Methylene blue ndi luso la kuganiza pambuyo pa opaleshoni: mayesero mwa anthu ndi njira zogwirira ntchito mwa nyama

Anthu achikulire nthawi zina amatuluka mu opaleshoni yayikulu ali ndi vuto loganiza bwino kuposa momwe ankachitira kale. Achibale amaona zimenezi. Akatswiri a zachipatala amaziyeza. Funso n’lakuti kaya methylene blue, ikaperekedwa pa nthawi yopereka mankhwala ogonetsa, imateteza ubongo. Pali mitundu iwiri ya umboni yokhudza funsoli, ndipo imayankha mbali zake zosiyana. Mayesero mwa anthu pa nthawi yozungulira opaleshoni amafotokoza zimene zinachitikira odwala. Kafukufuku wa mbewa zokalamba amapereka lingaliro la mmene chitetezo chingagwirire ntchito m’maselo a mitsempha. Palibe umboni umodzi umene ungalowe m’malo mwa winawo.

Choyamba ndi kusiyanitsa zotsatira ziwiri zimene nthawi zambiri zimaphatikizidwa ngati kuti ndi chinthu chimodzi.

Delirium ndi kutsika koyezedwa kwa luso la kuganiza ndi zinthu zosiyana

Delirium pambuyo pa opaleshoni ndi kusokonezeka mwadzidzidzi kwa chidwi ndi kuzindikira zimene zikuchitika, komwe kumasintha nthawi ndi nthawi. Wodwala angakhale akuganiza bwinobwino ola limodzi, kenako n’kusokonezeka ola lotsatira. Zipatala zimazindikira vutoli pogwiritsa ntchito zida zoyezera pafupi ndi bedi, monga 3D-CAM, nthawi zambiri kuposa kamodzi patsiku, chifukwa kuliyesa kamodzi kokha kungalephere kulipeza.

Kusagwira bwino ntchito kwa luso la kuganiza pambuyo pa opaleshoni ndi chinthu china. Ndi kutsika koyezedwa ndi mayeso okhazikika poyerekezera ndi mmene wodwalayo analili asanachitidwe opaleshoni, kuphatikizapo kukumbukira, chidwi, ndi luso lokonza ndi kuwongolera zochita. Mayesowa amachitika patapita masiku kapena milungu. Wodwala angakhale ndi vuto limodzi popanda linzake.

Kusiyanitsa kumeneku n’kofunika chifukwa zotsatira ziwirizi zimayesedwa ndi zida zosiyana, pa nthawi zosiyana, ndiponso ndi oyesa osiyana. Mayesero akafotokoza zonsezi, ziwerengeni ngati zonena ziwiri zosiyana. Mfundo zoyambira za njira imeneyi yowerengera zolemba za mayesero zafotokozedwa mu mmene mungawerengere kafukufuku wa methylene blue.

Zimene mayesero mwa anthu anachita

Umboni waukulu mwa anthu umachokera ku mayesero ogawa anthu mwachisawawa osabisa magulu ku Huashan Hospital, omwe anafalitsidwa mu Journal of Clinical Anesthesia mu 2021. Analowetsa odwala 248 a zaka 60 mpaka 80 amene anali kuchitidwa opaleshoni yayikulu yokonzedweratu yosakhudza mtima, komanso yosaphatikizapo opaleshoni ya ubongo kapena mitsempha. Opaleshonizi zinaphatikizapo za m’chifuwa, mafupa, njira ya mkodzo, ndi zazikulu za m’mimba. Theka linalandira methylene blue 2 mg/kg mumtsempha, yosungunulidwa kufika pa 50 mL ndipo yolowetsedwa pang’onopang’ono mkati mwa mphindi 60 atangoyamba kugonetsedwa ndi mankhwala. Theka linalandira 50 mL ya madzi amchere pa nthawi yomweyo.

Delirium inali zotsatira zazikulu zoyezedwa. Oyesa anafufuza pogwiritsa ntchito 3D-CAM kawiri patsiku, ndi kusiyana kwa maola osachepera asanu ndi limodzi, kuyambira tsiku 1 mpaka 5 pambuyo pa opaleshoni kapena mpaka wodwalayo atatulutsidwa m’chipatala. Amene anapezeka ndi vutoli anayezedwanso ndi Memorial Delirium Assessment Scale kuti afotokoze mmene vutolo linalili. Kusokonezeka m’chipinda chodzutsiramo odwala kunalembedwa padera ngati delirium ya podzuka ku mankhwala ogonetsa. Luso la kuganiza linali zotsatira zachiwiri zoyezedwa: mayeso angapo okhazikika anachitika tsiku limodzi opaleshoni isanachitike ndiponso pafupifupi tsiku 7 pambuyo pa opaleshoni. Kutsika kunatanthauzidwa ngati kuipa koposa muyezo umodzi wa kupatuka kokhazikika pa mayeso osachepera awiri. Uku ndi kutsika koyambirira, komwe masiku ano nthawi zambiri kumatchedwa kuchedwa kubwerera kwa luso la ubongo ndi kuganiza. Pa miyezi itatu, ofufuza anagwiritsa ntchito kuyesa kudzera pa telefoni, TICS-m, koma panalibe zotsatira za TICS-m za opaleshoni isanachitike zoti ayerekezere nazo.

Zotsatira zoyambirira zinakomera methylene blue. Delirium inachitika mwa odwala 9 mwa 124 amene analandira methylene blue (7.3 peresenti), poyerekezera ndi 30 mwa 124 a gulu loyerekezera (24.2 peresenti). Chiŵerengero cha mwayi chochitikira vutoli, chitakonzedwa kuti chiwerengere zinthu zina, chinali 0.24, ndi malire odalirika a 95 peresenti kuyambira 0.11 mpaka 0.53. Kutsika koyambirira kwa luso la kuganiza kunachitika mwa 20 mwa 124 (16.1 peresenti), poyerekezera ndi 49 mwa 122 (40.2 peresenti). Delirium ya podzuka m’chipinda chodzutsiramo odwala inali yofanana pakati pa maguluwo, pafupifupi 18 poyerekezera ndi 23 peresenti. Pa miyezi itatu, zotsatira za kuyesa pa telefoni zinali pafupifupi zofanana (ziŵerengero zapakati 34.5 ndi 34.0), popanda kusiyana kotsimikizika mwa ziŵerengero.

Ziŵerengerozi ziyenera kuwerengedwa limodzi ndi zofooka zake. Mayeserowa ananenedwa momveka bwino kuti sanabise magulu. Madokotala opereka mankhwala ogonetsa ankadziwa gulu la wodwala aliyense, ndipo methylene blue imasandutsa mkodzo kukhala wabuluu wobiriwira kwa masiku atatu mpaka asanu, zimene zingathandize odwala ndi oyesa kudziwa gululo. Mayeserowa anachitikira pamalo amodzi. Kutsatira luso la kuganiza pogwiritsa ntchito mayeso oyenera a poyambira kunatenga pafupifupi mlungu umodzi; kuyesa pa telefoni pa miyezi itatu sikungasonyeze kusintha kuchokera poyambira chifukwa panalibe zotsatira za kuyesa koyambirira pa telefoni. Zochitika zolembedwa m’matebulo monga nseru, kusanza, ndi chizungulire zinali zofanana pakati pa maguluwo, ndipo panalibe wodwala amene ananenedwa kukhala ndi vuto la serotonin kapena kuchepa kwa magazi chifukwa cha kuwonongeka kwa maselo ofiira komwe kunali kofunika pachipatala. Kutentha thupi kunali kofala kwambiri mwa amene analandira methylene blue (16 mwa 124 poyerekezera ndi 3 mwa 124). Kusagwira bwino ntchito kwa chiwindi kunaonekera m’magulu onse ndipo kunkagwirizana ndi odwala amene anachotsedwa mbali ya chiwindi.

Zimene kafukufuku wa mbewa zokalamba akuwonjezera

Kafukufuku wina mwa mbewa za miyezi 18 amafunsa za njira yogwirira ntchito, osati zotsatira mwa odwala. Mbewa zamphongo 45 za mtundu wa C57BL/6J zinagawidwa m’magulu atatu a mbewa khumi ndi zisanu: gulu lolandira oxygen yokha, gulu lolandira sevoflurane ya 3 peresenti kwa maola awiri, kapena gulu lolandira sevoflurane yomweyi koma litabayidwa kamodzi methylene blue 5 mg/kg m’bowo la m’mimba maola awiri m’mbuyomo. Kuphunzira ndi kukumbukira zinayesedwa pogwiritsa ntchito mayeso a Morris a njira zosokoneza za m’madzi. Minofu ya hippocampus inaunikidwa kuti aone mawonekedwe a mitochondria ndi mapuloteni amene amayang’anira kugawikana kwa mitochondria.

Sevoflurane inachulukitsa enzyme yodula mapuloteni yotchedwa SENP3, inachotsa puloteni yaing’ono yosintha mapuloteni ena (SUMO2/3) pa Drp1 yomwe imayang’anira kugawikana, inagawa mitochondria m’tizidutswa, ndipo inachititsa kuti mbewa zichite moyipa pa mayeso a njira zosokoneza. Kupereka methylene blue pasadakhale kunabwezeretsa mbali iliyonse ya unyolo umenewu: kuchotsa SUMO pa Drp1 kunachepa, kugawikana m’tizidutswa kunachepa, ndipo zotsatira za kukumbukira zinakhala bwino. Olembawo amafotokoza mmene SUMO imalumikizidwira pa Drp1 ngati chosinthira chimene chimagwirizanitsa kulandira mankhwala ogonetsa ndi kuwonongeka kwa mitochondria ndi luso la kuganiza.

Imeneyi ndi njira yeniyeni imene ingayesedwe, ndipo imathandiza kuti zotsatira zoyambirira mwa anthu zikhale zosadabwitsa kwambiri poyang’ana mmene thupi limagwirira ntchito. Koma ganizirani zinthu zonse zimene kafukufukuyu sakuyimira. Izi zinali mbewa zokalamba koma zathanzi m’njira zina, zopatsidwa mankhwala ogonetsa okha, popanda opaleshoni kapena matenda ena. Mankhwalawo anabayidwa m’mimba maola awiri asanapatsidwe mankhwala ogonetsa, njira yopereka chithandizo pasadakhale yosiyana ndi kulowetsa mankhwala mumtsempha pambuyo poyamba kugonetsa pa opaleshoni. Umboni wa m’minofu ya hippocampus ya mbewa sutsimikizira kuti njira yomweyi ndiyo ikufotokoza zotsatira mwa anthu.

Kafukufuku awiriwa akayerekezana

Ndondomeko yachiwiri, yayikulu kwambiri, imamveketsa kumene kafukufuku wa nkhaniyi akulowera. Mayesero olembetsedwa a opaleshoni ya kapamba NCT04529265 anakonza zophatikiza odwala 314 a zaka 55 mpaka 80, kubisa magulu kwa otenga nawo mbali ndi oyesa zotsatira, ndiponso kupereka mankhwala kawiri mkati mwa opaleshoni, okwana 3 mg/kg. Delirium pa nthawi yogonekedwa m’chipatala inali zotsatira zazikulu zoyezedwa, ndipo luso la kuganiza pa tsiku 7, zizindikiro za kutupa m’thupi, ndi kutsatira zotsatira zokhudza khansa kwa nthawi yaitali zinali zotsatira zachiwiri. Zolemba za m’kaundula zikusonyeza kuti mayeserowa anamalizidwa mu December 2024, ndipo zotsatira zake zinafalitsidwa pambuyo pake mu Journal of Clinical Anesthesia mu 2026. Mayesero obwerezawa obisa magulu ndi amene ayenera kutsatiridwa musanasandutse zomwe zinapezeka m’mayesero osabisa magulu kukhala mfundo yotsimikizika.

Chitetezo cha m’chipinda cha opaleshoni sichimangopitirirabe kunyumba

Zotsatira zonse zokhudza luso la kuganiza zomwe zatchulidwa pamwambapa zinachokera ku kugwiritsa ntchito mankhwala mumtsempha moyang’aniridwa pa nthawi ya opaleshoni. Malo amenewo ali ndi madokotala opereka mankhwala ogonetsa, zida zoyang’anira wodwala, mankhwala otsitsimutsa, ndi kufufuza mankhwala ena amene angachite zinthu limodzi ndi mankhwalawa. Zimenezi sizigwiranso ntchito mofanana pa kumwa mankhwala kunyumba.

Pali machenjezo awiri apadera. Methylene blue imaletsa kugwira ntchito kwa monoamine oxidase, choncho kuiphatikiza ndi mankhwala ochepetsa kukhumudwa amene amakhudza serotonin kungayambitse vuto la serotonin. Malangizo operekera mankhwala obayidwa ali ndi chenjezo la m’bokosi lokhudza chiopsezochi; mankhwala amene angachite zinthu limodzi nawo afotokozedwa mu kugwirizana kwa methylene blue ndi mankhwala ena. Odwala amene ali ndi kuchepa kwa G6PD ali pachiopsezo cha kuwonongeka kwa maselo ofiira a magazi. Kusanduka kwabuluu kwa mkodzo ndi khungu, komwe pakokha sikuvulaza, ndi chifukwa chinanso chimene mayesero amtsogolo ayenera kuyesetsa kwambiri kubisa magulu kuposa momwe mayesero osabisa magulu anachitira. Mfundo zazikulu za chitetezo posamalira ndi kupeza mankhwalawa zafotokozedwa mwachidule mu mfundo zoyambira za chitetezo cha methylene blue.

Mfundo yomaliza

Mayesero amodzi osabisa magulu mwa odwala achikulire ochitidwa opaleshoni akusonyeza kuchepa kwakukulu kwa delirium ndi kutsika koyambirira kwa luso la kuganiza loyezedwa pambuyo popereka methylene blue kamodzi mumtsempha mkati mwa opaleshoni. Sanapeze kusiyana kwa luso la kuganiza pa miyezi itatu, ndipo olembawo anafotokoza okha zofooka zokhudza kubisa magulu. Kafukufuku wa mankhwala ogonetsa mwa mbewa zokalamba amapereka kufotokoza kogwirizana kokhudza mitochondria kwa mmene chitetezo choterocho chingachitikire. Onani zimenezi ngati mfundo ziwiri zosiyana: zotsatira zoyambirira mwa odwala zomwe zikudikira kutsimikizidwa ndi mayesero obisa magulu, ndi njira yogwirira ntchito yomwe ikudikira kutsimikizidwa mwa anthu. Owerenga amene akutsatira zotsatira za kukumbukira pa ukalamba m’njira zambiri angafunenso kuwerenga methylene blue ndi kukumbukira pa ukalamba.