I-methylene blue nokuqonda ngemva kokuhlinzwa: izivivinyo kubantu nezindlela zokusebenza ezilwaneni

Ngezinye izikhathi abantu asebekhulile baphuma ekuhlinzweni okukhulu bengasakwazi ukucabanga ngokucacile njengangaphambili. Imindeni iyakubona lokhu. Ochwepheshe bezokwelapha bayakulinganisa. Umbuzo uwukuthi i-methylene blue, enikezwa ngesikhathi esiseduze nokubulawa kwezinzwa, iyabuvikela yini ubuchopho. Izinhlobo ezimbili zobufakazi ziphathelene nalowo mbuzo, futhi ziphendula izingxenye zawo ezihlukene. Isivivinyo kubantu esenziwa ngesikhathi esizungeze ukuhlinzwa sibika okwenzeka ezigulini. Imodeli yamagundane asekhulile iphakamisa ukuthi ukuvikelwa kungase kusebenze kanjani ngaphakathi kwamangqamuzana ezinzwa. Akukho kulokhu okuthatha indawo yokunye.

Isinyathelo sokuqala siwukwehlukanisa imiphumela emibili evame ukuhlanganiswa.

I-delirium nokwehla kokuqonda okulinganisiwe kuyimiqondo ehlukene

I-delirium yangemva kokuhlinzwa iwukuphazamiseka okusheshayo, okuguquguqukayo kokunaka nokuqaphela okwenzekayo. Isiguli sicabanga ngokucacile ngehora elithile bese sidideka kwelilandelayo. Izibhedlela ziyithola ngamathuluzi okuhlola asetshenziswa eceleni kombhede, njenge-3D-CAM, ngokuvamile izikhathi ezingaphezu kwesisodwa ngosuku, ngoba ukuhlola kanye kungase kungayiboni.

Ukuphazamiseka kwamakhono okuqonda ngemva kokuhlinzwa kuhlukile. Kuwukwehla okulinganisiwe ekuhlolweni okuhlelekile uma kuqhathaniswa nesilinganiso sokuqala sesiguli ngaphambi kokuhlinzwa, okuhlanganisa inkumbulo, ukunaka, namakhono okuhlela nokulawula imisebenzi. Ukuhlola kwenzeka ngemva kwezinsuku noma amasonto. Isiguli singaba nokukodwa ngaphandle kokunye.

Lo mehluko ubalulekile ngoba le miphumela emibili ilinganiswa ngamathuluzi ahlukene, ngezikhathi ezihlukene, nangabahloli abahlukene. Uma isivivinyo sibika kokubili, kufunde njengeziphetho ezimbili ezihlukene. Ulwazi oluyisisekelo ngale ndlela yokuqaphela lapho kufundwa imibhalo yezivivinyo luchazwe kokuthi indlela yokufunda ucwaningo nge-methylene blue.

Okwenziwa yisivivinyo kubantu

Ubufakazi obuyinhloko kubantu buvela esivivinyweni esivulekile esinokwabiwa ngokungahleliwe saseHuashan Hospital, esashicilelwa ku-Journal of Clinical Anesthesia ngo-2021. Sabhalisa iziguli ezingu-248 ezineminyaka engu-60 kuya ku-80 ezazihlinzwa ukuhlinzwa okukhulu okuhleliwe okungathinti inhliziyo futhi okwakungafaki ukuhlinzwa kwesimiso sezinzwa, okuhlanganisa ukuhlinzwa kwesifuba, kwamathambo, kwesimiso somchamo, nokukhulu kwesisu. Ingxenye yathola i-methylene blue engu-2 mg/kg emthanjeni, ihlanjululwe yaba ngu-50 mL futhi yafakwa phakathi kwemizuzu engu-60 ngokushesha ngemva kokuqala kokubulawa kwezinzwa. Enye ingxenye yathola u-50 mL wesisombululo sikasawoti ngesimiso sesikhathi esifanayo.

I-delirium yayiwumphumela oyinhloko owawuhlolwa. Abahloli basebenzisa i-3D-CAM kabili ngosuku, kuhlukaniswe okungenani amahora ayisithupha, ngezinsuku ezingu-1 kuya ku-5 ngemva kokuhlinzwa noma kuze kube yilapho isiguli siphuma esibhedlela, futhi bachaza okwatholwa ekuhlolweni okukhombisa i-delirium besebenzisa i-Memorial Delirium Assessment Scale. Ukudideka egumbini lokululama kwabhalwa ngokwehlukana njenge-delirium lapho kuvukwa ekubulaweni kwezinzwa. Ukuqonda kwakuwumphumela wesibili owawuhlolwa: uchungechunge lwezivivinyo ezihlelekile ngosuku olwandulela ukuhlinzwa futhi nangasezinsukwini ezingu-7 ngemva kokuhlinzwa, lapho ukwehla kwachazwa njengokubi kakhulu okwedlula ukuchezuka okujwayelekile okukodwa okungenani ezivivinyweni ezimbili. Lokho kuwukwehla kwesikhathi sokuqala, manje okuvame ukubizwa ngokuthi ukululama okulibazisekile kwamakhono okuqonda ahlobene nesimiso sezinzwa. Ezinyangeni ezintathu abacwaningi basebenzisa ukuhlola ngocingo, i-TICS-m, kodwa kwakungekho silinganiso sokuqala se-TICS-m sangaphambi kokuhlinzwa sokuqhathanisa.

Imiphumela yesikhathi sokuqala yayivuna i-methylene blue. I-delirium yavela ezigulini ezingu-9 kwezingu-124 ezathola i-methylene blue (amaphesenti angu-7.3) uma kuqhathaniswa nezingu-30 kwezingu-124 eqenjini lokuqhathanisa (amaphesenti angu-24.2), ngesilinganiso esilungisiwe sama-odds esingu-0.24 kanye nesikhawu sokuzethemba samaphesenti angu-95 esisuka ku-0.11 kuya ku-0.53. Ukwehla kokuqonda kwesikhathi sokuqala kwavela kwabangu-20 kwabangu-124 (amaphesenti angu-16.1) uma kuqhathaniswa nabangu-49 kwabangu-122 (amaphesenti angu-40.2). I-delirium lapho kuvukwa ekubulaweni kwezinzwa egumbini lokululama yayifana emaqenjini womabili, cishe amaphesenti angu-18 uma kuqhathaniswa nangu-23. Ezinyangeni ezintathu, amaphuzu okuhlolwa ngocingo ayecishe afane ngokuphelele (amanani aphakathi nendawo angu-34.5 no-34.0), kungekho mehluko obalulekile ngokwezibalo.

Lezo zinombolo zidinga ukubhekwa kanye nemikhawulo yazo. Isivivinyo sasichazwe ngokusobala njengesivulekile. Odokotela bokubulala izinzwa babazi ukuthi iziguli zabelwe liphi iqembu, futhi i-methylene blue yenza umchamo ube luhlaza okwesibhakabhaka oluxubene nokuluhlaza okotshani izinsuku ezintathu kuya kwezinhlanu, okungase kuvezele iziguli nabahloli ukuthi umuntu ukuliphi iqembu. Senziwa esikhungweni esisodwa. Ukulandelela ukuqonda okwakunokuhlolwa kwesilinganiso sokuqala okufanele kwathatha cishe isonto; ukuhlola ngocingo kwezinyanga ezintathu akukwazi ukukhombisa ushintsho kusukela esilinganisweni sokuqala ngoba awekho amaphuzu okuhlolwa ngocingo esilinganiso sokuqala. Izehlakalo ezafakwa emathebula, njengesicanucanu, ukuhlanza, nesiyezi, zazifana emaqenjini womabili, futhi akukho siguli okwabikwa ukuthi saba ne-serotonin syndrome noma i-anemia ebangelwa ukubhujiswa kwamangqamuzana abomvu egazi eyayibalulekile ngokwezokwelapha. Imfiva yayivame kakhulu nge-methylene blue (abangu-16 kwabangu-124 uma kuqhathaniswa nabangu-3 kwabangu-124). Ukusebenza kwesibindi okungajwayelekile kwavela emaqenjini womabili futhi kwahambisana nezigameko zokuhlinzwa kokususwa kwengxenye yesibindi.

Lokho okwengezwa yimodeli yamagundane asekhulile

Ucwaningo oluhlukile emagundaneni anezinyanga ezingu-18 ubudala lubuza umbuzo wendlela yokusebenza, hhayi owokwelapha abantu. Amagundane angamaduna angu-45 ohlobo lwe-C57BL/6J ahlukaniswa aba amaqembu amathathu anangu-15: athola umoya-mpilo kuphela, athola i-sevoflurane engamaphesenti angu-3 amahora amabili, noma athola i-sevoflurane efanayo ngemva kokujovwa kanye nge-methylene blue engu-5 mg/kg emgodini wesisu amahora amabili ngaphambi kwalokho. Ukufunda nenkumbulo kwahlolwa nge-Morris water maze, futhi izicubu ze-hippocampus zahlolwa ukuze kubhekwe ukuma kwama-mitochondria namaprotheni alawula ukuhlukana kwama-mitochondria.

I-sevoflurane yandisa i-protease SENP3, yasusa iprotheni encane eguqula amanye amaprotheni (SUMO2/3) ku-Drp1 elawula ukuhlukana, yenza ama-mitochondria ahlukane abe yizingcezu, futhi yenza ukusebenza ekuhlolweni ngomzila oyindida kube kubi. Ukunikezwa kwe-methylene blue kusengaphambili kwabuyisela emuva isinyathelo ngasinye salolo chungechunge: ukususwa okuncane kwe-SUMO ku-Drp1, ukuhlukana okuncane kube yizingcezu, namaphuzu enkumbulo angcono. Ababhali bethula isimo sokunamathiselwa kwe-SUMO ku-Drp1 njengeswishi exhumanisa ukuthola umuthi wokubulala izinzwa nokulimala kwama-mitochondria namakhono okuqonda.

Leyo yindlela yokusebenza ecacile, engahlolwa, futhi yenza umphumela obonwe kubantu ungamangazi kangako ngokwesayensi yezinto eziphilayo. Kodwa qaphela konke imodeli engakumeli. Lawa kwakungamagundane asekhulile kodwa ayephile kahle ngenye indlela, anikezwa ukubulawa kwezinzwa kuphela, ngaphandle kokuhlinzwa noma esinye isifo esikhona kanye nawo. Umuthi wajovwa emgodini wesisu amahora amabili ngaphambi kokuthola umuthi wokubulala izinzwa, okuyindlela yokunikeza umuthi kusengaphambili engafani nokufakwa kwawo emthanjeni ngemva kokuqala kokubulawa kwezinzwa esivivinyweni kubantu. Ubufakazi bezicubu ku-hippocampus yegundane abuqinisekisi ukuthi indlela efanayo yokusebenza ichaza umphumela kubantu.

Lezi zifundo ezimbili ziqhathaniswa

Uhlelo lwesivivinyo lwesibili, olukhudlwana, lucacisa ukuthi lo mkhakha uphokophelephi. Isivivinyo esibhalisiwe sokuhlinzwa kwamanyikwe i-NCT04529265 sahlela iziguli ezingu-314 ezineminyaka engu-55 kuya ku-80, ukufihlwa kokwabiwa kwamaqembu kubabambiqhaza nakubahloli bemiphumela, nemithamo emibili ngesikhathi sokuhlinzwa enesamba esingu-3 mg/kg, i-delirium ngesikhathi sokuhlala esibhedlela iwumphumela oyinhloko, kanti ukuqonda ngosuku lwesi-7, izinkomba zokuvuvukala, nokulandelela okuhlobene nomdlavuza isikhathi eside kuyimiphumela yesibili. Irekhodi lokubhaliswa likhombisa ukuqedwa ngoDisemba 2024, futhi imiphumela isishicilelwe ku-Journal of Clinical Anesthesia ngo-2026. Lokho kuphindwa kwesivivinyo ngokufihlwa kokwabiwa kwamaqembu yisifundo okufanele sibhekwe ngaphambi kokuthatha okwatholwa esivivinyweni esivulekile njengokufakazelwe ngokuphelele.

Ukuphepha egumbini lokuhlinza akudluliseli ekusetshenzisweni ekhaya

Yonke imiphumela yokuqonda engenhla ivela ekusetshenzisweni ngokufakwa emthanjeni okuqondiswa ochwepheshe ngesikhathi sokuhlinzwa. Leso simo sihlanganisa odokotela bokubulala izinzwa, amadivayisi okuqapha, imithi yokuvuselela isiguli, nokuhlola imithi engase ihlangane nayo. Akukho kulokhu okudlulisela ekuyithatheni ngomlomo ekhaya.

Kunezixwayiso ezimbili eziqondile. I-methylene blue ivimbela i-monoamine oxidase, ngakho ukuyihlanganisa nemithi yokucindezeleka kwengqondo esebenza ku-serotonin kungabangela i-serotonin syndrome, ingozi ulwazi lokunquma umuthi ojovwayo oluyiveza njengesixwayiso esisebhokisini; imithi ehlangana nayo ichazwe kokuthi ukuhlangana kwe-methylene blue neminye imithi. Iziguli ezinokuntuleka kwe-G6PD zisengozini yokubhujiswa kwamangqamuzana abomvu egazi. Ukuphenduka komchamo nesikhumba kube luhlaza okwesibhakabhaka, okungenabungozi ngokwakho, nakho kuyisizathu sokuthi izivivinyo zesikhathi esizayo kudingeke zenze okwengeziwe ekufihleni ukwabiwa kwamaqembu kunalokho okwenziwa yisivivinyo esivulekile. Izimiso ezijwayelekile zokuphepha ekuphatheni nasekutholeni umkhiqizo zifingqiwe kokuthi izisekelo zokuphepha kwe-methylene blue.

Isiphetho

Isivivinyo esisodwa esivulekile ezigulini ezikhulile ezihlinzwayo sibika i-delirium encane kakhulu nokwehla okuncane okulinganisiwe esikhathini sokuqala ngemva komthamo owodwa we-IV ngesikhathi sokuhlinzwa, kungekho mehluko wokuqonda ezinyangeni ezintathu futhi kukhona nobuthakathaka bokufihlwa kokwabiwa kwamaqembu obudalulwa ngababhali baso uqobo. Imodeli yokubulawa kwezinzwa emagundaneni asekhulile inikeza incazelo ehambisanayo yama-mitochondria yokuthi ukuvikelwa okunjalo kungase kwenzeke kanjani. Kuthathe lokho njengezitatimende ezimbili ezihlukene: umphumela obonwe kubantu osalinde ukuphindwa ngokufihlwa kokwabiwa kwamaqembu, nendlela yokusebenza esalinde ukuqinisekiswa kubantu. Abafundi abalandela imiphumela yenkumbulo ekugugeni ngokubanzi bangase futhi bathande ukufunda i-methylene blue nenkumbulo ekugugeni.