a) Bradypnea can occur (Goldfrank et al, 1994). Significant respiratory depression developed in 3 children following percutaneous exposure (Gimenez et al, 1968) and in a hypoglycemic, comatose child following ethanol ingestion (Ricci & Hoffman, 1982).

a) Tachypnea may develop as a compensatory mechanism in cases of ethanol-induced ketoacidosis (Goldfrank et al, 1994). Rapid, shallow, and noisy respirations with chest retractions occurred in a severely intoxicated child (Vogel et al, 1995). Aspiration of vomitus may have occurred.

a) Hypothermia is common (McGinnity de Laveaga & Caravati, 2015; Ruck et al, 2010; Lien & Mader, 1999; Wade & Gammon, 1999; Szpak et al, 1995; Selbst et al, 1985; Weyman et al, 1974; Moss, 1970). Combined exposure to ethanol and sedative-hypnotics can enhance vasodilation (Goldfrank et al, 1994) and increase hypothermia.
b) CASE REPORT: An 80-year-old man presented with a decreased level of consciousness 1 hour after intentionally ingesting 750 mL of vodka (40% ethanol by volume). Within 30 minutes of presentation, the patient became unresponsive, hypotensive, and hypothermic. Following supportive care, the patient gradually recovered without sequelae (Wilson & Waring, 2007). Prior alcohol abstinence by the patient may have contributed to the severity of symptoms.

a) Elevated body temperature has been reported in 3 pediatric cases of significant ethanol ingestion (Vogel et al, 1995; Hornfeldt, 1992).

a) Hypotension and bradycardia may occur (Ruck et al, 2010; Wilson & Waring, 2007; Lien & Mader, 1999; Goldfrank et al, 1994; Eilam & Heyman, 1991).

a) Tachycardia may be present (Ruck et al, 2010; Osborn, 1994).

a) Eye exposure to liquid generally causes transient pain, irritation, and reflex lid closure. A foreign-body sensation may persist for 1 to 2 days (Grant & Schuman, 1993). Vapors produce transient stinging and tearing but no apparent adverse effects (Grant & Schuman, 1993).

a) Transiently impaired color vision may occur with acute ingestion or chronic alcoholism. Abstinence from alcohol generally restores normal color vision in chronic alcoholics (Grant & Schuman, 1993).

a) Poor control of eye movements, with diplopia and nystagmus, may occur and alter vision and performance (Grant & Schuman, 1993). Acute overdoses of ethanol have caused spontaneous (not gaze-evoked) horizontal nystagmus (Anon, 1971). The greatest effects are on saccadic and smooth pursuit movements (Willoughby, 1987; Wilkinson et al, 1974).

a) Temporary blindness, with normal pupil reactivity and fundi, has been rarely associated with acute intoxication. Methanol ingestion was excluded (Walsh, 1957). Most cases of blindness reported in the earlier literature were caused by methanol and not by ethanol (Grant & Schuman, 1993).

a) Amblyopia due to peripheral neuritis has been reported in chronic alcoholics. Bilaterally decreased vision occurs. Vitamin deficiencies correlate with the ocular defects, and early administration of B vitamins causes recovery in some patients (Grant & Schuman, 1993).

a) Abnormal eye features, ptosis, strabismus, myopia, amblyopia, and optic disc pallor have been reported (Grant & Schuman, 1993; Galea & Goel, 1989).

a) Acute intoxication has been reported to result in non-pancreatic hyperamylasemia due to salivary isoamylase (Block et al, 1983).

a) An adult presented pulseless and apneic with a blood ethanol concentration of 1.127 g/dL. She was intubated, resuscitated, and treated with hemodialysis, and she recovered (Sanap & Chapman, 2003).
b) Cardiopulmonary arrest occurred in a 2-year-old who may have ingested 120 mL of tequila, 26.5% ethanol (Vogel et al, 1995).
c) Sudden death following acute intoxication have been reported in 6 cases, but the exact causes of death were not known, and preexisting medical conditions were present in some cases (Odesanmi, 1979).
d) Sudden death has occurred in patients with alcoholic cardiomyopathy who did not have angina or coronary artery disease (Sheehy, 1992).
e) CASE REPORT: A 36-year-old man, with a history of schizophrenia, presented to the emergency department (ED) with ethanol intoxication. The patient was uncooperative with slurred speech and nystagmus. A breath ethanol reading was 278 mg/dL. Four hours later, with supportive care, the patient was calm with a steady gait and was discharged. Thirty minutes later, the patient was found unresponsive and pulseless in the bathroom at the ED, with an empty 354-mL hand sanitizer containing 62% ethanol and less than 5% isopropanol. Following resuscitation, the patient developed spontaneous circulation with normal sinus rhythm, but never regained consciousness. His serum ethanol concentration was 526 mg/dL. A brain MRI showed extensive bilateral cortical infarction, cerebral edema, and sulcal effacement, indicating anoxic brain injury. The patient died on hospital day 7 following withdrawal of care. Based on his post-resuscitation serum ethanol concentration, it is suspected that the patient had ingested the majority of the contents of the hand sanitizer container (Schneir & Clark, 2013).

a) Acute alcohol intoxication may result in atrial fibrillation (Thorton, 1984; Ettinger et al, 1978). Precipitation of fibrillation was reported in a man who consumed 5.8 mg of denatured alcohol in a breath spray (Ridker et al, 1989).
b) CASE REPORT: A 16-year-old adolescent developed atrial fibrillation with a heart rate of 77 beats per minute approximately 1 hour following hospital admission for CNS depression secondary to consumption of an unknown amount of alcohol. The patient also complained of transient nonlocalizing chest pain. His chest x-ray was normal, and there was no evidence of hemodynamic instability. His blood alcohol level was 153.5 mg/dL. The patient was placed on heparin therapy, and his atrial fibrillation resolved 8 hours later as his blood alcohol level decreased. The patient was discharged without further sequelae (Koul et al, 2005).

a) Wenckebach-type AV block was reported in a 49-year-old comatose patient with a serum alcohol level of 536 mg/dL. Underlying organic heart disease and ingestion of other drugs were ruled out as potential causes (Eilam & Heyman, 1991).

a) A 71-year-old man with variant angina repeatedly developed chest pain after the consumption of moderate amounts of alcohol, but not after exercise. This patient had no history of hypertension or smoking. Myocardial ischemia was confirmed by ECG and thallium-201 exercise myocardial scintigrams (Ando et al, 1993).
b) Coronary artery spasm was induced approximately 9 hours after ingestion of 400 mL rice wine (17% ethanol) in 4 cases with histories of ethanol-induced variant angina and preexisting coronary artery stenosis. Blood ethanol levels were not elevated during the angina (Oda et al, 1994). Other human studies have also reported ethanol-induced angina (Miwa et al, 1994).

a) Acute intoxication may decrease cardiac output in persons with preexisting cardiac conditions (Osborn, 1994).

a) CASE REPORT (INFANT): A 15-day-old infant presented to the emergency department with flushed skin, hypoactive, and somnolent approximately 3 hours after drinking formula milk. At presentation, the patient was hypotensive (55/29 mmHg) and tachycardic (214 beats/min), and arterial blood gases indicated metabolic acidosis (pH 7.186, HCO3 16.7 mmol/L, pCO2 45.8 mmHg, base excess -10.1 mmol/L). The patient's serum ethanol concentration, obtained at admission, was 43 mg/dL. With supportive care, including IV fluid administration, the patient gradually recovered within 12 hours post-admission. An interview with the parents, 24 hours post-admission, revealed that the infant's formula had been inadvertently mixed with 10 mL of sake (Japanese wine prepared from fermented rice). Follow up of the patient over the next 12 months showed no evidence of psychomotor sequelae (Zaitsu et al, 2013).

a) EARLY EFFECTS/PRECLINICAL STAGE: Alcoholic cardiomyopathy has insidious onset and can be clinically inapparent (Kouvaras & Cokkinos, 1986). Symptoms of alcoholic cardiomyopathy are often present for an average of 10.5 months before diagnosis (Sheehy, 1992), but as many as 85% of cases have not been diagnosed through routine screening, unless angiography was performed (Bertolet et al, 1991).
b) LATER EFFECTS/CLINICAL STAGE: Findings may include (Estruch et al, 1993; Bertolet et al, 1991; Kouvaras & Cokkinos, 1986; Parker, 1974):
c) INCIDENCE/RISK FACTORS: Regular consumption of large amounts of alcohol for 5 or more years may lead to alcoholic cardiomyopathy in a small percentage of adults (1% out of 12%); some susceptible individuals may develop cardiomyopathy after doses as low as 3 ounces of strong alcoholic beverages daily for 10 years (Parker, 1974).

a) CASE REPORT: An acute myocardial infarction occurred in a 47-year-old man 6 hours after ingesting 0.5 liters of ethanol within 30 to 60 minutes (calculated plasma ethanol concentration was 2.36 g/kg). The patient recovered following treatment with aspirin, nitroglycerin infusion, and a streptokinase infusion. Three months later, a coronary angiography showed normal coronary arteries but marked hypokinesia of the left ventricular wall (Starc et al, 1999).

a) CASE REPORT: An 80-year-old man presented to the emergency department with a decreased level of consciousness 1 hour after intentionally ingesting 750 mL of vodka (40% ethanol by volume). Within 30 minutes following presentation, the patient became unresponsive, hypotensive (lowest mean arterial pressure 45 mmHg), and hypothermic (34.8 degrees C). Following supportive care, the patient gradually recovered without sequelae (Wilson & Waring, 2007). Prior alcohol abstinence by the patient may have contributed to the severity of symptoms.
b) CASE REPORT (INFANT): A 15-day-old infant presented to the emergency department with flushed skin, hypoactive, and somnolent approximately 3 hours after drinking formula milk. At presentation, the patient was hypotensive (55/29 mmHg) and tachycardic (214 beats/min), and arterial blood gases indicated metabolic acidosis (pH 7.186, HCO3 16.7 mmol/L, pCO2 45.8 mmHg, base excess -10.1 mmol/L). The patient's serum ethanol concentration, obtained at admission, was 43 mg/dL. With supportive care, including IV fluid administration, the patient gradually recovered within 12 hours post-admission. An interview with the parents, 24 hours post-admission, revealed that the infant's formula had been inadvertently mixed with 10 mL of sake (Japanese wine prepared from fermented rice). Follow up of the patient over the next 12 months showed no evidence of psychomotor sequelae (Zaitsu et al, 2013).
c) CASE REPORT/CHILD: A 3-year-old child presented to the emergency department with an altered mental status following suspected ingestion of a hand sanitizer containing 70% ethanol. Vital signs indicated a heart rate of 97 beats/minute and a blood pressure of 95/54 mmHg. Her Glasgow Coma Scale score was 10. Within an hour of presentation, she became hypotensive (70/22 mmHg). Her serum ethanol concentration was 260 mg/dL. Following administration of IV fluids and epinephrine, and continued observation, the patient gradually recovered and was discharged within 24 hours of presentation (Barrett & Babl, 2015).
d) CASE REPORT (CHILD): A 3-year-old child with cerebral palsy was found cold, pale, and unresponsive (Glasgow Coma score of 3) by emergency personnel and presented to the emergency department with hypotension (56/25 mmHg), tachycardia (130 beats/min) and hypothermia (33.9 degrees C), with pinpoint pupils. Arterial blood gas analysis revealed lactic acidosis (pH 7.15, pCO2 43, HCO3 14.3 mmol/L, lactate 5.3 mmol/L). Serum ethanol concentration was 958 mg/dL. Despite supportive care, the patient's hypotension (65/48 mmHg) and acidosis persisted. Hemodialysis was performed approximately 5 hours post-presentation for a period of 4 hours. Immediately following hemodialysis, the patient's serum ethanol concentration decreased to 70 mg/dL. Her blood pressure stabilized, the acidosis resolved, and she became increasingly responsive (McGinnity de Laveaga & Caravati, 2015).

a) Ethanol plus cocaine injected IV in anesthetized dogs synergistically depressed left ventricular contraction, left ventricular relaxation, and stroke volume but increased heart rate and mean pulmonary arterial pressure. Oxygen saturation of the venous blood was also significantly decreased by the combined treatments. Ethanol alone did not significantly alter mean arterial pressure, ventricular relaxation, ventricular contraction, heart rate, or mixed venous blood oxygen saturation (Henning et al, 1994).
b) Other studies have reported additive depression of the left ventricular ejection fraction in dogs following IV ethanol and cocaine (Uszenski et al, 1992).

a) Respiratory depression has been reported in substantial ingestions (Johnstone & Witt, 1972)(Johnstone & Reier, 1973) and in 3 pediatric cases of dermal exposure (Gimenez et al, 1968). Death due to respiratory failure can occur after significant ingestions (Osborn, 1994).
b) INCIDENCE: A prospective observational study was conducted to determine the incidence of hypoventilation in adolescents with acute alcohol intoxication, as well as determine if there is a correlation between alcohol concentrations and the incidence of hypoventilation. The study included 65 patients, ages ranging from 14 to 19 years old. Hypoventilation episodes, measured via capnography, occurred in 28% of the patients, with the majority of episodes (92%) identified as hypopneic hypoventilation (end-title carbon dioxide [ETCO2] of 30 mmHg or less). There were also 2 episodes of apnea (ETCO2 of 0 mmHg) and 2 episodes of bradypneic hypoventilation (an ETCO2 of at least 50 mmHg). There was no significant difference in the mean alcohol concentration between the patients who experienced hypoventilation (186 mg/dL; n=18), and the patients who did not experience hypoventilation (185 mg/dL; n=47). There was also no significant difference in the number of hypoventilation episodes that occurred on arrival to the hospital and during the first 5 hours of capnographic measurements. No episodes were recorded after the fifth hour of monitoring (Langhan, 2013).

a) Cheyne-Stokes respirations may be present in comatose cases (Cummins, 1961).

a) Dyspnea, which may progress to Kussmaul respirations (deep and sighing respirations with variable rate), may be present in cases of alcohol-induced ketoacidosis (Larremore, 1984; Edwards & Hoyt, 1973; Jenkins et al, 1971).

a) Aspiration of vomitus may occur, resulting in pneumonitis and pulmonary edema (Johnson, 1985; Dickerman et al, 1968).

a) Vapors may cause coughing and transient irritation of the upper respiratory tract (American Conference of Governmental Industrial Hygienists, 2010).

a) Exacerbation of asthma has been reported after ingestion of ethanol and exposure to ethanol vapors (Ayres, 1997; Zellweger, 1997).

a) Moderate ethanol intoxication (1 mg/kg of ethanol as a 45% aqueous solution) reduces peripheral oxygen delivery and metabolism and causes mitochondrial oxidative dysfunction, possibly resulting in shock or hypoxia in the acutely intoxicated patient (Gutierrez et al, 1999).

a) HAND SANITIZERS: In a retrospective review of 647 pediatric (age range, 1 month to 5 years; mean age, 1.89 years) exposures to ethanol-based hand sanitizers (599 ingestions, 105 dermal, 29 ocular, and 2 inhalational), cough developed in 4 patients (Mrvos & Krenzelok, 2009).

a) CNS depression can be profound and may lead to death. Lethal blood levels range from 260 mg% to greater than 700 mg%. Alcoholics tolerate higher levels than abstainers, who tolerate higher levels than children. Coingestion of sedative hypnotics or tranquilizers may be lethal with relatively low blood ethanol levels.
b) Loss of consciousness has been reported in teenagers intoxicated by Cisco, a carbonated, fortified wine that has an alcohol content of 20%. Average blood alcohol levels in 16 cases were about 200 mg/dL (AAPCC, 1991).
c) CNS depression (Glasgow Coma Scale [GCS] of 11), disorientation, incoherence, and ataxia were reported in a 16-year-old adolescent following consumption of an unknown amount of alcohol. His blood alcohol level was 153.5 mg/dL (Koul et al, 2005).
d) CASE REPORT: An 80-year-old man presented to the emergency department with a decreased level of consciousness 1 hour after intentionally ingesting 750 mL of vodka (40% ethanol by volume). Within 30 minutes following presentation, the patient became unresponsive, hypotensive, and hypothermic. Following supportive care, the patient gradually recovered without sequelae (Wilson & Waring, 2007). Prior alcohol abstinence by the patient may have contributed to the severity of symptoms.
e) CASE REPORT (PEDIATRIC): A 3-year-old child presented to the emergency department with a loss of balance, vomiting, drowsiness, and unresponsiveness to painful stimuli following a suspected ingestion of an alcohol-based hand sanitizer, containing 62% ethanol. In addition, the patient also developed nystagmus, mydriasis, hypotension (108/56 mmHg), tachycardia (108 bpm), and hypothermia (94.7 degrees F). An initial blood ethanol level, obtained approximately 1 hour post-presentation, was 212 mg/dL. With supportive care, the patient's condition improved with a decrease in her blood ethanol level to 45 mg/dL, 6 hours after the first level, and undetectable 8 hours later (Ruck et al, 2010). In order for the patient to initially present with a blood ethanol level of 212 mg/dL, it is believed that she ingested approximately 45 mL of the hand sanitizer.
f) CASE REPORT (INFANT): A 15-day-old infant presented to the emergency department with flushed skin, hypoactive, and somnolent approximately 3 hours after drinking formula milk. At presentation, the patient was hypotensive (55/29 mmHg) and tachycardic (214 beats/min), and arterial blood gases indicated metabolic acidosis (pH 7.186, HCO3 16.7 mmol/L, pCO2 45.8 mmHg, base excess -10.1 mmol/L). The patient's serum ethanol concentration, obtained at admission, was 43 mg/dL. With supportive care, including IV fluid administration, the patient gradually recovered within 12 hours post-admission. An interview with the parents, 24 hours post-admission, revealed that the infant's formula had been inadvertently mixed with 10 mL of sake (Japanese wine prepared from fermented rice). Follow up of the patient over the next 12 months showed no evidence of psychomotor sequelae (Zaitsu et al, 2013).
g) CASE REPORT (INFANT): A 9-week-old infant presented to the emergency department acting "strangely" and smelling of alcohol. Examination of the infant revealed decreased mental status and vital signs indicated an increased heart rate (160 beats/minute) and respirations (22 breaths/minute). Interview of the family revealed that the grandmother had inadvertently prepared the child's formula with 90 mL of vodka instead of water. The patient's blood glucose concentration, obtained by fingerstick at admission and at 1 hour and 3 hours postadmission, was 167 mg/dL, 160 mg/dL, and 98 mg/dL, respectively. His serum blood alcohol level, obtained at presentation, was 330 mg/dL. Three hours and 24 hours later, the blood alcohol level decreased to 0.27 mg/dL and less than 0.01 mg/dL, respectively. Following IV administration of 5% dextrose with normal saline (D5NS), the patient recovered and was discharged to home approximately 24 hours postadmission (Minera & Robinson, 2014).
h) CASE REPORT (CHILD): A 3-year-old child presented to the emergency department with altered mental status following suspected ingestion of a hand sanitizer containing 70% ethanol. Vital signs indicated a heart rate of 97 beats/minute and a blood pressure of 95/54 mmHg. Her Glasgow Coma Scale score was 10. Within an hour of presentation, she became hypotensive (70/22 mmHg). Her serum ethanol concentration was 260 mg/dL. Following administration of IV fluids and epinephrine, and continued observation, the patient gradually recovered and was discharged within 24 hours of presentation (Barrett & Babl, 2015).
i) CASE REPORT (ADOLESCENT): A 14-year-old boy presented to the emergency department with an altered mental status and an inability to walk on his own. Examination of the patient demonstrated a Glasgow Coma score of 6 and an absence of a gag reflex, necessitating intubation. Arterial blood gas analysis revealed metabolic acidosis, and laboratory data revealed a serum ethanol concentration of 233 mg/dL. Other toxicologic screening was negative for drugs of abuse and acetaminophen level was normal. Following supportive care, he was extubated and referred to psychiatry for consultation. Interview of the patient's friends indicated that he had ingested 24 ounces of lemon cooking extract. It was determined that lemon extract has a similar alcohol content as bourbon and absinthe (Dayton et al, 2015).

a) Coma has been reported in children (McGinnity de Laveaga & Caravati, 2015; Hornfeldt, 1992; Cummins, 1961).
b) CASE REPORT (ADULT): A 38-year-old hospitalized man with a history of alcohol abuse was found collapsed on a bathroom floor of a general medical ward. Neurologic assessment in the emergency department showed that he was comatose with a GCS of 3, necessitating intubation. His blood alcohol level was greater than 500 mg/dL. Approximately 90 minutes later, the patient regained consciousness and was extubated. It was later determined that he had consumed an unknown amount of hand-wash gel containing 70% alcohol in glycerol (Roberts et al, 2005).
c) CASE REPORT (ADULT): A 52-year-old woman presented to the emergency department comatose, apneic, and hypothermic after consuming 1 liter of methylated spirits (consisting of 95% ethanol and small amounts of fluorescein, denatonium benzoate, and methyl isobutyl ketone). Her initial blood ethanol level was 1.127 g/dL (245 mmol/L). Following early resuscitation and dialysis, the patient's clinical status improved, and she was discharged approximately 8 days post-admission without neurologic sequelae (Sanap & Chapman, 2003).
d) CASE REPORT (PEDIATRIC): Coma (GCS of 3) occurred in a 3-year-old boy following ingestion of an ethanol-containing mouthwash. The patient was awake and alert 30 minutes after receiving supportive treatment (Wade & Gammon, 1999).
e) CASE REPORT (PEDIATRIC): A 3-year-old child presented to the emergency department in a comatose state after ingesting an unknown amount of alcohol-based hand sanitizer, containing 65% ethanol. An initial blood ethanol level was 164 mg/dL. With supportive care, the patient's mental status improved, and a repeat blood ethanol level, obtained 2 hours later, was 127 mg/dL. The patient's condition returned to baseline the following day and she was discharged (Thomas et al, 2010).

a) Seizures have occurred in children secondary to hypoglycemia following dermal exposure or ingestion (Hornfeldt, 1992; Leung, 1986; Selbst et al, 1985; Gimenez et al, 1968; Cummins, 1961).

a) Children may experience severe lethargy and hypotonia after acute exposure (Da Dalt et al, 1991; Ricci & Hoffman, 1982; Weller-Fahy et al, 1980).
b) CASE REPORT (INFANT): A 1-month-old child whose ethanol level was 362 mg% was severely hypotonic and lethargic after home treatment with dermal ethanol soaks for 3 days. With supportive treatment and removal of the ethanol-impregnated wraps, her mental status improved to normal within 18 hours (Da Dalt et al, 1991).
c) CASE REPORT (PEDIATRIC): A 33-month-old child was stuporous 2 hours after possibly ingesting 11 ounces of mouthwash (48.2 g of absolute ethanol). Blood ethanol level was 306 mg% 3.5 hours after ingestion. Treatment included normal saline nasogastric lavage, warming by radiant heater, IV fluids, and bicarbonate. Eight hours postingestion, the blood ethanol level was 128 mg%. Recovery occurred by 18 hours after admission (Weller-Fahy et al, 1980).
d) CASE REPORT (PEDIATRIC): A 4-year-old child became "floppy" but responsive after ingesting approximately 6 ounces of an ethanol-based liquid hand sanitizer. The patient' blood ethanol level, obtained approximately 60 to 90 minutes post-ingestion, was 221 mg/dL. The patient recovered with supportive care (Reed et al, 2010).
e) CASE REPORT (INFANT): A 29-day old 3.5 kg infant was brought to the emergency department because of suspected ethanol intoxication due to reported ingestion of soy formula that was mixed with 1 to 3 ounces of gin instead of water. At presentation, approximately 1.5 hours post-ingestion, the patient had a weak cry and cough, with a variable tone, described as "flat", "floppy", and "normal". Her initial heart rate was 181 beats/min, blood pressure of 85/67 mmHg and respiratory rate of 47 breaths/min; oxygenation was normal on room air. Physical examination was normal. Laboratory data revealed an initial blood alcohol concentration, obtained approximately 2 hours post-ethanol ingestion, was 301 mg/dL. All other laboratory parameters, including serum electrolytes, renal function tests, and glucose were within normal limits. With supportive care, including continuous administration of IV fluids containing 5% dextrose and 0.45% sodium chloride at 6 mL/kg/hour, the patient was awake and alert, and feeding normally. Continued observation revealed a slight increase in a liver enzyme level (AST 87 units/L) approximately 13 hours post ethanol-ingestion, but resolved 12 hours later. All other cardiovascular, neurologic, respiratory, and glycemic parameters remained normal, and the patient was discharged 3 days post-admission (Fong & Muller, 2014).

a) Blood levels below 50 mg% (11 mmol/L) rarely lead to marked sensory or motor impairment. Values above 150 mg% (32.6 mmol/L) may cause ataxia and are consistent with intoxication (Koul et al, 2005; Goldfrank et al, 1998).
b) Ataxia may be an indication of alcoholic cerebellar degeneration (Juntunen, 1982).
c) CASE REPORT (PEDIATRIC): A 4-year-old child was unable to walk and had slurred speech after ingesting an unknown amount of an alcohol-based liquid hand sanitizer. The patient's blood ethanol level, obtained approximately 1 hour post-ingestion, was 200 mg/dL. With supportive therapy and overnight observation, the patient recovered and was discharged (Reed et al, 2010).

a) Reflexes may be normal, absent, decreased, or increased (Ricci & Hoffman, 1982; Gimenez et al, 1968).

a) Doll's eyes have been reported in children (Vogel et al, 1995; Ricci & Hoffman, 1982).

a) CHRONIC ABUSE: Peripheral neuropathy has been reported in alcoholics (Juntunen, 1982). In one study, alcoholics reported more symptoms consistent with peripheral neuropathy than controls, but electrophysiological testing did not confirm peripheral neuropathy in most of these alcoholics (Estruch et al, 1993).

a) DRIVING IMPAIRMENT: Deterioration of driving skills occurs at blood ethanol levels of 100 mg% and becomes progressively more serious as the level increases (Goldfrank et al, 1998).
b) The probability of causing an accident is related to the blood ethanol level (Council on Scientific Affairs, 1986).

                                Approximate
     Blood Ethanol Level     Crash Probability
           40 mg%                   1%
          100 mg%                   7%
          140 mg%                  20%
          160 mg%                  35%

c) CASE REPORT/IMPAIRED OBJECTIVE PERFORMANCE: A randomized, double-blind, placebo-controlled, 4-way crossover study using 20 healthy male volunteers showed impairment of psychomotor function (Gengo et al, 1990). Changes in objective performance test scores were well correlated with the estimated blood alcohol concentration.

a) Wernicke-Korsakoff syndrome (a more severe deficit in learning and memory) and dementia have been reported in alcoholics (Zubaran et al, 1997; Filley & Kelly, 1993).
b) One study examined a population-based sample of 554 subjects (from a prospective Finnish twin cohort study; 65 years or older at the time of demential assessment) to determine the long-term effects of midlife alcohol use on cognitive performance later in life. At the end of the follow-up period (25 years), 103 individuals had developed dementia. Midlife alcohol binge drinking (5 bottles of beer or a bottle of wine) at least once per month was associated with a relative risk of 3.2 (95% CI, 1.2 to 8.6) for dementia. Passing out following excessive alcohol use at least twice during the previous year was associated with a relative risk of 10.5 (2.4 to 46) for dementia. The authors concluded that binge drinking in midlife is associated with an increased risk of dementia and cognitive decline later in life (Jarvenpaa et al, 2005).

a) Blackout spells may occur, particularly with frequent ingestion of large volumes of ethanol. These amnesia episodes affect specific memories and are not associated with loss of consciousness. The person is unable to recall events of several hours and may not appear intoxicated. Patients do not have long-term memory impairment of immediate recall (Jennison & Johnson, 1994; Myerson & Rubin, 1992).
b) Blackouts can be eliminated if ethanol intake is significantly reduced (Jennison & Johnson, 1994).
c) Memory in alcoholics may improve with prolonged abstinence. Abstinence of an average of 7 years was associated with normal learning and memory scores; deficits were present in alcoholics who had abstained for only an average of 30 days or 2 years (Reed et al, 1982).

a) Auditory and/or visual hallucinations may occur in chronic ethanol abusers (Tsuang et al, 1994).

a) Although the subject of some professional dispute, some data indicate that a small number of people may be exceptionally sensitive to ethanol, exhibiting combative and irrational behavior after ingesting nonintoxicating amounts. This has been termed pathological intoxication or ethanol idiosyncratic intoxication (Perr, 1986).

a) CNS EFFECTS OF VAPOR INHALATION: Dose-related (1000 to 5000 parts per million) effects include headache, fatigue, and stupor (American Conference of Governmental Industrial Hygienists, 2010).

a) RATS: Long-term dietary ethanol resulted in loss of hippocampal neurons in the rat brain (Paula-Barbosa et al, 1993).

a) Nausea, vomiting, abdominal pain, and gastrointestinal bleeding often occur (Fields et al, 1994; Watson et al, 1974).
b) HAND SANITIZERS: In a retrospective review of 647 pediatric (age range, 1 month to 5 years; mean age, 1.89 years) exposures to ethanol-based hand sanitizers (599 ingestions, 105 dermal, 29 ocular, and 2 inhalational), oral irritation and vomiting were reported in 2 and 5 patients, respectively (Mrvos & Krenzelok, 2009).

a) Diarrhea has been reported in children following dermal exposure (Gimenez et al, 1968) and in adults who had normal pancreatic function (Fields et al, 1994; Estruch et al, 1993).

a) CHRONIC ethanol abuse is a common cause of acute and chronic pancreatitis with both endocrine and exocrine insufficiency (Singh & Simsek, 1990).
b) Acute pancreatitis or pancreatic fibrosis can result from chronic alcohol consumption (Edwards & Hoyt, 1973; Jenkins et al, 1971). Symptoms include nausea, vomiting, and abdominal pain, often radiating to the back (Myerson & Rubin, 1992).

a) Inflammation and hemorrhage developed in a case following a 140 mL enema containing 95% ethanol (Triantafillidis et al, 1994).

a) Esophageal varices that may cause fatal hemorrhage have been reported in alcoholics with cirrhosis and portal hypertension (Kartsonis et al, 1986; Dagradi, 1973).

a) CASE REPORT: Oral mucosal ulcerations were reported following misuse of an undiluted OTC mouthwash containing 70% ethanol. An intraoral exam showed an erythematous oral mucosa with necrotic areas and linear clefts resembling bullae. The patient recovered following topical application of a mixture containing diphenhydramine, Maalox(R), and 2% viscous lidocaine (Moghadam et al, 1999).

a) ACUTE EFFECTS: Ethanol can cause acute hepatitis, characterized by an enlarged and tender liver (Myerson & Rubin, 1992).

a) CHRONIC EFFECTS: Chronic, excessive ethanol use can cause hepatomegaly, hepatic fibrosis, steatosis, necrosis, cirrhosis, chronic hepatocellular failure, elevated serum aminotransferase, and elevated gamma-glutamyltransferase (Estruch et al, 1993; Flannery et al, 1991; Richardson et al, 1991). Patients with cirrhosis may be asymptomatic (Estruch et al, 1993).
b) ACETAMINOPHEN: Hepatotoxicity was associated with recent ethanol use in 8 out of 8 cases (7 out of 8 were chronic ethanol users) who had ingested more than 10 g/day acetaminophen, doses above the recommended acetaminophen limit of 4 g/day (Whitcomb & Block, 1994). Five out of 8 cases were also fasting, a risk factor associated with significant hepatotoxicity after acetaminophen doses, which generally cause minimal hepatotoxicity (4 to 10 g/day acetaminophen).
c) Chronic ethanol use interferes with storage of glycogen and causes depletion of vitamin A (Lieber & DeCarli, 1991; Dukes, 1981).

a) Cocaine-induced hepatotoxicity was increased by chronic ethanol treatment in a murine model (Odeleye et al, 1993).
b) ACUTE ethanol administration inhibited hepatic metabolism (biotransformation) of pentobarbital in rats and meprobamate in rat liver slices, and inhibited hepatic aniline hydroxylase, pentobarbital hydroxylase, aminopyrine, and ethylmorphine demethylase activities in vitro (Rubin et al, 1970).
c) CHRONIC ethanol exposure potentiated carbon tetrachloride-associated hepatotoxicity, effects on hepatic drug metabolizing enzymes (decreased total cytochrome P450 and aminopyrine N-demethylase activities) in vivo, and increased biotransformation of carbon tetrachloride in vitro (Hasumura et al, 1974).

a) Two patients developed acute renal failure associated with the combination of "binge" drinking and chronic ingestion of NSAIDS (Calvino et al, 2013).

a) Lactic acidosis has been reported in children (Leung, 1986; Selbst et al, 1985) and in alcoholics (Lien & Mader, 1999; Braden et al, 1993) after acute ingestions.
b) Acute lactic acidosis can produce a number of nonspecific effects, including fatigue, confusion, stupor, respiratory collapse, shock, and coma (Myerson & Rubin, 1992).
c) Lactic acidosis occurred in an alcoholic 10 hours after discontinuing ethanol (Flannery et al, 1991).
d) CASE REPORT (CHILD): A 3-year-old child with cerebral palsy was found cold, pale, and unresponsive (Glasgow Coma score of 3) by emergency personnel and presented to the emergency department with hypotension (56/25 mmHg), tachycardia (130 beats/min) and hypothermia (33.9 degrees C), with pinpoint pupils. Arterial blood gas analysis revealed lactic acidosis (pH 7.15, pCO2 43, HCO3 14.3 mmol/L, lactate 5.3 mmol/L). Serum ethanol concentration was 958 mg/dL. Despite supportive care, the patient's hypotension (65/48 mmHg) and acidosis persisted. Hemodialysis was performed approximately 5 hours post-presentation for a period of 4 hours. Immediately following hemodialysis, the patient's serum ethanol concentration decreased to 70 mg/dL. Her blood pressure stabilized, the acidosis resolved, and she became increasingly responsive (McGinnity de Laveaga & Caravati, 2015).
e) CASE REPORT: A 59-year-old man with a history of type 2 diabetes mellitus, presented with agitation and lower back pain after ingesting ethanol in combination with a laminate floor cleaner. Prior to presentation, the patient had been abusing ethanol for several weeks and had not been taking his insulin and metformin during this period. His glucose level was 23.8 mM (reference range, 3.5 to 7.1 mM), blood gas analysis revealed severe metabolic acidosis with an elevated anion gap and a lactate level of 22 mM (reference range, 0.5 to 2.2 mM), and a urinalysis was positive for ketones, indicating diabetic ketoacidosis. At admission, his blood ethanol level was 1 mg/mL; however, it was estimated that his peak blood alcohol level 8 hours prior to presentation, following his reported ethanol and laminate floor cleaner ingestion, was at least 2.4 mg/mL. With supportive care, he gradually recovered with normalization of his blood glucose and lactate levels (Hendrikx et al, 2014).

a) A prospective study was conducted to determine the association between ethanol intoxication and the development of acidosis. The study enrolled 192 patients, of which 147 were classified as nonintoxicated and 45 were classified as ethanol-intoxicated, with a mean blood alcohol level (BAL) of 205 +/- 81 mg/dL. The results of this study showed that there was a statistically significant difference in the prevalence of metabolic acidosis in ethanol-intoxicated patients (42%) compared with the nonintoxicated group (1%). The ethanol-intoxicated group had a lower arterial base deficit (BD) (mean difference: 2.19 mmol/L; 95% CI, 1.37 to 3.01 mmol/L) and a higher lactate level (LAC) (mean difference: 0.69 mmol/L; 95% CI, 0.11 to 1.27 mmol/L). However, there did not appear to be any significant correlation between the BD or LAC and the serum ethanol level in the ethanol-intoxicated patients, indicating that the degree of acidosis cannot be predicted by the serum ethanol level; thus severe metabolic or lactic acidosis cannot be completely attributed to ethanol consumption (Zehtabchi et al, 2005).
b) CASE REPORT (INFANT): A 15-day-old infant presented to the emergency department with flushed skin, hypoactive, and somnolent approximately 3 hours after drinking formula milk. At presentation, the patient was hypotensive (55/29 mmHg) and tachycardic (214 beats/min), and arterial blood gases indicated metabolic acidosis (pH 7.186, HCO3 16.7 mmol/L, pCO2 45.8 mmHg, base excess -10.1 mmol/L). The patient's serum ethanol concentration, obtained at admission, was 43 mg/dL. With supportive care, including IV fluid administration, the patient gradually recovered within 12 hours post-admission. An interview with the parents, 24 hours post-admission, revealed that the infant's formula had been inadvertently mixed with 10 mL of sake (Japanese wine prepared from fermented rice). Follow up of the patient over the next 12 months showed no evidence of psychomotor sequelae (Zaitsu et al, 2013).

a) Ketoacidosis may be present, particularly following an ethanol binge in patients with a history of chronic ethanol abuse and malnutrition (Larremore, 1984). An anion-gap metabolic acidosis, ketonemia, or ketonuria and normal, elevated, or low serum glucose may be present (Wade & Gammon, 1999; Braden et al, 1993; Edwards & Hoyt, 1973; Jenkins et al, 1971).
b) CASE REPORT: A 59-year-old man with a history of type 2 diabetes mellitus, presented with agitation and lower back pain after ingesting ethanol in combination with a laminate floor cleaner. Prior to presentation, the patient had been abusing ethanol for several weeks and had not been taking his insulin and metformin during this period. His glucose level was 23.8 mM (reference range, 3.5 to 7.1 mM), blood gas analysis revealed severe metabolic acidosis with an elevated anion gap and a lactate level of 22 mM (reference range, 0.5 to 2.2 mM), and a urinalysis was positive for ketones, indicating diabetic ketoacidosis. At admission, his blood ethanol level was 1 mg/mL; however, it was estimated that his peak blood alcohol level 8 hours prior to presentation, following his reported ethanol and laminate floor cleaner ingestion, was at least 2.4 mg/mL. With supportive care, he gradually recovered with normalization of his blood glucose and lactate levels (Hendrikx et al, 2014).

a) Anemia is associated with chronic, excessive ethanol use (Nakao et al, 1991; Bottiger, 1973; Edwards & Hoyt, 1973; Bauer & Strass, 1972).

a) Transient thrombocytopenia is common in alcoholics (Nakao et al, 1991; Bottiger, 1973).

a) Severe pancytopenia and bone marrow hypoplasia developed 1 month after an adult with a 7-year history of excessive ethanol use greatly increased his daily ethanol intake. Abstinence resulted in improved hematopoiesis, but thrombocytopenia and bone marrow hypoplasia developed with resumed ethanol use (Nakao et al, 1991).

a) Mild leukopenia is common in chronic alcoholics (Osborn, 1994).

a) Prolonged PT, PTT, and INR are common in patients with significant alcoholic cirrhosis (Osborn, 1994).

a) RATS: Significant decreases in red blood cell count, white blood cell count, hemoglobin, and hematocrit, but significant increases in mean cell volume, erythrocyte sedimentation rate, and neutrophil count occurred in rats after chronic, high-dose ethanol ingestion (Kanwar & Tikoo, 1992).

a) PERCUTANEOUS ABSORPTION: Pediatric cases indicate that ethanol can be absorbed through the skin, particularly if the skin is damaged, resulting in significant toxicity (Da Dalt et al, 1991; Puschel, 1981; Moss, 1970; Gimenez et al, 1968).

a) Facial flushing may occur. Ingestion of ethanol and exposure to solvents (eg, trichloroethylene, carbon disulfide, formamide) can result in flushing of the face, arms, and chest; this is sometimes called degreaser's flush (Cox & Mustchin, 1991).
b) CASE REPORT (INFANT): A 15-day-old infant presented to the emergency department with flushed skin over her entire body, hypoactive, and somnolent approximately 3 hours after drinking formula milk. At presentation, the patient was hypotensive (55/29 mmHg) and tachycardic (214 beats/min), and arterial blood gases indicated metabolic acidosis (pH 7.186, HCO3 16.7 mmol/L, pCO2 45.8 mmHg, base excess -10.1 mmol/L). The patient's serum ethanol concentration, obtained at admission, was 43 mg/dL. With supportive care, including IV fluid administration, the patient gradually recovered within 12 hours post-admission. An interview with the parents, 24 hours post-admission revealed, that the infant's formula had been inadvertently mixed with 10 mL of sake (Japanese wine prepared from fermented rice). Follow up of the patient over the next 12 months showed no evidence of psychomotor sequelae (Zaitsu et al, 2013).

a) Ethanol and other alcohols can cause drying and irritation of the skin with repeated or prolonged exposure as a result of skin defatting (Ophaswongse & Maibach, 1994).

a) Allergic contact urticaria has been reported as a result of ethanol exposure. Impurities, decomposition products, or metabolites may be responsible for the sensitization (Ophaswongse & Maibach, 1994).

a) HAND SANITIZERS: In a retrospective review of 647 pediatric (age range, 1 month to 5 years; mean age, 1.89 years) exposures to ethanol-based hand sanitizers (599 ingestions, 105 dermal, 29 ocular, and 2 inhalational), dermal erythema developed in 4 patients (Mrvos & Krenzelok, 2009).

a) Acute and chronic skeletal myopathies have been recorded in ethanol abusers (Estruch et al, 1993; Myerson & Rubin, 1992).
b) Muscle weakness, with or without pain, myoglobinuria, or hypokalemia can occur in chronic alcoholics after large ethanol ingestions (Estruch et al, 1993; Martin et al, 1971).
c) BRACHIAL PLEXOPATHY: Brachial plexopathy, characterized by profound weakness in the affected limbs, was associated with ethanol intoxication in 2 alcoholic patients and was thought to be the result of either stretch or compression of the plexus while intoxicated. The brachial plexopathy was also associated with rhabdomyolysis in one of the patients, due to either direct ethanol myotoxicity or prolonged immobilization on a hard surface, or a combination of both (Silber et al, 1999). Both patients recovered within 4 months after presentation.

a) Low bone density and higher serum calcium levels, suggestive of loss of calcium from bone into the blood, were seen in a group of 26 chronic heavy drinkers in the absence of liver disease (Diez et al, 1994).

a) Rhabdomyolysis developed following acute ethanol use in a person who had a history of frequent alcoholic binges (Pittman & Decker, 1971) and in an abstinent alcoholic who had pneumonia and sepsis (Ifudu & Markel, 1992).

a) Hypoglycemia, which can result in seizures and coma, is a serious complication of acute alcoholic intoxication, especially in children (Hornfeldt, 1992; Selbst et al, 1985; Ricci & Hoffman, 1982; Cummins, 1961). Hypoglycemia has occasionally been reported in alcoholics (Kallas & Sellers, 1975; Field et al, 1963).
b) PEDIATRIC CASE SERIES: In one series of 27 children who had acutely ingested ethanol, 6 (22%) developed a blood sugar less than 40 mg/dL (2.2 mmol/L), and 1 had a seizure (Leung, 1986).
c) PEDIATRIC CASE SERIES: In another series of 109 cases of pediatric mouthwash ingestion, hypoglycemia was documented in 2 of 59, with adequate follow-up (Henretig & Vuignier, 1989).
d) CASE REPORT: Fatality secondary to hypoglycemia was reported in a 4 -year old who ingested an estimated 12 ounces of a mouthwash containing 10% ethanol (Selbst et al, 1985).

a) Hyperglycemia has been reported in a case of ethanol withdrawal (Flannery et al, 1991) and in alcoholics, many of whom were acidotic (Braden et al, 1993; Lieber & DeCarli, 1991; Kallas & Sellers, 1975; Jenkins et al, 1971).
b) CASE REPORT (INFANT): A 9-week-old infant presented to the emergency department acting "strangely" and smelling of alcohol. Examination of the infant revealed decreased mental status and vital signs indicated an increased heart rate (160 beats/minute) and respirations (22 breaths/minute). Interview of the family revealed that the grandmother had inadvertently prepared the child's formula with 90 mL of vodka instead of water. The patient's blood glucose concentration, obtained by fingerstick at admission and at 1 hour and 3 hours postadmission, was 167 mg/dL, 160 mg/dL, and 98 mg/dL, respectively. His serum blood alcohol level, obtained at presentation, was 330 mg/dL. Three hours and 24 hours later, the blood alcohol level decreased to 0.27 mg/dL and less than 0.01 mg/dL, respectively. Following IV administration of 5% dextrose with normal saline (D5NS), the patient recovered and was discharged to home approximately 24 hours postadmission (Minera & Robinson, 2014).

a) PSEUDO-CUSHING SYNDROME: Four cases of alcoholics who presented with clinical and biochemical characteristics that suggested Cushing syndrome have been reported. Discontinuation of ethanol resulted in disappearance of the cushingoid manifestations (Rees et al, 1977).

a) HYPOTHALAMIC-PITUITARY-GONADAL HORMONES: Acute ethanol ingestion (1.3 g/kg) in 7 healthy, nonalcoholic men resulted in transiently increased plasma prolactin and decreased plasma testosterone, cortisol, and adrenocorticotropic hormone levels, with no significant effects on luteinizing hormone during the 180-minute postingestion monitoring period. Similar effects on prolactin and testosterone occurred with daily ethanol for 7 days; plasma measurements were only made for 60 minutes postingestion (Ida et al, 1992).
b) Significant elevations of plasma cortisol have occurred in men during ethanol withdrawal (Adinoff et al, 1991).

a) An anaphylactic reaction due to an immediate-type allergy to acetic acid, the main metabolite of ethanol, has been reported in a 22-year-old woman following the ingestion of as little as 1 mL of ethanol (Przybilla & Ring, 1983). Wine, but not other ethanol-containing beverages, resulted in anaphylaxis in another case, indicating that something in wine other than ethanol was the likely causative agent (Clayton & Busse, 1980).

a) A late-phase allergic reaction (IgE-mediated), characterized by pruritic erythema and edema, was reported in a woman after ingesting ethanol or using dermal preparations containing ethanol (Kanzaki & Hori, 1991).
b) Allergic contact urticaria has been reported as a result of ethanol exposure. Impurities, decomposition products, or metabolites may be responsible for the sensitization (Ophaswongse & Maibach, 1994a). Urticaria associated with ethanol use, but possibly due to trace quinine, has also been reported (Ting, 1992).

a) IMMUNOSUPPRESSION/IMMUNOSTIMULATION: Variable results concerning ethanol-associated immunologic effects have been reported in humans and animals. Genetic predisposition may contribute to individual susceptibility or resistance to the effects of ethanol, based on animal studies that demonstrated strain-related differences in ethanol-associated immunologic effects (Razani-Boroujerdi et al, 1994).
b) Acute versus chronic administration of ethanol also produces different immunologic responses in animals. Decreased circulating cytokines have resulted from acute ethanol, but increased or unaltered cytokine levels were associated with chronic ethanol administration (Marway et al, 1994).
c) Increased susceptibility to Listeria monocytogenes and decreased splenic expression of cytokine (IL-2) genes have been reported in rats fed ethanol for 7 days. Ethanol treatment did not significantly affect clearance of L monocytogenes and did not alter inflammatory cell recruitment to the site of infection (Jerrells et al, 1992).

a) DOSE: It is unclear what dose of ethanol is necessary to cause adverse effects in an individual; however, FAS has been documented in infants of mothers who consume large amounts of alcohol throughout their pregnancy (80 mL daily).
b) INCIDENCE: FAS has been reported to occur at a frequency of 4 to 7 per 1000 live births, or, more conservatively, at 0.33 per 1000 live births in the Western world. According to another estimate, approximately 1 of 3 children of alcoholic mothers will have FAS.
c) It is unlikely that a single acute overdose would be responsible for these effects, but "binge" drinking early in pregnancy and chronic heavy abuse throughout pregnancy have been associated with the syndrome.
d) The question of whether "social drinking" causes FAS is unanswered at this time; hence, a safe level of exposure cannot be determined. The actual mechanism(s) of FAS is not well understood, with the offspring of only a small percentage of alcoholic women being affected. However, the association with ethanol is clear.
e) (Streissguth et al, 1994a; Filley & Kelly, 1993; Abel & Sokol, 1991; Boyd et al, 1991; Coles et al, 1991; Eliason & Williams, 1990; Galea & Goel, 1989; Hill et al, 1989; Abel, 1984; Rosett, 1983; Little & Streissguth, 1981; Jones & Smith, 1973).
f) Black inner-city children had deficits in Bayley Scale performance, regardless of the trimester in which the mother drank ethanol. Incidence of very poor performance was twice as high in the group whose mothers drank at least 0.5 ounces (oz) of ethanol per day. These developmental defects were seen with maternal alcohol ingestions LESS THAN THOSE ASSOCIATED WITH FETAL ALCOHOL SYNDROME (Jacobson et al, 1993).
g) Decreased psychomotor development at age 4.5 years, measured as a decrease of 7 points on the general cognitive index of the McCarthy Scales, was associated with maternal consumption of 1.5 oz or more (approximately 3 drinks per day) during pregnancy, in a group of 155 French children. This level of consumption is well below that required for development of fetal alcohol syndrome (Larroque et al, 1995).
h) Fetal alcohol syndrome is not confined to infancy and childhood. Although the abnormal physical appearance seems to lessen with age, neurodevelopmental deficits continue well into adolescence and adulthood. In one study, the average IQ of adolescents and adults born with fetal alcohol syndrome was considerably lower than average, and maladaptive behaviors were common (Streissguth et al, 1991).
i) The dose-response relationships between maternal alcohol consumption and risks for various fetal effects are not well defined. Although heavy ethanol drinking is clearly a risk factor (Ouellette et al, 1977), even moderate drinking (approximately 1 oz per day) has also been associated with fetal alcohol syndrome (Ernhart, 1985; Hanson, 1978) .
j) Low birth weight has been linked in a dose-related manner with maternal alcohol consumption in the National Natality Survey, even with moderate alcohol ingestion (1 to 13 drinks per week) (Virji, 1991).

a) Ethanol has produced apoptotic neurodegeneration in the developing rat forebrain, which may explain the reduced brain mass associated with human fetal alcohol syndrome (Ikonomidou et al, 2000). Exposure to ethanol at a concentration of 280 to 300 mg/dL leads to increased production of chorionic gonadotrophic hormone in human placental trophoblasts in culture (Fisher, 1993).

a) Ethanol given at levels up to 6.4% of the diet by volume potentiated the activity of 80,000 International Units of vitamin A in reducing fetal size and inducing cleft palate, supernumerary ribs, and misshapen zygomatic arch in fetal rats (Whitby et al, 1994).
b) Aspirin decreased the birth defects in rats caused by ethanol, without significantly altering the mothers' blood alcohol levels (Randall et al, 1991). Exposure to 500 mg% ethanol in mouse whole embryo culture produced superoxide anions, increased levels of lipid peroxidation and cell death, and a 63% incidence of failure to close the anterior neural tube. Diminishment of these effects by superoxide dismutase indicates a free-radical mechanism for ethanol's effects (Kotch et al, 1995).

a) Significantly decreased cranial dimensions, decreased mandibular growth, and decreased birth weight were produced in rats exposed in utero (gestational day 6 to 20) to ethanol. Maternal weight gain was significantly depressed by ethanol consumption (Edwards & Dow-Edwards, 1991).
b) There is extensive literature on the reproductive effects of ethanol in laboratory animals. Typically, lower birth weights, retarded development, and structural malformations have been produced in many species when ethanol is given to the pregnant female. The spectrum of effects in the offspring is generally similar to that reported in humans (Heminki & Vineis, 1985). Ethanol is equally fetotoxic in experimental animals through inhalation or oral exposure (Shoemaker, 1981).
c) In rats, reduction of birth weight is a sensitive indicator of ethanol exposure during gestation, even after adjustment for differences in caloric intake (Hannigan et al, 1993). Prenatal exposure to ethanol produced smaller numbers of neurons in the principal sensory nucleus of the trigeminal nerve in rats; early postnatal exposure produced less of a reduction (Miller, 1995).
d) In rats, prenatal exposure to ethanol depressed the postnatal surge of testosterone, which is required for normal sexual development in males (McGivern et al, 1993).

a) A significantly increased incidence of hydronephrosis and hydroureter was reported in mouse fetuses born to dams exposed to ethanol once on gestational day 10 (Boggan et al, 1989).

a) Performance deficits were suggested to begin with the calculated ethanol dose of 1 ounce/day (2 drinks); the typical pattern of drinking was 4 to 5 drinks per day on a less than daily basis. Infrequent binge drinking (eg, 1 or 2 episodes) or current ethanol use by the caregiver did not appear to correlate positively with the information processing/play behavior effects (Jacobson et al, 1993).

a) Dose-related hyperactivity was seen in guinea pigs exposed prenatally to 3 to 5 g/kg/day ethanol, which persisted into adulthood (Catlin et al, 1993).
b) Sexual orientation was altered in the male offspring of pregnant mice given oral doses of 2 or 4 g/kg ethanol twice per day during the final third of gestation: The males showed an increased preference for sexual partners of the same sex (Watabe & Endo, 1994). Whether this unusual finding has any relevance to human reproduction is unknown.

a) Constriction of the ductus arteriosus was seen in fetal rats within 30 minutes of exposure of the dams to 20 mg/kg of ethanol on day 20 of gestation (Arishima et al, 1993).

a) T-cell function in the offspring of Macaca nemestrina monkeys was depressed when the mothers received weekly oral doses of 1.8 g/kg ethanol during gestation, as measured by lower titers to tetanus toxoid after vaccination (Grossmann et al, 1993).

a) Ethanol produced nerve damage in dog pups when given orally to the pregnant females at the high dose of 500 mL per day throughout the pregnancy (HSDB , 2000). It also affected myelinization of the nerves in rats when present at 6.6% in the diet (Clayton & Clayton, 1982).

a) The mother had been prescribed vodka 30 mL orally 3 times/day for 2 days, and then 30 mL vodka orally per hour for 12 hours until the woman was hospitalized. During hospitalization, 10 mg morphine and 160 g ethanol were infused IV until the mother became unresponsive and unconscious.
b) Blood ethanol levels postdelivery were as high as 715 mg/dL in the infant and 473 mg/dL in the mother; the therapeutic ethanol blood levels for prevention of premature delivery were reported as 90 to 160 mg/dL.

a) Ethanol may have subtle reproductive effects in experimental animals at low doses. Fetuses from pregnant mice maintained at a blood ethanol concentration of 0.03 mg/mL had increased prenatal mortality but no overt malformations (Ukita et al, 1993).

a) In rats, prenatal exposure to ethanol depressed the postnatal surge of testosterone, which is required for normal sexual development in males (McGivern et al, 1993).

a) Ethanol has also been reported to interact with other chemicals to affect reproduction in experimental animals. It was synergistic with marijuana in producing fetotoxicity in mice and rats (Abel, 1985). Ethanol interacted with ethoxyethanol, a common industrial solvent, to produce behavioral and neurochemical effects in the offspring of rats (Nelson, 1984). It interacted with xylene in producing embryotoxicity in rats but was not teratogenic (Ungvary, 1985).

a) MOTOR DEVELOPMENT: One study found a significant, dose-related relationship between ethanol use by breastfeeding mothers and impaired motor development in the nursing infants, after controlling for more than 100 confounding variables. Breast milk ethanol concentrations were estimated and not directly measured(Little et al, 1989).

a) Delayed eye opening, decreased activity, ataxia, tremors, and slowness were reported in rat pups who nursed ethanol-fed dams. Ethanol was present in the blood of the rat pups (Hekmatpanah et al, 1994).

a) HISTOPATHOLOGY: Rat pups of dams fed ethanol had decreased brain weights at 15 days of age (but not at 30 or 60 days), reduced brain myelin formation, and degenerative changes in and delayed maturation of the Purkinje cells, as compared with controls (Hekmatpanah et al, 1994).

a) Ethanol can be passed into the breast milk of nursing mothers (AMA, 1985). The amount of alcohol ingested by nursing infants was estimated to be only 0.5% to 3.3% of the maternal dose on a weight basis (1.6 to 9.9 mg/kg). Alcohol inhibits the breast milk letdown reflex mediated by oxytocin (Mennella & Beauchamp, 1992).

a) There were several limitations of the analysis. Only 1 measure of alcohol consumption at baseline was taken, and the history of lifetime alcohol consumption was not documented; drinking patterns and duration of alcohol use were not examined, and there was no information on screening for colorectal cancer (Cho et al, 2004).

a) The lethal dose is variable, depending in part on chronic versus infrequent ethanol use (Haddad et al, 1998). Coingestion of sedative hypnotics, tranquilizers, anticonvulsants, antidepressants, opioids, or related drugs can compound the adverse effects of ethanol (Rall, 1990).
b) Interpretation of postmortem blood alcohol concentration (BAC) may be dependent upon several factors. During putrefaction, alcohol may be lost due to evaporation or may be produced by microbial activity, or postmortem alcohol diffusion from the stomach contents may occur if the stomach alcohol concentration (SAC) is greater than the BAC. For correct interpretation of BAC and SAC, especially if putrefaction is present, several specimens should be collected for analysis of alcohol concentration, including the vitreous humor, bile, synovial fluid, cerebrospinal, chest, or intra-abdominal fluid, inner ear fluid, and/or urine. These body fluids are isolated and protected within various body cavities and are less likely to be subjected to alcohol diffusion or production via microbial activity (Athanaselis et al, 2005).

a) A blood ethanol concentration of 150 mg% (32.5 mmol/L) increases osmolality by 21.6 milliosmoles/kg water.
b) The following equation correlates well with BAC (Weiss & Thurnheer, 1988): BAL (g/L) = osmolal gap/27

a) CAPNOGRAPHY is a noninvasive method used to determine respiratory depression in adolescents with acute alcohol intoxication via monitoring of decreasing tidal volumes, as measured by end-tidal carbon dioxide (ETCO2) of less than 30 mmHg, and decreasing respiratory rates, as measured by ETCO2 greater than 50 mmHg (Langhan, 2013).

1) Another study disagrees with the above conclusions and asserts that ingestion of ethanol-containing products by small children must be evaluated according to a calculation of maximum possible ingested dose per kg body weight. For example, a lethal dose of a perfume containing 90% ethanol by a 10 kg, 12-month-old child could be as little as 42.2 mL (Silverman, 1990).

a) In several crossover human studies, administration of from 20 g of activated charcoal to 60 g of superactivated charcoal, given 5 to 30 minutes before or after an ethanol load (resulting in blood ethanol levels of 100 to 130 mg%) had no effect on ethanol absorption (Minocha et al, 1986; Hulten et al, 1985; Olkkola, 1985; Neuvonen et al, 1984).
b) Two human studies indicate that ethanol only slightly decreases the effectiveness of activated charcoal in preventing aspirin or quinidine sulfate absorption (Cooney, 1995). Results of a study conducted in mice indicated that ethanol may decrease the adsorptive capacity of charcoal for strychnine (Olkkola, 1985).

a) Naloxone may antagonize the depressant effect following acute ethanol overdose (Rae, 1986; Lyon & Antony, 1982; Sorensen & Mattisson, 1978), but this effect does not appear to be predictable or consistent in humans (Mattila et al, 1981; Jeffreys et al, 1980) or animals (Lignian et al, 1982).

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) A prospective, randomized, placebo-controlled, double-blind study of 55 patients who had seized from alcohol withdrawal tested the efficacy of phenytoin in preventing further withdrawal seizures (Chance, 1991). In this study, phenytoin did not prevent further withdrawal seizures any more than did placebo.
b) Another study involving 100 adults reported that there was no significant difference in seizure activity during ethanol withdrawal among phenytoin-treated (15 mg/kg; mean phenytoin blood level of 16 mcg/mL) and placebo-treated patients (Rathlev et al, 1994). The period of observation posttreatment was 6 hours.

a) Eighteen ethanol-overdose patients were dosed in a double-blind fashion with either placebo or 1 mg flumazenil. Improvement in conscious state, as measured by Glasgow Coma Scale, was no greater for flumazenil-dosed patients than for those who got placebo (Lheureux & Askenasi, 1991).
b) Eight adult male volunteers with a mean blood ethanol level of 1.6 g/L received either placebo or flumazenil 5 mg and were evaluated with psychomotor and cognitive function tests at 15 and 75 minutes post-dosing (Clausen et al, 1990).
c) ANIMALS: Mice were habituated to oral ethanol for 10 days and then were given a single injection of flumazenil (10 mg/kg) 14 hours prior to ethanol withdrawal.

a) Flumazenil should not be used in patients with serious cyclic antidepressant poisoning, as manifested by motor abnormalities (twitching, rigidity, seizure), dysrhythmias (wide QRS, ventricular dysrhythmia, heart block), anticholinergic signs (mydriasis, dry mucosa, hypoperistalsis), or cardiovascular collapse at presentation (Prod Info ROMAZICON(R) IV injection, 2004).
b) Flumazenil should not be used in patients who are benzodiazepine-dependent or who have been given benzodiazepines for control of a life-threatening condition (Thomson et al, 2006; Prod Info ROMAZICON(R) IV injection, 2004).
c) There is no known benefit of treatment with flumazenil in a mixed-drug overdose patient who is in critical condition. Flumazenil should NOT be used in cases where seizures are likely, from any cause (Thomson et al, 2006; Prod Info ROMAZICON(R) IV injection, 2004) .

a) Fructose can cause nausea and vomiting, intensify lactic acidosis, and reduce blood volume through osmotic diuresis.
b) It is contraindicated in patients with advanced liver disease, uncontrolled diabetes mellitus, and hyperuricemic states.

a) Picamilon-treated cases required lower benzodiazepine doses, had improved trembling test scores, no apparent complications, mild sedation, and significantly reduced systolic blood pressure and systemic vascular resistance, as compared with controls (Afanasiev et al, 1995).

a) SUMMARY
b) ADULT
c) MAXIMUM SURVIVED BLOOD ETHANOL LEVELS (ADULTS)
d) MAXIMUM SURVIVED BLOOD ETHANOL LEVELS (PEDIATRIC)
e) PERCUTANEOUS EXPOSURE
f) ACUTE INTOXICATION
g) ASYMPTOMATIC PATIENTS

1) Ethanol

a) TWA: 1000 ppm (1900 mg/m(3))
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s):

a) IDLH: 3300 ppm
b) Note(s): [10%LEL]

a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.

a) Category 5 : Substances with carcinogenic and genotoxic effects, the potency of which is considered to be so low that, provided the MAK and BAT values are observed, no significant contribution to human cancer risk is to be expected. The classification is supported by information on the mode of action, dose dependence and toxicokinetic data pertinent to species comparison.

a) 8-hour TWA:

a) 528 mg/kg

a) 220 mg/kg (OHM/TADS , 2002a)
b) 3450 mg/kg

a) 8285 mg/kg

a) 11 mg/kg -- chronic pulmonary edema; dyspnea

a) 1225 mg/kg (OHM/TADS , 2002a)
b) 3600 mcg/kg
c) 5000 mg/kg (OHM/TADS , 2002a)

a) 7060 mg/kg -- respiratory changes
b) 7800 mg/kg (OHM/TADS , 2002a)
c) 13,700 mg/kg (OHM/TADS , 2002a)

a) female, 20,000 ppm for 7H at 1 to 22D of pregnancy -- developmental abnormalities

1) Four individuals with histories of ethanol-induced variant angina and significant coronary artery stenosis developed coronary spasm after alcohol challenge. These cases had statistically significant increased thromboxane, decreased 6-ketoprostaglandin F1-alpha, and decreased cyclic guanosine monophosphate, as compared with controls (Oda et al, 1994).
2) Study results suggest that ethanol-induced magnesium deficiency may predispose some individuals to ethanol-induced angina (Miwa et al, 1994).

1) Decreased lipid oxidation by the liver
2) Decreased hepatic clearance of lipoprotein
3) Enhanced hepatic lipogenesis
4) Enhanced uptake of circulating lipids
5) Increased mobilization of peripheral fat