3originally was manufactured from the distillation of wood. It is a product of :natural fermentationandoriginally was manufacturedfromthe distillation of wood.
4Certain products found in the home: including: antifreeze; gasohol; windshield washer fluid; dry gas; carburetor fluid; Sterno duplicator fluid; glass cleaners hobby engine fuel; lacquers thinners for shellacs adhesives inks may contain high concentrations of methanol. Methanol is a precursor in the manufacture of plastics, films, and dyes. Methanol is also found in formalin and embalming fluid.
10raki (Turkey):In Turkey, raki is the unofficial “national drink”. To serve raki it must be mixed with cold water; when it is mixed with water it turns to milky-white color. Because of that color raki is called as “aslan sütü” which means “lion’s milk”.
12making early recognition of clinical and laboratory clues crucial. Treatment delay is associated with increased morbidity,making early recognition of clinical and laboratory clues crucial.
13Methanol is absorbed rapidly from the gastrointestinal tract, andblood levelspeak30 to 60 minutesafter ingestion.
14respiratory tract absorption TransdermalAndrespiratory tract absorptionalso has resulted intoxicity,especially in infants.
15are at high risk for inhalational exposure to methanol. Certain occupations, includingpainting,glazing,varnishing,lithography, andprinting,are at high risk for inhalational exposure to methanol.Inhalational abuse of methanol is a recent trend that can result in toxic serum levels.
164 mL of pure methanol has led to blindness. In adults,the smallest lethal dosereported is15 mL of 40% methanol;4 mL of pure methanol has led to blindness.
17With appropriate, timely treatment, however, survival without loss of eyesight has been reported despite extremely high levels.
18From a pediatric perspective, the ingestion of only 1 From a pediatric perspective, the ingestion of only 1.5 mL of 100% methanol in a toddler (0.15 mL/kg) is sufficient to produce a toxic blood level of 20 mg/dL.
19Any suggested pediatric methanol ingestion warrants aggressive evaluation and treatment.
20CNS depression Less and inebriation than ethanol. Methanol itself has little toxicity, producingLessCNS depressionandinebriationthan ethanol.
21Metabolites of the parent alcohol are extremely toxic, however. Although small amounts of methanol are eliminated via renal and pulmonary routes, 90% is metabolized hepatically.
22Methanol is oxidized by alcohol dehydrogenase (ADH) to formaldehyde, which is rapidly converted by aldehyde dehydrogenase to formic acid.Formic acid is the primary toxicant and accounts for much of the anion gap metabolic acidosis and ocular toxicity peculiar to methanol ingestion. Through a folate-dependent pathway, formic acid is degraded to carbon dioxide and water.
24two main complications Pathophysiology:Optic neuropathyAndputaminal necrosisare thetwo main complicationsofsevere methanol poisoning.
25Long-term morbidity: parkinsonian motor dysfunction, takes the form of:visual impairment,including:blindness,parkinsonian motor dysfunction,characterized by:hypokinesisrigidity.
26The primary sites of ocular injury are the retrolaminar optic nerve and retina.
27Methanol adversely affects other areas of the CNS, specifically the basal ganglia. Bilateral, symmetrical putaminal hypodensities, hemorrhages, or cystic lesions are characteristic, occurring in 13.5% of patients.Necrosis is described in the:subcortical white matter,spinal cord anterior horn cells,cerebellum.Acute signs and symptoms may be lacking or may take several days to develop, despite the presence of these radiographic findings.
29With individual cases of methanol poisoning, the history may be unobtainableunreliableThe diagnosis should be considered in patients withaltered mental status,visual complaints, ormetabolic acidosis orin patients with occupationsthat put them at high risk for exposure.
30gastrointestinal, or ocular. The typical 12- to 24-hour latency may be shorter when large amounts are consumed or longer when ethanol is co-ingested (range 40 min to 72 hr).When symptoms manifest, they are primarilyneurologic,gastrointestinal, orocular.
31weakness, dizziness, anorexia, headache, nausea. Although methanol is less inebriating than ethanol,early symptoms of methanol poisoning are:depressed mental status,confusion,ataxia.Nonspecific complaints of:weakness,dizziness,anorexia,headache,nausea.
32In severe cases,comaseizures may be seen.Although vomiting andabdominal paincommonly result from mucosal irritation, the absence of gastrointestinal complaints does not rule out a serious ingestion
33Visual disturbances are seen in 50% of patients, and their development may precede or parallel that of other clinical symptoms.Patients may complain ofcloudy,blurred,indistinct, ormisty vision ormay note yellow spotsphotophobia.
34The most common acute field defect is a dense central scotoma. Some patients compare their visual symptoms with “stepping out into a snowstorm,” a complaint unique to methanol ingestion.Patients can have a complete lack of light perception and total loss of vision.
35Prognosis after methanol ingestion seems to correlate with: the degree of acidosis,time to presentation,initiation of treatment within 8 hours of exposure
36Poor prognosis is associated with coma, seizures, arterial pH less than 7.0.A recent large outbreak was associated with a fatality rate of 44%
37Patients surviving the acute phase of toxicity may be left with: permanent blindness orneurologic deficits, such as:parkinsonism,toxic encephalopathy,polyneuropathy,cognitive dysfunction,transverse myelitis,primitive reflexes, orseizures.
39A severe anion gap metabolic acidosis is the hallmark of methanol poisoning. In some cases, this sign may be the only diagnostic clue.Because the onset of acidosis may be delayed 12 to 24 hours, the presence of a normal anion gap does not rule out methanol exposure.
40Absence of high anion gap acidosis has been described in cases with: ethanolconcomitant lithium ingestion.bromideIn methanol toxicity, this anion gap is due primarily to the presence of formic acid, with a variable contribution from lactic acid.
41Osmol gap= measured serum osmolality- calculated serum osmolality Another classic laboratory finding in methanol toxicity is an elevated osmol gap. The osmolal gap is defined as follows:Osmol gap= measured serum osmolality- calculated serum osmolalityAn osmol gap significantly greater than 10 mOsm/kg may be a useful aid in the diagnosis of toxic alcohol ingestion.
42delayed presentation after toxic alcohol ingestion may be associated with prior metabolism of most of the parent alcohol.Because only the parent compound is osmotically active, andBecause the charged metabolites are electrically balanced by sodium,there may be little or no osmol gap elevation in this setting.
43If there is clinical suggestion of toxic alcohol ingestion, direct measurement of the serum toxic alcohol level is necessary, and if not readily available, empirical treatment is warranted.
44Rhabdomyolysis, pancreatitis, and metabolic derangements, such as: hypomagnesemia,hypokalemia,hypophosphatemia,are also described with methanol poisoning.
45Computed tomography may be indicated in an intoxicated patient with altered mental status.
47For any significant history of exposure, treatment should be initiated pending a confirmatory toxic alcohol blood level.
48Because methanol is absorbed rapidly from the GI tract, gastric emptying is restricted to patients who have ingested a substantial volume and arrive in the emergency department within 30 to 60 minutes of ingestion.
50Forced diuresis is of no value and may cause pulmonary edema and ARDS. Early intubation may be indicated to protect the airway against aspiration and in anticipation of further deterioration in mental status.
51(3) removal of the parent alcohol and its metabolites by hemodialysis. Three treatment goals exist for patients with methanol toxicity:(1) correction of metabolic acidosis with bicarbonate;(2) ADH enzyme blockade, which inhibits the metabolism of methanol to toxic metabolites; and(3) removal of the parent alcohol and its metabolites by hemodialysis.
52Depending on the severity of the patient's acidosis, IV bicarbonate can be administered by intermittent boluses, an initial bolus followed by an infusion, or infusion alone.Boluses of 1 to 2 mEq/kg to attain a target serum pH of 7.45 to 7.50 followed by an infusion of 150 mEq/L of sodium bicarbonate in 5% dextrose at 1.5 to 2 times the maintenance fluid rate are suggested.
53To prevent further production of the toxic and acidic metabolites of methanol and ethylene glycol, metabolism of the parent compounds by the enzyme ADH must be blocked by either ethanol or fomepizole (Antizol).After significant toxic alcohol exposure, ADH blockade should be carried out in any adult or child with symptoms or with methanol or ethylene glycol levels greater than 20 mg/dL, even if asymptomatic.
55If ethanol is used to block ADH, the goal is to maintainthe blood ethanol level between 100 and 150 mg/dL,which completely saturates ADH.The affinity of ADH for ethanol is 10 to 20 times greater than for methanol and 100 times greater than for ethylene glycol.
56When methanol or ethylene glycol metabolism is blocked by ethanol, their half-lives increase to more than 30 hours or 17 hours.
57When dosing ethanol, it also is important to measure the patient's initial blood ethanol level. If it is greater than 100 mg/dL, a loading dose is unnecessary, and the patient can be started on a maintenance infusion.The required maintenance dose of ethanol may nearly triple during hemodialysis because ethanol also is efficiently removed.
58hypotension, vomiting, hypoglycemia, and thrombophlebitis, Ethanol may be given orally or intravenously.Potential side effects of IV administration includeCNS and respiratory depression,hypotension,vomiting,hypoglycemia, andthrombophlebitis,although even in children, adverse effects are limited.Oral ethanol loading may be associated with gastritis.
59Levels should be checked every 2 to 4 hours thereafter. Initial close monitoring of serum ethanol and glucose levels every 1 to 2 hours is essential until a steady-state level of 100 to 150 mg/dL is achieved.Levels should be checked every 2 to 4 hours thereafter.Monitoring of ethanol therapy ideally is accomplished in the intensive care unit.
60Standard Range of Therapeutic Doses of Ethanol Based on Average Pharmacokinetic Values:
61Mixing 50 mL of absolute ethanol with 450 mL isotonic glucose yields a 10% solution if a 10% ethanol solution for IV use is unavailable.With this solution, a bolus of 8 mL/kg (over 0.5 hour), followed by 1.5 mL/kg/hr, will produce the desired ethanol concentration. The maintenance infusion should be increased or decreased according to frequently measured ethanol levels.As a rule of thumb, the maintenance dose of ethanol should be doubled during hemodialysis. If not, methanol metabolism can resume when the ethanol level drops, resulting in worsening toxicity despite hemodialysis.
62Similar to ethanol, fomepizole blocks the metabolism of methanol and ethylene glycol by ADH and prevents the formation of toxic metabolites.When methanol or ethylene glycol metabolism is blocked by fomepizole, their half-lives increase to an average of 52 and 17 hours.
63Fomepizole is a pregnancy category C drug; although not approved for use in children, its use has been reported.
64Simply blocking toxic alcohol metabolism does not alter the toxicity of preformed metabolites. The use of neither fomepizole nor ethanol supplants the need for hemodialysis.
65Fomepizole Approved by FDA for E.G. poisoning in 1997, and for methanol poisoning in 2000
66FomepizoleFomepizole has an affinity for the enzyme that is 8000 times that of ethanol.In addition, it does not produce central nervous system depression or metabolic toxicity, and it does not require the monitoring of levels and dosage adjustments.
67Fomepizole:The dose is 15 mg/kg followed by 10 mg/kg every 12 hours for four doses.After five doses, the dose increases to 15 mg/kg every 12 hours until the Methanol concentration is undetectable or less than 20 mg/dL and the patient is asymptomatic with a normal arterial pH.Dosing changes are required during hemodialysis.
68Side effects of fomepizole: headache,nausea,dizziness,inflammation at the site of infusion,rash,eosinophilia,mild, reversible transaminase elevation.
69Rapid removal of the methanol or ethylene glycol through hemodialysis before they have been metabolized remains the cornerstone of therapy.
70hemodialysis is indicated in: patients who have metabolic acidosis, renal compromise, visual symptoms (methanol), deterioration despite intensive supportive care, electrolyte imbalances unresponsive to conventional therapy. a blood level of either substance greater than 50 mg/dl but in patients with normal kidneys, prolonged fomepizole treatment alone has been used without hemodialysis
71Indications for Dialysis with Methanol Poisoning :
72The endpoint for hemodialysis: an undetectable serum ethylene glycol or methanol concentration &the disappearance of acid-base abnormalities &the disappearance of signs of systemic toxicity.Closure of the anion gap also may serve as an endpoint for hemodialysis in situations in which levels are not available or reliable (i.e., in patients with delayed presentation).
73until the osmolal gap is normal in two samples 1 hour apart. If methanol analyses are unavailable:hemodialysis should be continued forat least 8 hoursoruntil the osmolal gap is normalin two samples 1 hour apart.
74In methanol poisoning, the rate of the final degradation reaction of formic acid to carbon dioxide and water depends on the cofactor folate.50 mg of leucovorin (folinic acid) should be given IV every 4 hours to adults with methanol toxicity.If folinic acid is unavailable, folic acid, in the same dose, can be used.