a) FOMEPIZOLE VS ETHANOL: Fomepizole is easier to use clinically, requires less monitoring, and does not cause CNS depression or hypoglycemia. Ethanol requires continuous administration and frequent monitoring of serum ethanol and glucose levels, and may cause CNS depression and hypoglycemia (especially in children). The drug cost associated with ethanol use is generally much lower than with fomepizole; however, other costs associated with ethanol use (continuous intravenous infusion, hourly blood draws and ethanol levels, possibly greater use of hemodialysis) may make the costs more comparable.
b) FOMEPIZOLE: Fomepizole is administered as a 15 mg/kg loading dose, followed by four bolus doses of 10 mg/kg every 12 hours. If therapy is needed beyond this 48 hour period, the dose is then increased to 15 mg/kg every 12 hours for as long as necessary. Fomepizole is also effectively removed by hemodialysis; therefore, doses should be repeated following each round of hemodialysis.
c) ETHANOL: Ethanol is given to maintain a serum ethanol concentration of 100 to 150 mg/dL. This can be accomplished by using a 5% to 10% ethanol solution administered intravenously through a central line. Intravenous therapy dosing, which is preferred, is 0.8 g/kg as a loading dose (8 mL/kg of 10% ethanol) administered over 20 to 60 minutes as tolerated, followed by an infusion rate of 80 to 150 mg/kg/hr (for 10% ethanol, 0.8 to 1.3 mL/kg/hr for a non-drinker; 1.5 mL/kg/hr for a chronic alcoholic). During hemodialysis, either add ethanol to the dialysate to achieve 100 mg/dL concentration or increase the rate of infusion during dialysis (for 10% ethanol, 2.5 to 3.5 mL/kg/hr). Oral ethanol may be used as a temporizing measure until intravenous ethanol or fomepizole can be obtained, but it is more difficult to achieve the desired stable ethanol concentration. The loading dose is 0.8 grams/kg (4 mL/kg of 20% {40 proof}) ethanol diluted in juice administered orally or via a nasogastric tube. Maintenance dose is 80 to 150 mg/kg/hour (of 20% {40 proof}) ethanol; 0.4 to 0.7 mL/kg/hour for a non-drinker; 0.8 mL/kg/hour for a chronic alcoholic). Concentrations greater than 30% (60 proof) ethanol should be diluted. For both modalities, blood ethanol levels must be monitored hourly and adjusted accordingly, and both require patient monitoring in an ICU setting.

a) Tachycardia may occur (Okuonghae et al, 1992).

a) CASE REPORT: Blood pressure of 105/60 mm Hg has been reported in a 15-year-old girl following the ingestion of 200 mL brake fluid containing 55% triethylene glycol and 10% DEG. Dobutamine infusion was used to support blood pressure (Borron et al, 1997).
b) CASE REPORT: Hypertension (170/100 mmHg) followed by hypotension (systolic 100 mmHg) occurred in a 29-year-old man following dermal application, over several months, of brake fluid, containing 10% diethylene glycol, to treat a "dermatitis" (Devoti et al, 2015).

a) Significant hypertension, refractory to drug treatment, has been reported in 3 fatalities due to ingestion of 2 to 3 cups of 100% diethylene glycol as an ethanol substitute. All 3 patients presented to the emergency department 6 days following the ingestions with delayed onset of symptoms. Death was due to renal failure (Doyle et al, 1998).
b) CASE SERIES: Hypertension occurred in 5 of 11 patients (45.5%) who ingested locally prepared antipyretic medications (daily doses ranging from 15 to 30 mL) containing acetaminophen and contaminated with diethylene glycol. The amount of diethylene glycol in the medications ranged from 2.3% to 22.3%. All 4 patients also developed acute renal failure and encephalopathy requiring ventilation (Hari et al, 2006).
c) CASE REPORT: Hypertension (170/100 mmHg) followed by hypotension (systolic 100 mmHg) occurred in a 29-year-old man following dermal application, over several months, of brake fluid, containing 10% diethylene glycol, to treat a "dermatitis" (Devoti et al, 2015).

a) Death may occur from sudden cardiorespiratory arrest. Respiratory failure requiring mechanical ventilation is a severe neurological manifestation of acute DEG poisoning (O'Brien et al, 1998).
b) CASE REPORT: A 29-year-old man presented with nausea, abdominal pain, weakness, hypertension, and anuria. Laboratory results revealed severe renal failure (serum creatinine 15.5 mg/dL, estimated glomerular filtration rate (eGFR) 4.3 mL/min/1.73 m2), elevated transaminase concentrations, elevated serum lipase concentration, and metabolic acidosis. Interview of the patient's family revealed that he had been applying brake fluid, containing 10% diethylene glycol, to his skin for several months to treat a "dermatitis". Despite supportive therapy, including hemodialysis and continuous venovenous hemofiltration, the patient developed progressive drowsiness, hypotension, and respiratory failure necessitating intubation and mechanical ventilation. A renal biopsy was performed which indicated acute toxic proximal tubular necrosis without oxalate crystals. Over the next several days, the patient's neurologic status deteriorated with the development of ascending paralysis, areflexia, loss of corneal, vestibulo-ocular, and gag reflexes, and coma (Glasgow Coma Scale score of 3). With continued supportive care, the patient's neurologic and renal function gradually improved, with normalization of renal function parameters (serum creatinine of 1.26 mg/dL and eGFR 89 mL/min/1.73) approximately 33 days post-admission. Following transfer to a rehabilitation unit and subsequent discharge 5 months later, the patient recovered neurologically, with a return in his ability to walk, speak, and hear (Devoti et al, 2015).

a) Pulmonary edema has been reported (Hagebusch, 1937).

a) Tachypnea may occur secondary to acidosis (Okuonghae et al, 1992).

a) Drowsiness, headache, progressive obtundation and coma have preceded death (Calvery & Klumpp, 1939; O'Brien et al, 1998; Doyle et al, 1998; Wax, 1996).
b) CASE SERIES: Coma developed 3 to 5 days after severe poisoning with diethylene glycol in 7 fatal cases (Drut et al, 1994).
c) Drowsiness may be delayed approximately 24 hours after ingestion (Geiling & Cannon, 1938). Altered consciousness, as described by parents, developed in 17 of 86 (20%) children following ingestions of DEG-contaminated acetaminophen (O'Brien et al, 1998).
d) CASE REPORT: A 15-year-old girl was reported with a Glasgow coma scale score of 7 approximately 2 hr following the ingestion of 200 mL of brake fluid containing 55% triethylene glycol and 10% diethylene glycol. She was later admitted to ICU in stage II coma with bilateral clonus and severe agitation (Borron et al, 1997).

a) Severe neurological effects, consisting of encephalopathy, optic neuritis, fixed and dilated pupils, unilateral facial paralysis, respiratory failure, and coma, were reported in a case series of 109 children who ingested DEG-contaminated acetaminophen (O'Brien et al, 1998).
b) Delayed neurological effects, such as quadriparesis, sensorimotor peripheral neuropathy, fulminant ascending paralysis, demyelinating peripheral neuropathy, bulbar palsy, and sensorimotor polyneuropathy have been reported in some patients 10 to 47 days after exposure. It is suggested that the presence of severe metabolic acidemia with established renal failure on presentation may be predictive of subsequent delayed neurological toxicity (Reddy et al, 2010; Alfred et al, 2005; Hasbani et al, 2005).
c) Two weeks after ingesting diethylene glycol, three patients developed significant cranial neuropathies with bulbar palsy (Alfred et al, 2005).
d) CASE REPORT: A 40-year-old man presented with a 4-day history of nausea, general weakness, abdominal pain, diarrhea, and progressive oligo-anuria after the inadvertent ingestion of a colorless, sweet-tasting beverage containing diethylene glycol 5 days before presentation. Laboratory analysis revealed acute renal failure and anion-gap metabolic acidosis with normal osmolal gap. Urinalysis showed mild proteinuria (1.5 g/day) without crystalluria and a kidney biopsy showed acute and extensive tubular injuries, without intratubular oxalate crystals. He underwent intermittent hemodialysis, however, at this time, he developed a transient increase in liver and pancreatic enzymes. He also became lethargic on day 7, and he developed peripheral facial diplegia, and flaccid tetraparesis with an acute loss of visual acuity. Following supportive care, his condition gradually improved and he was able to walk 34 days after presentation. However, on follow-up 8 months later, complete peripheral facial diplegia and a slight impairment in renal function (serum creatinine 1.7 mg/dL) were noted (Morelle et al, 2010).
e) CASE SERIES: Encephalopathy, requiring ventilation, was reported in 11 children (ages ranging from 7 to 42 months) following ingestion of locally prepared antipyretic medications. The daily dose ranged from 15 to 30 mL. All 11 patients also experienced acute renal failure. Despite peritoneal dialysis and hemodialysis, 8 of the 11 patients died due to worsening encephalopathy. Neurologic sequelae was present in the 3 patients who survived and abnormal renal function without dialysis continued to persist in one patient. Further investigation of the antipyretic medications ingested by 6 of the 11 patients revealed that they contained acetaminophen and contaminated with diethylene glycol in amounts ranging from 2.3% to 22.3% (median 15.4% w/w) (Hari et al, 2006).
f) CASE REPORT: A 29-year-old man presented with nausea, abdominal pain, weakness, hypertension, and anuria. Laboratory results revealed severe renal failure (serum creatinine 15.5 mg/dL, estimated glomerular filtration rate (eGFR) 4.3 mL/min/1.73 m2), elevated transaminase concentrations, elevated serum lipase concentration, and metabolic acidosis. Interview of the patient's family revealed that he had been applying brake fluid, containing 10% diethylene glycol, to his skin for several months to treat a "dermatitis". Despite supportive therapy, including hemodialysis and continuous venovenous hemofiltration, the patient developed progressive drowsiness, hypotension, and respiratory failure necessitating intubation and mechanical ventilation. A renal biopsy was performed which indicated acute toxic proximal tubular necrosis without oxalate crystals. Over the next several days, the patient's neurologic status deteriorated with the development of ascending paralysis, areflexia, loss of corneal, vestibulo-ocular, and gag reflexes, and coma (Glasgow Coma Scale score of 3). With continued supportive care, the patient's neurologic and renal function gradually improved, with normalization of renal function parameters (serum creatinine of 1.26 mg/dL and eGFR 89 mL/min/1.73) approximately 33 days post-admission. Following transfer to a rehabilitation unit and subsequent discharge 5 months later, the patient recovered neurologically, with a return in his ability to walk, speak, and hear (Devoti et al, 2015).

a) Cerebral edema has been reported after severe diethylene glycol poisoning (Drut et al, 1994).

a) CASE SERIES: Paresthesias developed in several patients with fatal diethylene glycol poisoning. On autopsy these patients showed demyelination of peripheral nerves (Drut et al, 1994).
b) CASE REPORT: A 7-year-old child was reported to have evidence of CNS and peripheral demyelination after 5 days of anuria following ingestion of DEG adulterated acetaminophen (Scalzo A, 1996).
c) CASE REPORT: Following the ingestion of a solution containing diethylene glycol (28,000 mg/dL DEG [28%]; 2,500 mg/dL propylene glycol [2.5%]) and vodka, a 24-year-old man developed nausea, vomiting, abdominal pain, encephalopathy, and peripheral neuropathy. He developed progressive lethargy, facial diparesis, quadriparesis and areflexia, loss of corneal, vestibulo-ocular, and gag reflexes 5 days postingestion. Electrodiagnostic studies revealed absent left median, radial, and ulnar sensory responses and low-amplitude motor responses with preserved conduction velocity and minimally prolonged distal motor latencies. Studies during recovery period showed marked motor conduction velocity slowing and prolonged distal latencies. At the time of discharge, approximately 5 months postingestion, he could speak and had near-normal cognition with some memory deficits, moderate facial disparesis, residual mild distal weakness in both upper and lower extremities (4/5), absent reflexes, and length-dependent loss of pain, temperature, and vibration (Hasbani et al, 2005).
d) CASE REPORT: A 27-year-old man intentionally ingested 16 ounces of wallpaper stripper (26% DEG) and presented 24 hours later with nausea and vomiting, as well as an anion gap acidosis. Over the proceeding days, the patient developed renal failure, hepatocellular damage, and neurological deficits. An electromyography (EMG)/nerve conduction velocity (NCV) study showed sensorimotor peripheral neuropathy without demyelination. Methylprednisolone 500 mg was initiated, but the patient became quadriparetic necessitating intubation on day 12. Repeat EMG/NCV on day 56 showed severe demyelinating sensorimotor peripheral polyneuropathy. Despite supportive care, the patient continued to have diminished neurological function and was dialysis dependent 6 months following the ingestion (Marraffa et al, 2008).

a) Optic neuritis is a severe neurological manifestation of acute DEG poisoning (Morelle et al, 2010; O'Brien et al, 1998).
b) CASE REPORT: Mydriasis, optic neuritis and sixth nerve palsy, with sudden onset and evidence of demyelination, developed in a child several days following ingestion of DEG (Scalzo A, 1996).

a) Cerebral atrophy has been reported (Scalzo A, 1996).

a) CASE SERIES: Autopsy findings in 7 patients with severe diethylene glycol poisoning revealed hemorrhagic infarcts, subarachnoid hemorrhage, cerebral edema, and areas of demyelination (Drut et al, 1994).

a) Seizures may accompany severe cases of uremia/renal failure and have been reported in pediatric ingestions of DEG contaminated acetaminophen (Okuonghae et al, 1992; Wax, 1996).
b) CASE SERIES: Seizures occurred in 4 of 11 patients (36.4%) who ingested locally prepared antipyretic medications (daily doses ranging from 15 to 30 mL) containing acetaminophen and contaminated with diethylene glycol. The amount of diethylene glycol in the medications ranged from 2.3% to 22.3%. All 4 patients also developed acute renal failure and encephalopathy requiring ventilation (Hari et al, 2006).
c) CASE REPORT: One patient of three who ingested diethylene glycol developed agitation and a prolonged tonic-clonic seizure requiring sedation (Alfred et al, 2005).

a) CATTLE: Following oral exposures of 1.5 mL/kg, histopathologic findings included diffuse ganglioneuronal atrophy and perineuronal amphicytic hypertrophy of the Gasserian ganglion in cattle (Coppock et al, 1996).

a) CASE SERIES: Pancreatitis with diffuse fatty necrosis was reported at autopsy in 7 patients with acute diethylene glycol poisoning (Drut et al, 1994).
b) Increased serum amylase and lipase concentrations were reported in children following ingestion of DEG adulterated acetaminophen (Scalzo A, 1996). Pancreatitis was reported as a toxic effect in children, most of whom presented with renal failure, in a case series of children poisoned by ingestion of DEG-contaminated acetaminophen (O'Brien et al, 1998).
c) One man developed a transient increase in liver and pancreatic enzymes after ingesting a colorless, sweet-tasting beverage containing DEG (Morelle et al, 2010).
d) CASE REPORT: Increased serum lipase concentration (3,027 International Units/L; reference less than 216 International Units/L) occurred in a 29-year-old man who applied brake fluid, containing 10% diethylene glycol, to his skin for several months to treat a "dermatitis" (Devoti et al, 2015).

a) Common initial symptoms are nausea, abdominal cramps and vomiting (Devoti et al, 2015; Marraffa et al, 2008; Hasbani et al, 2005; Wax, 1996). Hematemesis may occur (Calvery & Klumpp, 1939). Heartburn is a common symptom (Geiling & Cannon, 1938). Diarrhea may occur (Geiling & Cannon, 1938; Okuonghae et al, 1992). Delayed onset (2 days) of abdominal pain and vomiting has been reported in 3 cases of ingestions of 2 to 3 cups of 100% DEG (Doyle et al, 1998).
b) Later symptoms include back pain and severe abdominal pain (Calvery & Klumpp, 1939).

a) Centrilobular necrosis presenting with slight jaundice and enlarged firm liver is a common finding (Geiling & Cannon, 1938).

a) Hepatomegaly was reported in a large number of fatal cases of children with renal failure following ingestions of DEG adulterated acetaminophen (Hanif et al, 1995; Okuonghae et al, 1992).

a) Elevated liver aminotransferases have been reported in cases of DEG adulterated acetaminophen ingestions (Scalzo A, 1996), after ingestion of DEG from other products (Morelle et al, 2010; Hasbani et al, 2005), and following dermal application, over several months, of brake fluid containing 10% DEG, to treat a "dermatitis" (Devoti et al, 2015).
b) Hepatitis was reported as a severe effect of DEG in children given DEG-contaminated acetaminophen (O'Brien et al, 1998).
c) Moderate elevations of aminotransferases have been reported in 3 fatalities following ingestions of 2 to 3 cups of 100% DEG as an ethanol substitute. Death was due to renal failure (Doyle et al, 1998).
d) CASE REPORT: A 27-year-old man intentionally ingested 16 ounces of wallpaper stripper (26% DEG) and presented 24 hours later with nausea and vomiting, as well as an anion gap acidosis. Over the proceeding days, the patient developed renal failure, neurological deficits, and hepatocellular damage. Treatment with N-acetylcysteine (NAC) was initiated on day 2, and hepatic transaminases peaked on day 4 of NAC therapy (AST 435 Units/L, ALT 1128 Units/L). Liver function tests normalized; however, despite supportive care, the patient continued to have diminished neurological function and was dialysis dependent 6 months following the ingestion (Marraffa et al, 2008).

a) CATTLE: were noted to have swollen friable liver with prominent lobular pattern at necropsy following oral exposures to 1.5 mL/kg. Histopathologic changes included centrilobular hydropic degeneration of hepatocytes (Coppock et al, 1996).

a) Acute renal failure may be a common finding in acute ingestions (O'Brien et al, 1998; Wax, 1996; Ferrari & Giannuzzi, 2005).
b) CASE REPORT: A 40-year-old man presented with a 4-day history of nausea, general weakness, abdominal pain, diarrhea, and progressive oligo-anuria after the inadvertent ingestion of a colorless, sweet-tasting beverage containing diethylene glycol 5 days before presentation. Laboratory analysis revealed acute renal failure and anion-gap metabolic acidosis with normal osmolal gap. Urinalysis showed mild proteinuria (1.5 g/day) without crystalluria and a kidney biopsy showed acute and extensive tubular injuries, without intratubular oxalate crystals. He underwent intermittent hemodialysis, however, at this time, he developed a transient increase in liver and pancreatic enzymes. He also became lethargic on day 7, and he developed peripheral facial diplegia, and flaccid tetraparesis with an acute loss of visual acuity. Following supportive care, his condition gradually improved and he was able to walk 34 days after presentation. However, on follow-up 8 months later, complete peripheral facial diplegia and a slight impairment in renal function (serum creatinine 1.7 mg/dL) were noted (Morelle et al, 2010).
c) Rentz et al (2008) evaluated 42 case patients with acute renal failure of unknown etiology and 140 control patients matched for age, gender and admission date. Mean serum creatinine was higher in case patients compared to controls (11.1 mg/dL versus 1.4 mg/dL). The authors found a significant association between the ingestion of prescription cough syrup and illness onset (95% CI 6.93 to 138), and analysis of the suspected cough syrup showed 8% DEG contamination of the syrup and 22% DEG contamination in the glycerin used in the cough syrup preparation (Rentz et al, 2008).
d) CASE SERIES: Sixty-four patients with liver disease were inadvertently exposed to DEG intravenously when administered DEG-contaminated (30%) armillarisin A injection. The daily exposed dose range was 3 to 6 mL, and the exposure course was 1 to 12 days. Fifteen patients developed acute renal failure, and 9 died within 2 weeks of exposure (Peng et al, 2009).
e) CASE SERIES: Hanif et al (1995) reported a major outbreak of fatal renal failure in children in Bangladesh between January 1990 and December 1992. A significant number of these children had ingested a brand of acetaminophen containing diethylene glycol (Hanif et al, 1995).
f) CASE SERIES: Acute renal insufficiency developed in 7 patients with fatal diethylene glycol poisoning (Drut et al, 1994).
g) CASE SERIES: Forty-seven children died from acute renal failure within 2 weeks of admissions to the emergency department following ingestions of DEG adulterated acetaminophen in Nigeria in 1990. Clinical findings on admission included: anuria, fever, vomiting, diarrhea, seizures, tachycardia, edema, hepatomegaly, hyperkalemia, acidosis, hypoglycemia, and increased serum creatinine (Okuonghae et al, 1992).
h) CASE SERIES: Scalzo (1996) reports children from Haiti presenting with profound renal failure and neurotoxic effects after ingesting DEG adulterated acetaminophen. One child had hydropic kidney swelling with less than 10% creatinine clearance (Scalzo, 1996).
i) CASE SERIES: Acute renal failure was reported in 11 children (ages ranging from 7 to 42 months) following ingestion of locally prepared antipyretic medications. The daily dose ranged from 15 to 30 mL. All 11 patients also experienced encephalopathy, requiring ventilation. Eight of the 11 patients died due to worsening encephalopathy. Abnormal renal function without dialysis continued to persist in one of the 3 patients who survived. Further investigation of the antipyretic medications ingested by 6 of the 11 patients revealed that they contained acetaminophen and contaminated with diethylene glycol in amounts ranging from 2.3% to 22.3% (median 15.4% w/w) (Hari et al, 2006).
j) CASE SERIES: O'Brien et al (1998) have identified 109 cases of anuric renal failure in children who had ingested DEG-contaminated acetaminophen. All of the children had either anuria or severe oliguria at hospital admission. Eleven of these children were lost to follow-up. Of the remainder, 88 out of 98 died, 7 recovered full renal function, and 1 child developed chronic renal failure (O'Brien et al, 1998).
k) CASE REPORTS: Doyle et al (1998) reported the delayed onset (6 days) of acute renal failure following the ingestion of 2 to 3 cups of 100% DEG in 3 previously healthy men. Despite peritoneal dialysis, all the men died between days 9 and 18 following the ingestions. The delayed presentation was considered a major contributing factor to the fatal outcomes (Doyle et al, 1998).
l) CASE REPORT: Following the ingestion of a solution containing diethylene glycol (28,000 mg/dL DEG [28%]; 2,500 mg/dL propylene glycol [2.5%]) and vodka, a 24-year-old man developed nausea, vomiting, abdominal pain, encephalopathy, and peripheral neuropathy. The laboratory tests showed an increased anion gap of 20 (normal <12), mild acidosis with bicarbonate concentration of 16 (22 to 30 mmol/L), creatinine concentration of 5.9 mg/dL (0.8 to 1.3 mg/dL), elevated aminotransferases, and elevated white blood cell count with left shift. He had hemodialysis on hospital day 3 after his oliguric renal failure worsened. Perinephric stranding, bilateral cortical necrosis and patent renal vessels were observed in abdominal imaging. Renal biopsy revealed hemorrhagic cortical necrosis with widespread arterial, arteriolar, and capillary fibrin thrombi without evidence of vasculitis or rapidly progressive glomerulonephritis (Hasbani et al, 2005).
m) Three patients developed severe acidemia (pH range 6.8 to 7.1 with elevated anion and osmolar gaps) and anuric acute renal failure requiring hemodialysis approximately 24 hours after the ingestion of diethylene glycol. All three patients remained hemodialysis-dependent. Renal biopsy of patient 1 revealed diffuse cortical necrosis. Renal biopsy of patient 2 revealed near total cortical necrosis (Alfred et al, 2005).
n) Death usually occurs 2 to 7 days after onset of anuria in untreated cases (Geiling & Cannon, 1938).
o) CASE REPORT: A 29-year-old man presented with nausea, abdominal pain, weakness, hypertension, and anuria. Laboratory results revealed severe renal failure (serum creatinine 15.5 mg/dL, estimated glomerular filtration rate (eGFR) 4.3 mL/min/1.73 m2), elevated transaminase concentrations, elevated serum lipase concentration, and metabolic acidosis. Interview of the patient's family revealed that he had been applying brake fluid, containing 10% diethylene glycol, to his skin for several months to treat a "dermatitis". Despite supportive therapy, including hemodialysis and continuous venovenous hemofiltration, the patient developed progressive drowsiness, hypotension, and respiratory failure necessitating intubation and mechanical ventilation. A renal biopsy was performed which indicated acute toxic proximal tubular necrosis without oxalate crystals. Over the next several days, the patient's neurologic status deteriorated with the development of ascending paralysis, areflexia, loss of corneal, vestibulo-ocular, and gag reflexes, and coma (Glasgow Coma Scale score of 3). With continued supportive care, the patient's neurologic and renal function gradually improved, with normalization of renal function parameters (serum creatinine of 1.26 mg/dL and eGFR 89 mL/min/1.73) approximately 33 days post-admission. Following transfer to a rehabilitation unit and subsequent discharge 5 months later, the patient recovered neurologically, with a return in his ability to walk, speak, and hear (Devoti et al, 2015).

a) RATS given doses greater than 10 mL/kg developed hydropic degeneration of the renal tubuli, non-compensated metabolic acidosis and uremic coma (Heilmair et al, 1993).
b) CATTLE: exposed to 1.5 mL/kg were noted to have enlarged friable kidneys and massive perirenal edema at necropsy. Histopathologic changes included proteinaceous casts in renal tubules and significant hydropic swelling of the renal tubular epithelium (Coppock et al, 1996).

a) Metabolic acidosis may occur, but is not as common as with ethylene glycol (Cantarell et al, 1987; Pandya, 1988).
b) Metabolic acidosis may accompany acute renal failure in DEG ingestions (Morelle et al, 2010; Hanif et al, 1995; Okuonghae et al, 1992; Ferrari & Giannuzzi, 2005) and following absorption after extensive dermal application of brake fluid, containing 10% diethylene glycol, to treat a "dermatitis" (Devoti et al, 2015).
c) Three patients developed severe acidemia (pH range 6.8 to 7.1 with elevated anion and osmolar gaps) and anuric acute renal failure requiring hemodialysis approximately 24 hours after ingesting varying quantities of diethylene glycol. All three patients remained hemodialysis-dependent. On the second week postingestion, they developed significant cranial neuropathies with bulbar palsy. Approximately 24 hours postingestion, two other patients presented to the emergency department with normal renal function and a moderate acidemia (pH range 7.2 to 7.28) requiring hemodialysis (Alfred et al, 2005).

a) CASE REPORT: Following the ingestion of 200 mL of brake fluid containing 55% triethylene glycol and 10% DEG, laboratory values in a 15-year-old girl were reported to be: plasma ethanol, 1 mmol/L; plasma lactate, 12 mmol/L; serum sodium, 139 mmol/L; serum potassium, 2.7 mmol/L; bicarbonate, 19 mmol/L; and anion gap, 27.7 mmol/L. Arterial blood gases were reported to be: pH, 7.34; pCO2, 3.99 kPa (29.9 mm Hg); pO2, 25.18 (188.9 mm Hg); HCO3, 15.8 mmol/L with FiO2, 0.5. The patient fully recovered following fomepizole (4-MP) therapy (Borron et al, 1997).
b) Three patients developed severe acidemia (pH range 6.8 to 7.1 with elevated anion and osmolar gaps) and anuric acute renal failure requiring hemodialysis approximately 24 hours after ingesting varying quantities of diethylene glycol. All three patients remained hemodialysis-dependent (Alfred et al, 2005).
c) CASE REPORT: Following the ingestion of a solution containing diethylene glycol (28,000 mg/dL DEG [28%]; 2,500 mg/dL propylene glycol [2.5%]) and vodka, a 24-year-old man developed nausea, vomiting, abdominal pain, encephalopathy, and peripheral neuropathy. The laboratory tests showed an increased anion gap of 20 (normal <12), mild acidosis with bicarbonate concentration of 16 (normal 22 to 30 mmol/L), creatinine concentration of 5.9 mg/dL (0.8 to 1.3 mg/dL), elevated aminotransferases, and elevated white blood cell count with left shift. He had hemodialysis on hospital day 3 after his oliguric renal failure worsened (Hasbani et al, 2005).
d) CASE REPORT: A 27-year-old man intentionally ingested 16 ounces of wallpaper stripper (26% DEG) and presented 24 hours later with nausea and vomiting. An increased anion gap of 20 (normal <12) and acidosis with bicarbonate concentration of 17 mmol/L (normal 22 to 30 mmol/L) were evident on initial laboratory results. The patient developed renal failure, hepatocellular damage and neurologic sequelae. Despite supportive care, the patient continued to have diminished neurological function and was dialysis dependent 6 months following the ingestion (Marraffa et al, 2008).

a) RATS: Doses of 1 and 5 mL/kg produced metabolic acidosis which was self- correcting. Doses greater than 10 mL/kg produced a non-compensated metabolic acidosis, degeneration of renal tubules, and uremic coma (Heilmair et al, 1993).

a) Leukocytosis is a common manifestation (Calvery & Klumpp, 1939; Hanif et al, 1995).

a) No significant skin irritation has been described.

a) Carbitols which are industrial solvents derived from diethylene glycol produced a case of diffuse erythematous dermatitis in a factory worker exposed chronically (Dawson et al, 1989).

a) Hypoglycemia has been reported in children following ingestions of DEG (Okuonghae et al, 1992).

a) MICE - Doses of 6.1 grams/kg/day produced decreased numbers of litters, pups per litter, and live births (Williams et al, 1990).

a) DETERMINATION OF OSMOLAL GAP: Difference between the measured serum osmolality (using freezing point depression) and the calculated osmolality (determined by the following equation: 2 x sodium (mmol/L) + glucose (mmol/L) + BUN (blood urea nitrogen) (mmol/L) + ethanol (mmol/L). Normal: less than 10 mOsm/L) (Schep et al, 2009).

a) Using the formula: Anion Gap = (Na - (Cl + HCO(3))): The range for a normal anion gap reported in some laboratories is 7 +/- 4 mmol/L (Hoffman et al, 1993; Schep et al, 2009).

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) An initial loading dose of 15 mg/kg is intravenously infused over 30 minutes followed by doses of 10 mg/kg/every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol concentrations are below 20 mg/dL (Prod Info ANTIZOL(R) IV injection, 2006).
b) HEMODIALYSIS: The frequency of dosing should be increased during dialysis. If dialysis is begun 6 hours or more since the last fomepizole dose the next scheduled dose should be administered. Dosing during dialysis should be increased to every 4 hours (Prod Info ANTIZOL(R) IV injection, 2006).

a) CONCENTRATIONS AVAILABLE (V/V)
b) PREPARATION OF 10% V/V ETHANOL IN A 5% DEXTROSE SOLUTION

a) HYPOGLYCEMIA
b) CONCURRENT ETHANOL
c) DISULFIRAM

a) INTRAVENOUS LOADING DOSE
b) ORAL LOADING DOSE

a) MAINTENANCE DOSE
b) MAINTENANCE DOSE/ETHANOL DIALYSATE
c) MAINTENANCE DOSE/ETHANOL-FREE DIALYSATE

a) There is very little information on ethanol dosing in the pediatric patient (Barceloux et al, 2002). The loading dose and maintenance infusion should be the same as for an adult non-drinker. Loading dose is 0.8 g/kg (8 mL/kg) of 10% ethanol infused over 1 hour, maintenance dose is 80 mg/kg/hr (0.8 mL/kg/hr) of 10% ethanol (Howland, 2011).
b) Blood ethanol concentration should be initially monitored hourly and the infusion rate should be adjusted to obtain an ethanol concentration of 100 to 150 mg/dL (Howland, 2011; Barceloux et al, 2002).

a) ETHANOL CONCENTRATION
b) ADDITIONAL MONITORING

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

1) Two days after intentional ingestion of two to three cups of 100% diethylene glycol, three men (ages 21 - 35) experienced vomiting and epigastric pain. They presented to the hospital six days after the ingestion with acute renal failure. All three patients died, despite peritoneal dialysis, between days 3 and 12 following admission (Doyle et al, 1998).
2) A 56-year-old man ingested 8 ounces of Sterno fluid (100% diethylene glycol) in an apparent suicide attempt. He developed confusion and acute kidney failure two days later, followed by ascending paralysis on day eight. Despite treatment with fomepizole and aggressive hemodialysis, he died 18 days after ingestion (Rollins et al, 2002).
3) The fatal cumulative dose of the "elixir of sulfanilamide" manufactured by Massengill in 1937 was estimated to be approximately 20 teaspoon fulls in adults (Wax, 1996), or 1 to 2 g/kg (Schep & Slaughter, 2005).
4) Seventy-one adults died after ingesting 20 to 240 milliliters (mean dose 99 milliliters) of diethylene glycol-containing sulfanilamide elixir (Laug et al, 1939; Calvery & Klumpp, 1939).
5) In a study of 15 victims of massive intoxication, the estimated lethal dose for humans ranged from 0.014 to 0.17 mg diethylene glycol/kg of body weight in patients who had ingested 20 mL of diethylene glycol syrup (Ferrari & Giannuzzi, 2005). However, Schep & Slaughter (2005) suggested that these estimated doses were incorrectly calculated and values that are described as mg dose per kg body weight are incorrect by a factor of 1000 (Schep & Slaughter, 2005).

1) In a case series, 85 (98%) of 87 children died following ingestion of diethylene glycol-contaminated paracetamol. The median estimated diethylene glycol dose ingested was 1.34 mL/kg (range of 0.22 to 4.42 mL/kg). An estimated maximum diethylene glycol dose less than 1.0 mL/kg was ingested by 12 children. Children ranged in age from 1 month to 13 years, with 80% of the children less than 5 years old (O'Brien et al, 1998).
2) Thirty-four children died after ingesting 5 to 120 milliliters (mean dose 53 milliliters) of diethylene glycol-containing sulfanilamide elixir (Laug et al, 1939; Calvery & Klumpp, 1939).
3) The fatal cumulative dose of the "elixir of sulfanilamide" manufactured by Massengill in 1937 was estimated to be approximately 10 teaspoon fulls in children (Wax, 1996), or 1 to 2 g/kg (Schep & Slaughter, 2005).
4) CASE SERIES: Acute renal failure and encephalopathy, requiring ventilation, was reported in 11 children (ages ranging from 7 to 42 months) following ingestion of locally prepared antipyretic medications. The daily dose ranged from 15 to 30 mL. Despite peritoneal dialysis and hemodialysis, 8 of the 11 patients died due to worsening encephalopathy. Neurologic sequelae was present in the 3 patients who survived and abnormal renal function without dialysis continued to persist in one patient. Further investigation of the antipyretic medications ingested by 6 of the 11 patients revealed that they contained acetaminophen and contaminated with diethylene glycol in amounts ranging from 2.3% to 22.3% (median 15.4% w/w) (Hari et al, 2006).

a) 9719 mg/kg -- chronic pulmonary edema; changes in kidney tubules and glomeruli; changes in spleen (RTECS, 2004)

a) 2300 mg/kg -- degenerative changes to the brain and coverings; liver changes; kidney, ureter, and bladder changes (RTECS, 2004)
b) 23,700 mg/kg -- general anesthetic effect; muscle weakness; liver changes (RTECS, 2004)
c) 26.5 g/kg (Bingham et al, 2001)

a) 7700 mg/kg (RTECS, 2004)

a) 12,000 mg/kg -- degenerative changes to the brain and coverings; liver changes; kidney, ureter, and bladder changes (RTECS, 2004)
b) 12,565 mg/kg (RTECS, 2004)
c) 15.6 g/kg (Bingham et al, 2001)
d) 16.6 g/kg (Bingham et al, 2001)
e) 20.8 g/kg (Bingham et al, 2001)

a) 18,800 mg/kg (RTECS, 2004)

a) 4 mg/m(3) for 2H/30W, intermittent -- carcinogenic; lymphomas, including Hodgkin's disease; tumors of the skin and/or appendages (RTECS, 2004)
b) 35 mg/m(3) for 11W, intermittent -- cardiac changes; fatty liver degeneration; death (RTECS, 2004)

a) 20 mg/m(3) for 2H/26W, intermittent -- lowered blood pressure; emphysema; death (RTECS, 2004)
b) 20 mg/m(3) for 4H/30D, intermittent -- somnolence (general depressed activity); degenerative changes to the brain and coverings (RTECS, 2004)
c) 35 mg/m(3) for 75D, intermittent -- changes in circulation (e.g., hemorrhage, thrombosis); liver changes; death (RTECS, 2004)