Isihloko
I-methylene blue ye-vasoplegia nokushaqeka kwe-sepsis: lokho okuboniswa yizivivinyo zomtholampilo
Isiguli siphuma egumbini lokuhlinzela ngemva kokuhlinzwa kwenhliziyo, nenhliziyo yaso ikhipha igazi ngenani elivamile kodwa umfutho wegazi ungakwazi ukuhlala uzinzile. Komunye umbhede, isiguli esinokutheleleka okukhulu sidinga imithamo ye-norepinephrine elokhu ikhula ukuze umfutho uhlale ungaphezu kwezinga elihlosiwe. Kuzo zombili lezi zimo, imithambo ilahlekelwe ukuqina kwayo, futhi zombili zenze odokotela bokunakekelwa okujulile bazame i-methylene blue. Le ndatshana ibuyekeza lokho izivivinyo zomtholampilo ezakuhlola ngempela nalokho ezakuthola.
Ukwehlukanisa izinto ezimbili kusiza ukuhlela konke okulandelayo. Okokuqala, i-vasoplegia ngemva kokuhlinzwa kwenhliziyo nokushaqeka kwe-sepsis kuyizifo ezihlukene, ezihlolwa ngezivivinyo eziklanywe ngezindlela ezihlukene, ngakho ngasinye sinesigaba saso. Okwesibili, ukudinga imithi emincane enyusa umfutho wegazi akufani nokwanda kwamathuba okusinda. Izivivinyo eziningi zalinganisa okokuqala; cishe azikho ezazinkulu ngokwanele ukuphendula umbuzo wesibili.
Kungani i-methylene blue ingase iqinise imithambo
Imithambo yegazi ethwala igazi lisuka enhliziyweni iyancipha futhi inwebe njengoba imisipha yayo ebushelelezi ifinyela futhi ixega, futhi ububanzi bayo bunquma ingxenye enkulu yokumelana kwemithambo yomzimba nokugeleza kwegazi. Olunye uphawu olwenza imisipha ixege lusuka ku-nitric oxide, ludlule ku-guanylate cyclase encibilikayo, luye ku-cyclic GMP, ekhuthaza ukuxega. I-methylene blue iphazamisa le ndlela, yingakho ingamelana nokunwebeka okukhulu kwemithambo okwenzeka ngesikhathi sokushaqeka. Indlela umuthi osebenza ngayo ibanzi kunokuvimba into eyodwa kuphela: ocwaningweni lokuhlola ukwakheka kwe-nitric oxide nokuxega kwemithambo, i-methylene blue yasebenza ezindaweni ezingaphezu kweyodwa ochungechungeni lokudluliswa kwezimpawu. Lolo cwaningo luchaza indlela yokusebenza engaba khona. Alubikezeli ukuthi umfutho wegazi wesiguli esithile uzophendula kanjani.
Zonke izivivinyo ezingezansi zasebenzisa i-methylene blue efakwa emthanjeni esibhedlela, ngaphezu kokunakekelwa okujulile okujwayelekile. Akukho lapha okuhlola umkhiqizo ophuzwa ngomlomo ekhaya.
I-vasoplegia ngemva kokuhlinzwa kwenhliziyo
Lapha i-vasoplegia isho ukuncipha okukhulu kokuqina kwemithambo ngemva kokusetshenziswa komshini odlulisa igazi ngaphandle kwenhliziyo namaphaphu: umfutho ophansi nokumelana okuphansi, yize inani legazi elikhishwa yinhliziyo lisagcinwe. Ubufakazi obuvela ezivivinyweni ezabela iziguli emaqenjini ngokungahleliwe zokwelapha i-vasoplegia esivele ikhona buncike kakhulu esivivinyweni esisodwa esincane. Izivivinyo ezimbili ezengeziwe zahlola i-methylene blue ngaphambi noma ngesikhathi sokuhlinzwa ukuze kuvinjelwe i-vasoplegia, okuwumbuzo ohlukile womtholampilo.
Esivivinyweni sikaLevin nozakwabo esabela iziguli ngokungahleliwe, esahlola i-vasoplegia esivele ikhona ngemva kokuhlinzwa, iziguli ezingu-56 zabelwa ukuthola u-1.5 mg/kg ofakwa emthanjeni ngehora elilodwa noma i-placebo. I-vasoplegia yaphela ngokushesha eqenjini elathola umuthi, kuyilapho iziguli ezingu-8 kwezingu-28 ezathola i-placebo zaqhubeka zine-vasoplegia ngaphezu kwamahora angu-48, futhi ukufa kwaba ngu-0 kwezingu-28 uma kuqhathaniswa no-6 kwezingu-28. Umphumela wokuhlehlisa ukushaqeka uyaphawuleka, kodwa iziguli ezingu-56 azikwazi ukuqinisekisa umthelela ekusindeni, futhi umehluko wokufa awuqinile ngokwanele ukuba usetshenziswe njengesisekelo sesiphetho esibanzi.
Izivivinyo zokuvimbela azikhombi ohlangothini olulodwa. Ocwaningweni lukaOzal nozakwabo lweziguli ezisengozini enkulu ezihlinzwa ukuze kudalwe indlela entsha yegazi emithanjeni yenhliziyo, ukufakwa komuthi emthanjeni ngaphambi kokuhlinzwa kwanciphisa i-vasoplegia isuka ku-13 kwezingu-50 yaya ku-0 kwezingu-50. UMaslow nozakwabo bathola umphumela owahlala isikhathi esifushane phakathi nokuhlinzwa kusetshenziswa umshini odlulisa igazi ngaphandle kwenhliziyo namaphaphu, kanti uCho nozakwabo bathola ukuthi cishe kwakungekho nzuzo ekugelezeni kwegazi noma ekunciphiseni imithi enyusa umfutho wegazi. Ukuvimbela ezigulini ezikhethiwe ezihlinzwayo nokwelapha ngokuphuthumayo i-vasoplegia esivele ikhona kufanele kuthathwe njengeziphetho ezihlukene ezisekelwe ebufakazini obuhlukene.
Ukushaqeka kwe-sepsis
Ukushaqeka kwe-sepsis kuhlanganisa ukutheleleka nokwehluleka kokujikeleza kwegazi okuqhubekayo ngemva kokunikezwa koketshezi. Ngakho i-norepinephrine iba yinsika yokunakekelwa, futhi izivivinyo zibuza ukuthi i-methylene blue iyasinciphisa yini isikhathi sokusebenzisa ama-catecholamine. Izimpawu zemiphumela zivumelana kakhulu kunasekuhlinzweni, kodwa zisahlukahlukene, futhi zimayelana nokunciphisa imithi enyusa umfutho wegazi kunokusinda.
Isivivinyo esikhulu kunazo zonke sakamuva ucwaningo lukaIbarra-Estrada nozakwabo lwango-2023, olwabela iziguli ngokungahleliwe ukuze kuhlolwe i-methylene blue eyengezwa kusenesikhathi ekwelashweni. Kulo, abantu abadala abangu-91 abafakwa ekuhlaziyweni bathola umuthi ofakwa emthanjeni amahora ayisithupha ngosuku, imithamo emithathu, noma i-placebo efana nawo, ngaphezu kwe-norepinephrine, i-hydrocortisone, ne-vasopressin lapho kudingeka. Isikhathi esimaphakathi ngokwe-median kuze kuyekwe imithi enyusa umfutho wegazi sasingamahora angu-69 uma kuqhathaniswa namahora angu-94, kuyilapho ukufa nesikhathi sokusebenzisa umshini osiza ukuphefumula kwakufana. Izivivinyo zangaphambili zazincane: isivivinyo sokuqala sikaKirov nozakwabo seziguli ezingu-20 sabonisa ukuncipha okukhulu kwama-catecholamine ngemva komthamo osheshayo ongu-2 mg/kg, owalandelwa ukufakwa kwemithamo ekhuphukayo emthanjeni. UMemis nozakwabo bathola umfutho wegazi omaphakathi emithanjeni ophakeme ngemva kokufakwa komuthi (85 uma kuqhathaniswa no-74 mmHg), ngaphandle kwesilinganiso somphumela sokuncipha kwemithi enyusa umfutho wegazi. Ngokuphambene nalokhu, isivivinyo sikaDong nozakwabo seziguli ezingu-72, esasebenzisa i-placebo njengesiqhathaniso, asitholanga nzuzo ebalulekile ku-norepinephrine noma kumfutho wegazi. Okunye ukuqhathanisa kwathola ukuthi i-vasopressin yayingcono kune-methylene blue njengomuthi wesibili onyusa umfutho wegazi emahoreni angu-12 nangu-24. Ucwaningo lokuthola umthamo olwenziwa nguJuffermans nozakwabo lwabonisa ukuthi umfutho nokumelana kwemithambo kwakukhuphuka njengoba umthamo ukhuphuka, kodwa ukuncipha kokugeleza kwegazi ezithweni zesisu kwaba yinto ekhathazayo ku-7 mg/kg.
Ithebula lezivivinyo
U-IV usho ukufakwa emthanjeni. U-NE usho i-norepinephrine. U-MAP usho umfutho wegazi omaphakathi emithanjeni. U-SVR usho ukumelana kwemithambo yomzimba nokugeleza kwegazi. Umugqa ngamunye uchaza indlela umuthi owasetshenziswa ngayo ocwaningweni, hhayi isincomo sokwelashwa.
| Isivivinyo nesimo | Indlela yokunikeza umuthi | Umphumela emithini enyusa umfutho wegazi | Umphumela ekugelezeni kwegazi | Ukufa | Izehlakalo ezingezinhle |
|---|---|---|---|---|---|
| Levin 2004: i-vasoplegia esivele ikhona ngemva kokuhlinzwa kwenhliziyo, 28 uma kuqhathaniswa no-28 | 1.5 mg/kg IV phakathi nehora elingu-1 | I-vasoplegia yaphela kuzo zonke iziguli ezathola umuthi phakathi kwamahora angu-6; abangu-8 kwabangu-28 beqembu lokuqhathanisa babesathintekile ngemva kwamahora angu-48 | U-MAP no-SVR babuyela ngokushesha eqenjini elathola umuthi | 0 kwabangu-28 uma kuqhathaniswa no-6 kwabangu-28; sincane kakhulu ukuqinisekisa umthelela ekusindeni | Akubikwanga uphawu lobuthi obukhulu ngale ndlela yokunikeza umuthi |
| Ozal 2005: ukuvimbela ezigulini ezingu-100 ezisengozini enkulu ezihlinzwa ukuze kudalwe indlela entsha yegazi emithanjeni yenhliziyo, 50 uma kuqhathaniswa no-50 | Isixazululo esingamaphesenti angu-1 safakwa emthanjeni kusukela ehoreni elingu-1 ngaphambi kokuhlinzwa | I-vasoplegia ku-0 kwabangu-50 uma kuqhathaniswa no-13 kwabangu-50; ukuvimbela, hhayi ukwelapha ngokuphuthumayo | Imifutho yegazi yayiphakeme eqenjini elathola umuthi ngesikhathi sokuhlinzwa | Akusona isivivinyo sokufa | Akubikwanga uphawu lobuthi obukhulu |
| Cho: i-methylene blue yokuvimbela ekuhlinzweni kwenhliziyo | Ukufakwa emthanjeni ngesikhathi esizungeze ukuhlinzwa | Awukho umehluko ophawulekayo emithini enyusa umfutho wegazi | U-MAP no-SVR babengahlukile ngendlela ephawulekayo | Akusona isivivinyo sokufa | Akubikwanga izinga eliqondene ngqo nezehlakalo ezingezinhle |
| Kirov 2001: isivivinyo sokuqala sokushaqeka kwe-sepsis, 10 uma kuqhathaniswa no-10 | Umthamo osheshayo ongu-2 mg/kg, bese kufakwa umuthi emthanjeni ngezinyathelo kuze kube ngu-5.75 mg/kg usuwonke | U-NE wehla kuze kufike kumaphesenti angu-87; i-epinephrine yehla ngamaphesenti angu-81; i-dopamine yehla ngamaphesenti angu-40 | U-MAP wayephakeme ngokuphawulekayo emahoreni angu-6 nangu-24 | Ukufa ezinsukwini ezingu-28: 5 kwabangu-10 uma kuqhathaniswa no-7 kwabangu-10; akusona isivivinyo sokufa | Umchamo oluhlaza okwesibhakabhaka nokushintsha kombala wesikhumba; alukho uphawu lobuthi obukhulu ezithweni |
| Memis 2002: i-sepsis enzima, 15 uma kuqhathaniswa no-15 | 0.5 mg/kg ngehora amahora angu-6 | Akukho silinganiso somphumela esinikeza inani lokuncipha kwemithi | U-MAP ngemva kokufakwa komuthi: 85 uma kuqhathaniswa no-74 mmHg | Asizange sibe namandla ezibalo anele ukuhlola ukufa | Akubikwanga uphawu lobuthi obukhulu |
| Ibarra-Estrada 2023: ukushaqeka kwe-sepsis, 91 bahlaziywa | Ukufakwa emthanjeni amahora ayisithupha ngosuku, imithamo emithathu | Isikhathi esimaphakathi ngokwe-median kuze kuyekwe imithi enyusa umfutho wegazi: 69 uma kuqhathaniswa namahora angu-94 | Imifutho yegazi yalawulwa ukuze ifinyelele emazingeni ahlosiwe kuwo womabili amaqembu | Ukufa kwakufana phakathi kwamaqembu | Umchamo oluhlaza okwesibhakabhaka noma oluhlaza njengotshani wawuvamile; abantu abashoda nge-G6PD nababesanda kusebenzisa ama-SSRI abazange bafakwe |
| Dong 2025: ukushaqeka kwe-sepsis ezigulini ezisemshinini osiza ukuphefumula, 36 uma kuqhathaniswa no-36 | 2 mg/kg phakathi kwemizuzu engu-15 kanye no-1 mg/kg phakathi kwamahora angu-12 | Umehluko ku-NE wawusondele kuziro; awukho umehluko esikhathini kuze kuyekwe imithi enyusa umfutho wegazi | Umehluko ku-MAP wawungu-1.2 mmHg ngaphansi, ungaphawuleki ngokwezibalo; ukugeleza emithanjeni emincane kwathuthuka | Ukufa ezinsukwini ezingu-28: 9 kwabangu-36 uma kuqhathaniswa no-15 kwabangu-36, akuphawuleki ngokwezibalo | Umchamo oluhlaza okwesibhakabhaka noma oluhlaza njengotshani kuzo zonke iziguli ezathola umuthi; alukho uphawu lomphumela omubi esibindini, ezinso, noma ekutholeni umoya-mpilo |
Ingabe lokhu kubonisa ukufa okumbalwa?
Ukuhlaziywa okuhlanganisa izivivinyo kuye kwabonakala kunemiphumela engcono kunezivivinyo ngazinye, kodwa izilinganiso ezinhle ziba buthaka uma zihlolisiswa. Ukuhlanganiswa kwezivivinyo eziyisithupha zokushaqeka kwe-sepsis kwango-2024 kwathola isilinganiso sobungozi bokufa esikhathini esifushane esingu-0.66, kodwa umphumela awusabanga ophawulekayo ngokwezibalo lapho kususwa izivivinyo ezazinobungozi obukhulu bokuchema. Ukuhlanganiswa kwakamuva kakhulu kwezivivinyo ezilawulwayo ezabela iziguli ngokungahleliwe kuphela, okuhlanganisa izivivinyo eziyisishiyagalolunye neziguli ezingu-535, kwathola isilinganiso se-odds sokufa ezinsukwini ezingu-28 kuya kwezingu-30 esingu-0.73, nesikhawu sokuthembeka esisuka ku-0.40 kuya ku-1.36, esingaphawuleki ngokwezibalo. Ukuhlaziywa kwaso kokulandelana kwezivivinyo kwalinganisela ukuthi kwakuzodingeka iziguli ezingu-1,773, uma kuqhathaniswa namakhulu ambalwa ayetholakala. Isifinyezo esithembekile sithi inzuzo ekusindeni ayikaqinisekiswa, hhayi ukuthi kuqinisekisiwe ukuthi ayikho.
Amanothi okuphepha avela ebufakazini basesibhedlela
Imiphumela evamile ezivivinyweni kwakuwumchamo oluhlaza okwesibhakabhaka noma oluhlaza njengotshani nokushintsha kombala wesikhumba, kanye nokwenyuka okuncane kwe-methemoglobin. Izingozi ezinkulu zivela emininingwaneni yomkhiqizo onelayisensi ofakwa emthanjeni, kunasezibalweni zezehlakalo zezivivinyo: i-serotonin syndrome lapho uhlanganiswa nemithi ethinta i-serotonin noma ama-opioid; ukungavunyelwa kokusetshenziswa kwabashoda nge-G6PD ngenxa yengozi yokubhidlika kwamangqamuzana abomvu egazi; ukufundwa okuphansi okungamanga kwe-pulse oximeter ngesikhathi nangemva nje kokufakwa emthanjeni; kanye nomfutho wegazi ophakeme njengomphumela omubi obikiwe. Izivivinyo eziningana zakamuva azizange zifake iziguli ezishoda nge-G6PD noma ezazisanda kusebenzisa imithi ethinta i-serotonin, ngakho amathebula azo okuphepha angenazo izinkinga ezinkulu awalinganisi ubungozi kulawo maqembu. Lobu bufakazi kufanele futhi bufundwe kanye nokubuka kabanzi ukusetshenziswa emtholampilo kanye nokuhlolwa kokuphepha; abafundi abangajwayele indlela izivivinyo eziklanywa ngayo bangaqala ngomhlahlandlela wokufunda ucwaningo lwe-methylene blue.
I-vasoplegia nokushaqeka kwe-sepsis kungase kudinge ukubuyekezwa okujulile okuhlukene uma ubufakazi bukhula, kodwa imibhalo yocwaningo ekhona manje ihambisana nokubuyekezwa okukodwa kokunakekelwa okujulile: umphumela wangempela wokunciphisa ububanzi bemithambo nokunciphisa isidingo semithi enyusa umfutho wegazi, obonakala ngokucace kakhulu ku-vasoplegia esivele ikhona nasekuqaleni kokushaqeka kwe-sepsis, ngaphandle kwenzuzo yokusinda esibonisiwe, futhi kunemingcele yokuphepha eshiya ngaphandle amaqembu amaningana eziguli. Noma ubani obhekene nalezi zimo usevele esekunakekelweni okujulile, futhi ukusetshenziswa kwe-methylene blue kulesi simo kuyisinqumo segumbi lokunakekelwa okujulile (ICU) esenziwa yithimba elilaphayo, hhayi ukwelashwa kwasekhaya okucatshangwa ngokususelwa ekufakweni komuthi emthanjeni esibhedlela.