ^ a b Martí-Carvajal AJ, Solà I, et al. (2012 yil dekabr). "Katta yoshdagi va pediatrik bemorlarda og'ir sepsis va septik shok uchun odamning rekombinant oqsillari S". Tizimli sharhlarning Cochrane ma'lumotlar bazasi. 12: CD004388. doi:10.1002 / 14651858.CD004388.pub6. PMC  6464614. PMID  23235609.
  91. ^ Fink MP, Warren HS (October 2014). "Strategies to improve drug development for sepsis". Nature Reviews Drug Discovery. 13 (10): 741–58. doi:10.1038/nrd4368. PMID  25190187. S2CID  20904332.
  92. ^ Hirasawa H, Oda S, et al. (Sentyabr 2009). "Og'ir sepsis va septik shok bilan og'rigan bemorlarda qon glyukoza nazorati". Jahon Gastroenterologiya jurnali. 15 (33): 4132–6. doi:10.3748 / wjg.15.4132. PMC  2738808. PMID  19725146.
  93. ^ Rassel JA (oktyabr 2008). "Hozirgi septik shokni boshqarish". Minerva Medika. 99 (5): 431–58. PMID  18971911.
  94. ^ Carpenter CR, Keim SM va boshq. (Oktyabr 2009). "Favqulodda vaziyatlar bo'limida potentsial septik bemorning xavf-xatar tabaqalanishi: Favqulodda vaziyatlar bo'limi sepsisidagi o'lim (MEDS)". Shoshilinch tibbiy yordam jurnali. 37 (3): 319–27. doi:10.1016 / j.jemermed.2009.03.016. PMID  19427752.
  95. ^ Jekson JK, Xopkins RO va boshqalar. (2009 yil noyabr). "O'tkir nafas qisilishi sindromi, sepsis va kognitiv pasayish: qayta ko'rib chiqish va amaliy tadqiqotlar". Southern Medical Journal. 102 (11): 1150–7. doi:10.1097 / SMJ.0b013e3181b6a592. PMC  3776422. PMID  19864995.
  96. ^ Lyle NH, Pena OM va boshq. (2014 yil sentyabr). "Sepsisni samarali davolashda to'siqlar: mikroblarga qarshi vositalar, sepsis ta'riflari va mezbonga yo'naltirilgan davolash usullari". Nyu-York Fanlar akademiyasining yilnomalari. 1323 (2014): 101–14. Bibcode:2014NYASA1323..101L. doi:10.1111 / nyas.12444. PMID  24797961.
  97. ^ Munford RS (2011). "Ch. 271: Kuchli sepsis va septik shok". Longo DL va boshq. (tahr.). Xarrisonning ichki kasallik tamoyillari (18-nashr). Nyu York: McGraw-Hill. 2223-31 betlar. ISBN  9780071748896.
  98. ^ a b Satton JP, Fridman B (sentyabr 2013). "Tanlangan HCUP shtatlaridagi septikemiya kasalxonasiga yotqizish tendentsiyalari va qayta qabul qilish, 2005 va 2010 yillar". Sog'liqni saqlash xarajatlari va ulardan foydalanish loyihasi. 161-sonli statistik ma'lumot. Amerika Qo'shma Shtatlarining Milliy tibbiyot kutubxonasi. PMID  24228290. Arxivlandi asl nusxasidan 2017 yil 6 sentyabrda.
  99. ^ Martin GS, Mannino DM va boshq. (2003 yil aprel). "1979 yildan 2000 yilgacha AQShda sepsis epidemiologiyasi". Nyu-England tibbiyot jurnali. 348 (16): 1546–54. doi:10.1056 / NEJMoa022139. PMID  12700374.
  100. ^ Hines AL, Barrett ML va boshq. (2014 yil aprel). "To'lovchilar tomonidan kattalar kasalxonasida eng ko'p qabul qilinadigan sharoitlar, 2011 yil". Sog'liqni saqlash xarajatlari va ulardan foydalanish loyihasi. 172-sonli statistik ma'lumot. Sog'liqni saqlash tadqiqotlari va sifat agentligi: Amerika Qo'shma Shtatlarining Milliy tibbiyot kutubxonasi. PMID  24901179. Arxivlandi asl nusxasidan 2016 yil 4 martda.
  101. ^ Koh GC, Peacock SJ va boshq. (Aprel 2012). "Qandli diabetning sepsis patogeneziga ta'siri". Evropa klinik mikrobiologiya va yuqumli kasalliklar jurnali. 31 (4): 379–88. doi:10.1007 / s10096-011-1337-4. PMC  3303037. PMID  21805196.
  102. ^ Rubin LG, Schaffner V (2014 yil iyul). "Klinik amaliyot: asplenik bemorni parvarish qilish". Nyu-England tibbiyot jurnali. 371 (4): 349–56. doi:10.1056 / NEJMcp1314291. PMID  25054718.
  103. ^ Geroulanos S, Douka ET (2006 yil dekabr). "So'zning tarixiy istiqboli" sepsis"". Reanimatsiya tibbiyoti. 32 (12): 2077. doi:10.1007 / s00134-006-0392-2. PMID  17131165. S2CID  37084190.
  104. ^ Vinsent J (2008). "Ch. 1: Sepsis va yuqumsiz SIRS ta'rifi". Cavaillon J va boshq. (tahr.). Sepsis va yuqumli bo'lmagan tizimli yallig'lanish: biologiyadan muhim parvarishgacha. John Wiley & Sons. p. 3. ISBN  9783527319350.
  105. ^ Marshall JK (2008 yil mart). "Sepsis: Klinik tadqiqotlarga yondashuvni qayta ko'rib chiqish". Leykotsitlar biologiyasi jurnali. 83 (3): 471–82. CiteSeerX  10.1.1.492.7774. doi:10.1189 / jlb.0607380. PMID  18171697.
  106. ^ a b Styuart, Sintiya. "ICD-10 sepsis kodlashni qanday kengaytirayotganini tushunib oling - AAPC bilim markazi". AAPC. Olingan 6 fevral 2020.
  107. ^ "Bakteremiya". Merck qo'llanmasi - uy sharoitida sog'liq uchun qo'llanma. Merck & Co. Arxivlandi asl nusxasidan 2017 yil 28 iyuldagi. Olingan 25 noyabr 2017.
  108. ^ Shear MJ (1944). "Shishlarni kimyoviy davolash, IX: Sichqonlarning qon ketishini hosil qiluvchi bakterial polisaxaridni quyish uchun birlamchi teri osti o'smalari bilan reaktsiyasi". Milliy saraton instituti jurnali. 4 (5): 461–76. doi:10.1093 / jnci / 4.5.461.
  109. ^ Lyuderits O, Galanos S va boshqalar. (1973). "Lipid A: kimyoviy tuzilishi va biologik faolligi". Yuqumli kasalliklar jurnali. 128: S17 – S29. doi:10.1093 / infdis / 128.Supplement_1.S17. JSTOR  30106029. PMID  4352586.
  110. ^ Xeppner G, Vayss DW (1965 yil sentyabr). "Sichqon sichqonlarining endotoksin va endotoksin-qizil qon hujayralari aralashmalariga yuqori sezuvchanligi". Bakteriologiya jurnali. 90 (3): 696–703. doi:10.1128 / JB.90.3.696-703.1965. PMC  315712. PMID  16562068.
  111. ^ O'Brien AD, Rozenstreich DL va boshq. (1980 yil yanvar). "Sichqonlarda Salmonella typhimurium sezuvchanligini genetik nazorat: LPS genining roli". Immunologiya jurnali. 124 (1): 20–4. PMID  6985638.
  112. ^ Poltorak A, Smirnova I va boshqalar. (Sentyabr 1998). "Lps lokusining genetik va fizik xaritasi: kritik mintaqada toll-4 retseptorlarini nomzod gen sifatida aniqlash". Qon hujayralari, molekulalar va kasalliklar. 24 (3): 340–55. doi:10.1006 / bcmd.1998.0201. PMID  10087992.
  113. ^ Poltorak A, He X va boshq. (1998 yil dekabr). "C3H / HeJ va C57BL / 10ScCr sichqonlarida nuqsonli LPS signalizatsiyasi: Tlr4 genidagi mutatsiyalar". Ilm-fan. 282 (5396): 2085–8. Bibcode:1998 yil ... 282.2085P. doi:10.1126 / science.282.5396.2085. PMID  9851930.
  114. ^ Korneev, K. V. (18 oktyabr 2019). "Sepsis va septik shokning sichqoncha modellari". Molekulyar biologiya. 53 (5): 704–717. doi:10.1134 / S0026893319050108. PMID  31661479. S2CID  204758015.
  115. ^ Lyuis AJ, Seymur CW va boshq. (Avgust 2016). "Sepsisning hozirgi murin modellari". Jarrohlik infektsiyalari. 17 (4): 385–93. doi:10.1089 / sur.2016.021. PMC  4960474. PMID  27305321.
  116. ^ Mills M, Estes MK (sentyabr 2016). "Yuqumli kasalliklar uchun fiziologik ahamiyatga ega bo'lgan inson to'qimalarining modellari". Bugungi kunda giyohvand moddalarni kashf etish. 21 (9): 1540–52. doi:10.1016 / j.drudis.2016.06.020. PMC  5365153. PMID  27352632.
  117. ^ Engber D (2013 yil 13-fevral). "Septic Shock". Slate. Arxivlandi asl nusxasidan 2017 yil 9 aprelda.
  118. ^ Seok J, Uorren HS va boshq. (2013 yil fevral). "Sichqoncha modellaridagi genomik reaktsiyalar insonning yallig'lanish kasalliklarini yomon taqlid qiladi". Amerika Qo'shma Shtatlari Milliy Fanlar Akademiyasi materiallari. 110 (9): 3507–12. Bibcode:2013PNAS..110.3507S. doi:10.1073 / pnas.1222878110. PMC  3587220. PMID  23401516.
  119. ^ Hazeldine J, Xempson P va boshq. (2016). "Katta travmatik va issiqlik shikastlanishlarida tizim biologiya tadqiqotlarining diagnostik va prognostik ahamiyati: sharh". Kuyishlar va travma. 4: 33. doi:10.1186 / s41038-016-0059-3. PMC  5030723. PMID  27672669.
  120. ^ a b Torio CM, Mur BJ (2006 yil 1-yanvar). "Milliy statsionar kasalxonasi xarajatlari: to'lovchining eng qimmat sharoitlari, 2013 yil". Sog'liqni saqlash xarajatlari va ulardan foydalanish loyihasi. Statistik qisqacha ma'lumot # 204. Sog'liqni saqlash tadqiqotlari va sifat agentligi, Milliy tibbiyot kutubxonasi. PMID  27359025. Arxivlandi asl nusxasidan 2017 yil 6 sentyabrda.
  121. ^ Pfuntner A, Wier LM va boshq. (2013 yil dekabr). "Qo'shma Shtatlarda kasalxonada qolish xarajatlari, 2011 yil". Sog'liqni saqlash xarajatlari va ulardan foydalanish loyihasi. 168-sonli statistik ma'lumot. Milliy tibbiyot kutubxonasi. PMID  24455786.
  122. ^ "Tarix". Omon qolish Sepsis kampaniyasi. Muhim tibbiyot tibbiyoti jamiyati. Arxivlandi asl nusxasidan 2014 yil 4 martda. Olingan 24 fevral 2014.
  123. ^ Sepsis alyansi. "Biz haqimizda". sepsis.org. Arxivlandi asl nusxasidan 2015 yil 8 sentyabrda. Olingan 8 oktyabr 2015.
  124. ^ Rozsa L, Apari P va boshq. (2017). "Sepsisning evolyutsion mantiqi". Infektsiya, genetika va evolyutsiya. 55: 135–41. doi:10.1016 / j.meegid.2017.09.006. PMID  28899789.

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