Clinical study of methanol poisoning: handling large outbreaks, treatment with antidotes, and long-term outcomes
Date
2013-09-27
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Abstract
Olles üks mürgisemaid alkohole põhjustab metanool aastas sadade ja tuhandete inimeste surma üle kogu maailma. Mürgistusjuhtumid metanooliga on ka Eesti jaoks aktuaalne probleem – kümneid inimesi aastas vajab selle tõttu haiglaravi ning paljud neist hukkuvad. 12 aastat tagasi tabas Pärnu- ja Läänemaad ulatuslik mürgistustelaine – mõne päeva jooksul hospitaliseeriti Pärnu Haiglasse 154 metanooli mürgistuse kahtlusega patsienti. Nii suure hulga kannatanute üheaegne ravi tõstatas haigla jaoks mitmeid korralduslikke probleeme, samas aga oli ka väärtuslik uurimismaterjal metanoolimürgistuse kliiniliste sümptomite, prognoosi määravate faktorite ning ravi kaugtulemuste analüüsimiseks. Käesolev uurimistöö tegelebki nende aspektidega.
Suurõnnetuse ravitulemusi analüüsides selgus, et haiglasse jõudnud patsientidest ligi pooled paranesid ilma tüsistusteta. Haiglasuremus oli 23 %, mis on samas suurusjärgus kirjanduses varem kirjeldatud analoogsete puhangutega. Märkimisväärne hulk kannatanuid aga hukkus haiglaeelselt enne meditsiinilise abi kohalejõudmist. Peamised tüsistused, mis tekkisid metanoolimürgistuse tulemusena, olid nägemis- ja närvisüsteemi kahjustused. Kuus aastat pärast mürgistust läbi viidud järelkontrollis ilmnes, et nimetatud kahjustused olid püsivad.
Doktoritöös on lisaks Eesti patsientidele kogutud andmeid metanoolimürgistuste kohta Norrast, Tuneesiast ja Iraagist. Tulemuseks on unikaalne rahvusvaheline toksikoloogia-alane andmebaas, mis võimaldas kindlaks teha ja analüüsida metanoolimürgistuse prognoosi määravaid tegureid. Oodatavalt ilmnes, et sügav teadvusehäire ning vere madal pH haiglasse jõudmisel olid peamised halba ravitulemust ennustavad näitajad. Olulise uue teadmisena lisandus arusaam, et patsiendi võime hüperventileerida mürgistuse tõttu tekkinud atsidoosi kompensatsiooniks määrab oluliselt haige prognoosi. Seda tuleb eriti arvesse võtta olukordades, kus patsient on kooma tõttu juhitaval hingamisel ning ventilatsiooni parameetrid on arsti otsustada.
Rahvusvaheline andmebaas võimaldas analüüsida ka kahe erineva antitoodi – etanooli ja fomepisooli – efektiivsust metanoolimürgistuse ravis. Tulemuste põhjal võib fomepisooli pidada mõnevõrra eelistatumaks, lisaks on tema manustamine lihtsam ning turvalisem.
Metanooli toksilise toime uurimine katseloomadel ei ole liikidevahelise erisuse tõttu võimalik. Seetõttu annab rahvusvahelises koostöös käesolevasse doktoritöösse koondatud kliiniline materjal olulise täienduse antud probleemistiku uurimisse ning kliinilise toksikoloogia arengusse.
Methanol is a highly toxic alcohol killing hundreds or even thousands of people every year worldwide. Even in Estonia, more than ten patients are on average hospitalised every year. During nine days in September 2001, a large outbreak of methanol poisonings occurred in the Western part of Estonia: A total of 154 patients were admitted to the local hospital, challenging not only the local resources, but the whole Health care system in Estonia as such. In parallel to treating all these patients, a systematic collection of data was initiated to evaluate the patients, the treatment that were given, and their outcome. Half of the admitted patients were discharged from hospital in a healthy condition, whereas 23% of the hospitalized patients died. In addition to those victims, many patients were found dead outside hospital without ever making it to any medical support. We searched for the survivors from the outbreak six years later, and found that all patients discharged with either visual or neurological impairment still suffered from this. The Estonian data were merged with similar data from methanol outbreaks in Norway, Iran and Tunisia, to look for relevant markers that can predict the patients’ outcome already when they are admitted to hospital. We found that being unconscious on admission to hospital was associated with a bad prognosis, as well as being very acidic in their blood. Finally, we found that the patients that were able to breath very fast to compensate for their acidic blood had a better prognosis than the ones that were not able to. International database gives us opportunity to evaluate the effectiveness of the to alternative antidotes on the market: fomepizole (the new antidote) and ethanol/regular alcohol (the old antidote) In spite of this study having the largest number of patients ever presented, the number was still too small to show any definite difference in outcome. However, fomepizole appeared to have various advantaged over ethanol, and it is clearly superior in simplicity and safety of the treatment. Methanol poisonings is a relatively infrequent condition, making collection of data to gain knowledge a difficult task. This thesis shows the importance of international collaboration between specialists to improve the chances for survival of these patients.
Methanol is a highly toxic alcohol killing hundreds or even thousands of people every year worldwide. Even in Estonia, more than ten patients are on average hospitalised every year. During nine days in September 2001, a large outbreak of methanol poisonings occurred in the Western part of Estonia: A total of 154 patients were admitted to the local hospital, challenging not only the local resources, but the whole Health care system in Estonia as such. In parallel to treating all these patients, a systematic collection of data was initiated to evaluate the patients, the treatment that were given, and their outcome. Half of the admitted patients were discharged from hospital in a healthy condition, whereas 23% of the hospitalized patients died. In addition to those victims, many patients were found dead outside hospital without ever making it to any medical support. We searched for the survivors from the outbreak six years later, and found that all patients discharged with either visual or neurological impairment still suffered from this. The Estonian data were merged with similar data from methanol outbreaks in Norway, Iran and Tunisia, to look for relevant markers that can predict the patients’ outcome already when they are admitted to hospital. We found that being unconscious on admission to hospital was associated with a bad prognosis, as well as being very acidic in their blood. Finally, we found that the patients that were able to breath very fast to compensate for their acidic blood had a better prognosis than the ones that were not able to. International database gives us opportunity to evaluate the effectiveness of the to alternative antidotes on the market: fomepizole (the new antidote) and ethanol/regular alcohol (the old antidote) In spite of this study having the largest number of patients ever presented, the number was still too small to show any definite difference in outcome. However, fomepizole appeared to have various advantaged over ethanol, and it is clearly superior in simplicity and safety of the treatment. Methanol poisonings is a relatively infrequent condition, making collection of data to gain knowledge a difficult task. This thesis shows the importance of international collaboration between specialists to improve the chances for survival of these patients.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone.
Keywords
mürgistused, metanool, sümptomid, ravitulemused, poisonings, methanol, symptoms, results of treatment