Metanoolimürgistuste kliiniline uuring: massiliste mürgistuste käsitlemine, ravi antidootidega ja pikaaegne prognoos

Väitekirja elektrooniline versioon ei sisalda publikatsioone.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

Eesti Haigekassa auditi „Sepsise ravi kvaliteet“ kokkuvõte

Taust ja eesmärgid. Eestis on 2010. aastast kasutusel raske sepsise ja septilise šoki ravijuhend. 2015. aastal korraldatud kliinilise auditiga hinnati sepsisehaigete käsitluse vastavust sellele juhendile 12 Eesti aktiivravihaiglas.Metoodika. Auditisse valiti 01.07.2013 kuni 30.06.2014 ravil olnud haigetest rahvusvahelise haiguste klassifikatsiooni 10. versiooni (RHK-10) alusel juhuvalimi põhimõttel kokku 271 juhtu. Põhjalikumalt analüüsiti 141 juhtu, kus raske sepsis või septiline šokk esines juba haiglasse saabumisel. Järgiti kliiniliste auditite käsiraamatus toodud metoodikat.Tulemused. Sagedasemad sepsise põhjused olid hingamisteede, urotrakti ja seedetrakti infektsioonid. 52% haigest olid vanuses üle 70 aasta. Patsiendi seisund hinnati saabudes üliraskeks või raskeks (triaažikategooria punane või oranž) vaid 33%-l. Verekülvid esimese tunni jooksul tehti 6%-l haigetest, esimese 4 tunni jooksul 48%-l. 21%-l jäid verekülviproovid võtmata. Antibiootikumravi alustati 6%-l juhtudest esimese tunni, 66%-l esimese 4 tunni jooksul. Laktaadi sisaldus veres oli mõõdetud vaid 53%-l haigetest. Infusioonravi said 21% patsientidest alla 500 ml, 30% 500–1000 ml ja 18% 1000–1500 ml. Valimi haiglasuremus oli 42,4% ja 6 kuu suremus 59,2%.Järeldused. Raske sepsise ja septilise šoki käsitluses on Eestis mõningaid puudusi. Vereja muude külvide tegemine ning antibakteriaalse ravi alustamine on sageli hilinenud. Laktaadi määramine väljaspool regionaalhaiglaid on lünklik. Infusioonravis kasutatakse soovitatust väiksemaid vedelikukoguseid.Tervishoiuteenuse osutajatel tuleks üle vaadata oma tegevusjuhendid ning viia need vastavusse Eesti ravijuhendiga. Verekülvide tegemiseks, empiirilise antibiootikumravi alustamiseks ning laktaadi määramiseks verest vajalikud vahendid peavad olema kohe kättesaadavad

Correction: The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014.

[This corrects the article DOI: 10.1371/journal.pone.0152676.]

The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014.

BACKGROUND:Outbreaks of methanol poisoning occur frequently on a global basis, affecting poor and vulnerable populations. Knowledge regarding methanol is limited, likely many cases and even outbreaks go unnoticed, with patients dying unnecessarily. We describe findings from the first three large outbreaks of methanol poisoning where Médecins Sans Frontières (MSF) responded, and evaluate the benefits of a possible future collaboration between local health authorities, a Non-Governmental Organisation and international expertise. METHODS:Retrospective study of three major methanol outbreaks in Libya (2013) and Kenya (May and July 2014). Data were collected from MSF field personnel, local health personnel, hospital files, and media reports. FINDINGS:In Tripoli, Libya, over 1,000 patients were poisoned with a reported case fatality rate of 10% (101/1,066). In Kenya, two outbreaks resulted in approximately 341 and 126 patients, with case fatality rates of 29% (100/341) and 21% (26/126), respectively. MSF launched an emergency team with international experts, medications and equipment, however, the outbreaks were resolving by the time of arrival. INTERPRETATION:Recognition of an outbreak of methanol poisoning and diagnosis seem to be the most challenging tasks, with significant delay from time of first presentations to public health warnings being issued. In spite of the rapid response from an emergency team, the outbreaks were nearly concluded by the time of arrival. A major impact on the outcome was not seen, but large educational trainings were conducted to increase awareness and knowledge about methanol poisoning. Based on this training, MSF was able to send a local emergency team during the second outbreak, supporting that such an approach could improve outcomes. Basic training, simplified treatment protocols, point-of-care diagnostic tools, and early support when needed, are likely the most important components to impact the consequences of methanol poisoning outbreaks in these challenging contexts

Frequency methanol poisonings in Eldoret, Kenya, July 2014.

<p>Source: MSF field report.</p

Frequency of methanol poisonings in Kapsabet, Kenya, July 2014.

<p>Source: MSF field report.</p

Consensus statements on the approach to patients in a methanol poisoning outbreak

BACKGROUND: Methanol poisoning is an important cause of mortality and morbidity worldwide. Although it often occurs as smaller sporadic events, epidemic outbreaks are not uncommon due to the illicit manufacture and sale of alcoholic beverages. OBJECTIVE: We aimed to define methanol poisoning outbreak (MPO), outline an approach to triaging an MPO, and define criteria for prioritizing antidotes, extracorporeal elimination treatments (i.e., dialysis), and indications for transferring patients in the context of an MPO. METHODS: We convened a group of experts from across the world to explore geographical, socio-cultural and clinical considerations in the management of an MPO. The experts answered specific open-ended questions based on themes aligned to the goals of this project. This project used a modified Delphi process. The discussion continued until there was condensation of themes. RESULTS: We defined MPO as a sudden increase in the number of cases of methanol poisoning during a short period of time above what is normally expected in the population in that specific geographic area. Prompt initiation of an antidote is necessary in MPOs. Scarce hemodialysis resources require triage to identify patients most likely to benefit from this treatment. The sickest patients should not be transferred unless the time for transfer is very short. Transporting extracorporeal treatment equipment and antidotes may be more efficient. CONCLUSION: We have developed consensus statements on the response to a methanol poisoning outbreak. These can be used in any country and will be most effective when they are discussed by health authorities and clinicians prior to an outbreak