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Vol. 28. Issue. 4.August 2008
Pages 361-473
Vol. 28. Issue. 4.August 2008
Pages 361-473
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Effectiveness of pre-emptive hemodialysis with high-flux membranes for the treatment of lifethreatening alcohol poisoning
Eficacia de la hemodiálisis precoz con membranas de alto flujo en el tratamiento de las intoxicaciones graves por alcoholes
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Ramón Pecesa, Elena Gonzáleza, Elena Olivasa, Fernando Renjela, Olga Costeroa, Agustín Monteroa, Rafael Selgasa, Raquel Fernándezb, Manuel Jiménezb, Carlos Pecesc
a Servicio de Nefrología, Hospital Universitario La Paz, Madrid, Madrid, España,
b Unidad de Cuidados Intensivos, Hospital Universitario La Paz, Madrid, Madrid, España,
c Área de Tecnología de la Información, SESCAM, Toledo, Toledo, España,
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La intoxicación por alcoholes (metanol, etanol y etilenglicol) origina acidosis metabólica severa con hiato aniónico y osmolal elevados, alteraciones neurológicas que van desde la obnubilación al coma profundo, amaurosis, y muerte. A pesar de la terapia intensiva la morbilidad y la mortalidad siguen siendo muy elevadas. En la intoxicación por etilenglicol, además, puede ocurrir la precipitación masiva de oxalato en los tejidos, sobre todo en el riñón, produciendo un fracaso renal agudo. El tratamiento establecido, en las intoxicaciones por metanol y etilenglicol, es la administración de etanol y la hemodiálisis (HD) precoz. La HD convencional puede reducir rápidamente los niveles de metanol, etanol y etilenglicol, así como los de sus metabolitos tóxicos, corrigiendo también los trastornos electrolíticos y ácido-base. Las membranas de alto flujo son capaces de eliminar más cantidad de tóxico por hora de HD pudiendo ser más eficaces en el tratamiento. En este estudio se presentan 14 casos de intoxicación por alcoholes (11 metanol, 1 etanol y 2 etilenglicol) tratados precozmente con bicarbonato, infusión de etanol (para metanol y etilenglicol) y HD con membranas de alto flujo. Al ingreso el pH medio fue 7,04 ± 0,06 (rango 6,60-7,33), el bicarbonato medio de 9,9 ± 1,9 mmol/l (rango 1,4-25) y el déficit de bases medio de 18,4 ± 2,6 mmol/l (rango 2-33). El hiato aniónico inicial fue de 29,1 ± 2,3 mmol/l (rango 16-45) y el hiato osmolal de 119 ± 47 mOsm/l (rango 16-402). Existió una excelente correlación lineal entre los niveles séricos iniciales del alcohol tóxico y el hiato osmolal (R2 = 0,98, p = 0,0006). En todos los casos, el tratamiento precoz con HD corrigió la acidosis metabólica y el hiato osmolal. De los 14 casos, 11 sobrevivieron sin secuelas, 2 quedaron con amaurosis y 1 falleció (mortalidad 7 %). Se concluye que en las intoxicaciones severas por alcoholes la HD debe instaurarse precozmente. La infusión de etanol, al frenar el metabolismo del metanol y del etilenglicol, permite la eliminación rápida por HD de los alcoholes y sus metabolitos tóxicos. La prescripción de HD debe incluir un dializador de alto flujo y gran superficie, un flujo sanguíneo elevado, un baño de bicarbonato con concentraciones normales de potasio y fósforo, y debe prolongarse el tiempo necesario. La modificación del baño de HD evita la hipofosfatemia y la hipopotasemia. La HD según fue implementada en estos casos es una forma segura y efectiva de tratamiento de la intoxicación grave por alcoholes.
Palabras clave:
Hiato osmolar
Palabras clave:
Hiato aniónico
Palabras clave:
Hemodiálisis de alto flujo
Palabras clave:
Etanol
Palabras clave:
Etilenglicol
Palabras clave:
Acidosis metabólica
Palabras clave:
Metanol
Palabras clave:
Alcohol intoxication (methanol, ethanol and ethylene glycol) may result in metabolic acidosis with increased anion gap, increased serum osmolal gap, and neurologic abnormalities ranging from drunkenness to coma, and death. The mortality and morbidity rates remain very high despite intensive care therapy. The toxicity of methanol and ethylene glycol is clearly correlated to the degree of metabolic acidosis. The established treatment of severe methanol and ethylene glycol intoxication is ethanol administration and hemodialysis (HD). By inhibiting the main metabolic pathway of methanol and ethylene glycol (alcohol dehydrogenase), ethanol prevents the formation of major toxic metabolites (formic acid, glycolic acid and oxalic acid). Conventional HD can reduce serum methanol, ethanol and ethylene glycol and its metabolites rapidly, but high-flux membranes should be capable of removing more toxic per hour of HD. In this report, we describe 14 cases of life-threatening alcohol intoxication (11 methanol, 1 ethanol, and 2 ethylene glycol) who were treated successfully with supportive care, ethanol infusion (methanol and ethylene glycol), and early HD with a high-flux dialyser. The median pH was 7.04 ± 0.06 (range 6.60-7.33), median bicarbonate 9.9 ± 1.9 mmol/l (range 1.4-25), and median base deficit 18.4 ± 2.6 mmol/l (range 2-33). The median anion gap was 29.1 ± 2.3 mmol/l (range 16-45) and the median osmolal gap was 119 ± 47 mOsm/l (range 16-402). On admission there was an excellent linear correlation between the serum toxic alcohol concentrations and the osmolal gaps (R2 = 0.98, p = 0.0006). In all cases early HD corrected metabolic acidosis and osmolal abnormalities. The mortality was 7% (1 from 14). We conclude that pre-emptive HD should be performed in severe intoxications to remove both the parent compound and its metabolites. The HD prescription should include a large surface area dialyser with high-flux membrane, a blood flow rate in excess of 250 ml/min, a modified bicarbonate bath enriched with phosphorus and potassium, and a long time session. The phosphorus and potassium- enriched bicarbonate-based dialysis solution used in patients with normal phosphorus and potassium serum levels avoided HD-induced hypophosphatemia and hypopotassemia. HD as implemented in these cases is a safe and very effective approach to the management of alcohol poisoning.
Keywords:
Osmolal gap
Keywords:
Anion gap
Keywords:
High-flux membranes
Keywords:
Ethanol
Keywords:
Ethylene glycol
Keywords:
Metabolic acidosis
Keywords:
Methanol
Keywords:
Hemodialysis
Full Text

INTRODUCTION

Poisoning induced by alcohols (methanol, ethanol, and ethylene glycol) may cause neurological changes ranging from confusion to deep coma, amaurosis, and death. Despite intensive treatment, morbidity and mortality continue to be very high, mainly because of the delay in diagnosis and treatment.1-6 Toxicity from methanol, ethanol, and ethylene glycol is related to the degree of metabolic acidosis and the increase in plasma osmolality induced.1-3 By inhibiting the main metabolic pathway of methanol and ethylene glycol, alcohol dehydrogenase (ADH), ethanol, and fomepizole prevent the formation of the main toxic metabolites, formic acid from methanol and glycolic and oxalic acids from ethylene glycol.7 The established treatment for severe poisoning by methanol and ethylene glycol is administration of ethanol and pre-emptive HD.1-7 Conventional HD treatment may rapidly decrease levels of methanol, ethanol, and ethylene glycol, as well as their metabolites, and also correct electrolyte and acid-base
disorders, but high-flux membranes may remove a greater amount of toxic per hour of HD, increasing its efficacy [8]. The study objective was to prospectively analyze the effectiveness of therapeutic measures, including dialysis, in cases of poisoning by these alcohols where an early treatment protocol including bicarbonate administration, ethanol infusion, HD using high-flux membranes, and a modified bath to prevent hypophosphatemia and hypokalemia was used.

MATERIALS AND METHODS

Data from 14 patients admitted to our hospital in the past 3 years for poisoning with methanol (11), ethanol (1), and ethylene glycol (2) are reported. Initial diagnosis was made based on a clinical history with sufficient evidence of intake of toxic alcohols (statements from patients themselves or witnesses, and containers brought with residues of toxics ingested), as well as the presence of metabolic acidosis with elevation of the anion and/or osmolal gaps. In addition, whenever possible, serum levels (as well as urinary and gastric juice levels in some cases) of the corresponding toxic alcohols were measured by gas chromatography (National Institute of Toxicology and Forensic Science, Ministry of Justice, Madrid). Routine procedures were used to test all other biochemical parameters such as electrolytes, osmolality, arterial blood gases, etc. on arrival to the emergency room, before the start and at the end
of dialysis treatment, and throughout the course. Anion gap was calculated using the standard formula (Na+ + K+) ¿ (Cl- + HCO3 -), and osmolal gap by subtracting from the osmolality measured (osmometer) the osmolality calculated with the standard formula. Calculated serum osmolality (mOsm/L) = 2 x Na + Urea (mg/dL)/6 + glucose (mg/dL)/18.

To correct metabolic acidosis, 100 to 300 mL of 1 M sodium bicarbonate and 1,000 mL of isotonic saline were initially infused to all patients. Repeat infusion of 1 M sodium bicarbonate was required in some cases to maintain bicarbonate levels at safe levels until HD was started. As fomepizole was not available, ethanol infusion was used to inhibit ADH in patients with methanol and ethylene glycol poisoning. Treatment was started with a loading dose of ethanol (750 mL of a 10% solution in 5% glucose) over 30 minutes. A 10% ethanol infusion at 100 mL/h was subsequently administered. During the HD session, ethanol infusion was increased to 150-200 mL/h, and in some cases the 100 mL/h infusion was continued for 8-24 hours. In patients intoxicated by methanol, folic acid was administered IV at a dose of 20 mg/8 h to accelerate formate metabolism. In cases of ethylene glycol poisoning,
pyridoxine (50 mg/6 h IM) was administered to convert glyoxylate into glycine, and thiamine (100 mg/6 h IM&

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