INTOXICACIONPOR METANOL

INTOXICACION POR METANOL?

Whisky Atlanta 195190 galones de whisky40% metanol 323 altas41 muertesBennett et al: Acute methanol poisoning. Medicine 1953;32:431-457.

LATACUNGA30 de diciembre de 19785 galones contaminadosMuertos?Ciegos?Secuelas SNC ?

Compuestos con metanolSolventesRemovedor de pinturasFluidos de fotocopiadorasAnticongelantesAdhesivosCristales inastillables

QumicaCH3OHAlcohol metlico, nafta de madera espritu pilroligenoso, carbinol, TRAGO DE CARPINTERO

ConcentracionesVino300 mg/dLBrandy y otros > 300Ambiente rural10 ppbAmbiente urbano30 ppbParqueos y miles de vecesresidencias

MetabolismoAbsorcin GI100 %Retencin en pulmn 60 %Distribucin en agua corporal100 %PielRelacionado con integridad y mezcla

Dosis bajas 3 horasDosis txicas sobre 30 horas Vida media

Metabolismo paso 1

Metabolismo paso 2

Metabolismo paso 3FOLATO

EthanolMethanolEthylene GlycolGlycoxylate (lactic acidosis)Glycoaldehyde (CNS effects)Glycolic Acid (metabolic acidosis)Oxalate (cerebral & renal damage, hypocalcaemia)Formic Acid (metabolic acidosis)Acetaldehyde (hangover, flushing)Formaldehyde (blindness, cerebral oedema)Acetic AcidAlcohol DehydrogenasaAldehyde DehydrogenaseLactate dehydrogenase or glycolic acid oxidaseLactate dehydrogenase or aldehyde oxidaseCO2 + H20

Efectos fisiolgicosDosis letal1 - 2 ml/kgMuerte y ceguera0.1 ml/kg ( 6 - 10 ml )Efectos agudosAcidosis metablicanecrosis del N. ptico polineuropata, hemorragia del putamen , sindrome extrapiramidalEfectos crnicosCardiognicos

Cuadro clnicoExposicin crnicaOftalmolgicosIrritacin ocular , visin borrosaPulmonaresIrritacin de la va area superiorSNCCefalea, nusea, inestabilidadPielIrritacin

Cuadro clnicoExposicin agudaTrastornos ocularesVisin borrosa, escotomas, visin central o perifrica alterada, midriasis con baja respuesta a la luz, acomodacin normal, papiledema, necrosis y atrofia del nervio ptico

Diagnstico diferencial de la cegueraMetanolQuininaMonxido de carbono

Cuadro clnicoExposicin aguda

( Na+ + K+ ) - ( HCO3 - + Cl- ) = 12 -16 mEq/L

( Na+ ) - ( HCO3 - + Cl- ) = 8 - 12 mEq/L Anion GAP

Condiciones que elevan el anion-gapC yanide, carbon monoxideA lchololic ketoacidosisT olueneM ethanol ingestionU remiaD iabetic ketoacidosisP araldehyde, phenforminI nborn errors iron, INH, inhalantsL actic acidosisE thylene glycol, ethanolS alicylates, solvents

Osmolar GAP BUN Gluc 2 Na + + = 285 +4 2.8 18 MAS = ???????? Etanol mg d/L 4.6

LaboratorioOsmolar gap elevadoConcentraciones de 100 mg/dLMETANOL33.7Etanol22.8Etilnglicol19.0Acetona18.2Salicilatos 6.0

Condiciones que elevan el osmolar gapM anitolA lcohols (Et, EG, Meth,Isop)D iatrozateG lycerolA cetoneS orbitol

Clculo del nivel srico de metanolNivel sanguneo estimado = Brecha Osmolar x 2.6

mg/dL

LaboratorioIndicador directoMetanol endgeno0.05 mg/dLT. Neurolgicos 20 mg/dLT. Oculares100 mg/dLMUERTE150 - 200 mg/dLNivel urinario aceptado15 mg/dL

Metas del tratamiento Descontaminacin Bloquear el metabolismo Degradar al formato Corregir la acidosis

TratamientoDosificacin srica de metanol y etanolDeteccin temprana 30 - 45 minutosPaciente concienteEmesis Lavado gstricoMantener pH 7.36 - 7.40

TratamientoMedidas GeneralesABCsMedidas especficasEtanol y 4 Metil pirazol para BLOQUEAR la alcohol deshidrogenasa.Acido flico y leucovorn para BLOQUEAR el formato

Tenga en cuenta que:

Tenga en cuenta que:

TratamientoEtanol 10 % IV( Peso especfico 0.8 g/ml ====> 1g = 1.25 ml )Dosis de carga 0.6 g/kg en 20 - 60 minutosDosis de mantenimiento 66 - 130 mg/kg/hora MANTENER NIVEL SERICO 100 - 150 mg/dL

ETANOL IV Paciente 70 kgDosis de CargaRp:70 ml etanol630 ml D/A 5 %MantenimientoInfusin continua de la misma solucina 91 ml/h.

Dilisis 245 ml/hIV en 1H

TratamientoEtanol 20 % VO( 100 Proof = 50 % )Dosis de carga 0.8 g/kg ==> 350 mlDosis de mantenimiento 80 - 130 mg/kg/h ==> 40-60 ml Hemodilisis 250 - 350 mg/kg/hMANTENER NIVEL SERICO 100 - 150 mg/dL

ETANOL VO Paciente 70 kgCARGA 175 ml statMantenimiento 23 ml/hDilisis 70 ml/h

TratamientoAcido flico 50 - 70 mcg c/4 h por 24 hLeucovorn IV 1 - 2 mg/kg c/6 h por 24 h4 Metilpirazol VO Carga 15 mg/kgSeguido de 5 mg/kg en 12 hLuego 10 mg/kg cada 12 h

TratamientoHemodilisisMetanol 50 mg/dLFormato 20 mg/dLAcidosis refractariaEtanol 10% IV 250-350 mg/kg/hMANTENER NIVEL SERICO 100 - 150 mg/dL

**The principles of treatment are twofold:1st to block the metabolism of methanol to its toxic and acidic metabolites, and 2nd to enhance removal of methanol and any toxic metabolites already formed, from the body

But before we look the effect of the dual therapy of Ethanol and Dialysis used in this case, it is useful to look at the metabolism of alcohols, focusing on Methanol.

All 3 alcohols are initially metabolised by the same enzymes- Alc DH and Aldehyde DH. With the conversion by Alc DH being the rate limiting stepIn the case of methanol the relatively non-toxic alcohol is first metabolised to the highly toxic formaldehyde, Before being rapidly converted to formic acid - producing a metabolic acidosis.

Although MeOH and EtOH are both metabolised by AlcDH. Methanol has a much lower affinity for the enzyme being oxidised at a rate of 1/7th that of Ethanol. Therefore a latent period of 12-24h can occur before classical signs and symptoms MeOH poisonings may present, as in this case.

This increased affinity of ethanol even in the presence of Methanol has allowed Ethanol to be used as an antidote, acting as a competitive substrate, thus occupying the Alc DH and preventing the metabolism of methanol.

However blocking the metabolism of methanol is only half the problem, because more than 97% of Methanol is cleared from the body by the action of Liver ALD, a route that we have just blocked, and via the remaining routes of excretion alone renal and pulmonary it would take a significantly long time the clear the high levels of methanol such as in this patient, requiring constant and continuing ethanol therapy and monitoring, therefore Haemodialysis is used.

In recent years a new antidote - Formepizole (4-methpyrazole), an Alcohol DH inhibitor has been licensed for use in the treatment of methanol & EG poisonings, instead of using ethanol.

ER a couple of weeks ago (where I get a significant amount of medical education it a bit like watching the open university, except the people and the clothes are much better looking!)Formepizole (4-methpyrazole) ADH inhibitor