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Kreozan poisoning

4,6-Dinitro-o-cresol (alias of Kreozan) CAS RN:534-52-1 Treatment Overview 0.4.2 ORAL EXPOSURE A) Caution may be indicated in substantial recent ingestions because the patient may rapidly become obtunded, comatose, or convulsing, thereby at risk of aspiration of gastric contents into the lungs. 1) INDUCTION OF EMESIS - with syrup of ipecac is therefore CONTRAINDICATED. B) DILUTION: Immediately dilute with 4 to 8 ounces (120 to 240 mL) of water or milk (not to exceed 4 ounces/120 mL in a child). C) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation. D) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in Trendelenburg and left lateral decubitus position or by endotracheal intubation. Control any seizures first. 1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion. E) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old. F) MONITORING PARAMETERS - Monitor hepatic and renal function tests. 1) Fluid, electrolyte, blood glucose, and acid-base status should be monitored and abnormalities corrected as indicated. G) All intravenous solutions should contain adequate amounts of glucose to supply the requirements of increased metabolism.

H) HYPERTHERMIA 1) Reduction of hyperthermia with tepid water baths is superior to alcohol sponging or ice packs which tend to constrict the peripheral circulation and could result in heat retention. 2) A rectal electrode thermometer, if available, should be used to monitor core temperature. 3) If tepid bathing is not sufficient, a cooling blanket or bath should be considered. 4) Administration of SALICYLATES to reduce hyperpyrexia is probably CONTRAINDICATED. Aspirin is also an oxidative phosphorylation uncoupler and may aggravate the hyperpyrexia. I) SEIZURES: Administer a benzodiazepine IV; DIAZEPAM (ADULT: 5 to 10 mg, repeat every 10 to 15 min as needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05 to 0.1 mg/kg). 1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children > 5 years). 2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, hypoxia. J) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia. K) Administration of oxygen may assist in minimizing tissue hypoxia. L) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia. M) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans. 1) If cyanosis is present, obtain methemoglobin level and monitor if abnormal. 2) SUMMARY a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (dyspnea, headache, fatigue, CNS depression, tachycardia, acidosis, etc.). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin levels above 20 to 30 percent, but may occur at lower methemoglobin levels in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy. 3) METHYLENE BLUE

a) INITIAL DOSE/ADULT OR CHILD: 1 to 2 milligrams/kilogram/dose (0.1 to 0.2 milliliter/kilogram/dose) intravenously over 5 minutes with a 30 mL flush of normal saline as needed every 4 hours. Improvement is noted shortly after administration if diagnosis is correct. Methylene blue may also be given by intraosseous infusion if intravenous access cannot be established (Herman et al, 1999). NEONATES: 0.3 to 1 milligram/kilogram (Hjelt et al, 1995). b) REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). c) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004) d) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. G-6-PD is essential for the formation of NADPH, and thus necessary for the function of methylene blue. 4) TOLUIDINE BLUE (GERMANY) a) DOSE: 2 to 4 milligrams/kilogram intravenously over 5 minutes. Dose may be repeated in 30 minutes. b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose. c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis. N) Hemodialysis and forced diuresis have not been shown to be effective in poisoning with these agents. Hemoperfusion has not been sufficiently tested to state whether or not it could have any beneficial effect. O) NOTE: See treatment of oral exposure in the main body of this document for complete information. 0.4.3 INHALATION EXPOSURE A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis.

Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. B) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests. C) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases. D) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed. E) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents. F) MONITORING PARAMETERS 1) Monitor hepatic and renal function tests. 2) Fluid, electrolyte, blood glucose, and acid-base status should be monitored and abnormalities corrected as indicated. G) All intravenous solutions should contain adequate amounts of glucose to supply the requirements of increased metabolism. H) HYPERTHERMIA 1) Reduction of hyperthermia with tepid water baths is superior to alcohol sponging or ice packs which tend to constrict the peripheral circulation and could result in heat retention. 2) A rectal electrode thermometer, if available, should be used to monitor core temperature. 3) If tepid bathing is not sufficient, a cooling blanket or bath should be considered. 4) Administration of SALICYLATES to reduce hyperpyrexia is probably CONTRAINDICATED. Aspirin is also an oxidative phosphorylation uncoupler and may aggravate the hyperpyrexia. I) SEIZURES: Administer a benzodiazepine IV; DIAZEPAM (ADULT: 5 to 10 mg, repeat every 10 to 15 min as needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05 to 0.1 mg/kg). 1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children > 5 years).

2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, hypoxia. J) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia. K) Administration of oxygen may assist in minimizing tissue hypoxia. L) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia. M) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans. 1) If cyanosis is present, obtain methemoglobin level and monitor if abnormal. 2) SUMMARY a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (dyspnea, headache, fatigue, CNS depression, tachycardia, acidosis, etc.). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin levels above 20 to 30 percent, but may occur at lower methemoglobin levels in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy. 3) METHYLENE BLUE a) INITIAL DOSE/ADULT OR CHILD: 1 to 2 milligrams/kilogram/dose (0.1 to 0.2 milliliter/kilogram/dose) intravenously over 5 minutes with a 30 mL flush of normal saline as needed every 4 hours. Improvement is noted shortly after administration if diagnosis is correct. Methylene blue may also be given by intraosseous infusion if intravenous access cannot be established (Herman et al, 1999). NEONATES: 0.3 to 1 milligram/kilogram (Hjelt et al, 1995). b) REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). c) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004) d) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to

leukomethylene blue. This in turn reduces methemoglobin. G-6-PD is essential for the formation of NADPH, and thus necessary for the function of methylene blue. 4) TOLUIDINE BLUE (GERMANY) a) DOSE: 2 to 4 milligrams/kilogram intravenously over 5 minutes. Dose may be repeated in 30 minutes. b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose. c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis. N) Hemodialysis and forced diuresis have not been shown to be effective in poisoning with these agents. Hemoperfusion has not been sufficiently tested to state whether or not it could have any beneficial effect. O) NOTE: See treatment of inhalation exposure in the main body of this document for complete information. 0.4.4 EYE EXPOSURE A) DECONTAMINATION: Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. B) No cases of systemic toxicity in humans following ocular exposure to this compound have been reported. Should systemic toxicity develop following eye exposure: 1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate. 0.4.5 DERMAL EXPOSURE A) OVERVIEW 1) DECONTAMINATION: Remove contaminated clothing and jewelry. Wash the skin, including hair and nails, vigorously; do repeated soap washings. Discard contaminated clothing. 2) Cutaneous exposure is usually accompanied by a yellowish discoloration which does not have to be removed entirely to prevent absorption. 3) Severe systemic dinitrophenol poisoning can occur from dermal exposure; hence aggressive and immediate skin decontamination must be undertaken and a physician consulted as soon as possible.

4) MONITORING PARAMETERS a) Monitor hepatic and renal function tests. b) Fluid, electrolyte, blood glucose, and acid-base status should be monitored and abnormalities corrected as indicated. 5) All intravenous solutions should contain adequate amounts of glucose to supply the requirements of increased metabolism. 6) HYPERTHERMIA a) Reduction of hyperthermia with tepid water baths is superior to alcohol sponging or ice packs which tend to constrict the peripheral circulation and could result in heat retention. b) A rectal electrode thermometer, if available, should be used to monitor core temperature. c) If tepid bathing is not sufficient, a cooling blanket or bath should be considered. d) Administration of SALICYLATES to reduce hyperpyrexia is probably CONTRAINDICATED. Aspirin is also an oxidative phosphorylation uncoupler and may aggravate the hyperpyrexia. 7) SEIZURES: Administer a benzodiazepine IV; DIAZEPAM (ADULT: 5 to 10 mg, repeat every 10 to 15 min as needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05 to 0.1 mg/kg). a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children > 5 years). b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, hypoxia. 8) Atropine SHOULD NOT BE ADMINISTERED as it could exacerbate hyperthermia. 9) Administration of oxygen may assist in minimizing tissue hypoxia. 1 0) Agitation should be controlled with such agents as diazepam to prevent further metabolic heat generation which could aggravate the hyperpyrexia. 1 1) Methemoglobinemia has followed administration of dinitro-o-cresol compounds in ruminants. This effect has not been reported in exposed humans. a) If cyanosis is present, obtain methemoglobin level and monitor if abnormal. b) SUMMARY

1) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (dyspnea, headache, fatigue, CNS depression, tachycardia, acidosis, etc.). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin levels above 20 to 30 percent, but may occur at lower methemoglobin levels in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy. c) METHYLENE BLUE 1) INITIAL DOSE/ADULT OR CHILD: 1 to 2 milligrams/kilogram/dose (0.1 to 0.2 milliliter/kilogram/dose) intravenously over 5 minutes with a 30 mL flush of normal saline as needed every 4 hours. Improvement is noted shortly after administration if diagnosis is correct. Methylene blue may also be given by intraosseous infusion if intravenous access cannot be established (Herman et al, 1999). NEONATES: 0.3 to 1 milligram/kilogram (Hjelt et al, 1995). 2) REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). 3) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004) 4) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. G-6-PD is essential for the formation of NADPH, and thus necessary for the function of methylene blue. d) TOLUIDINE BLUE (GERMANY) 1) DOSE: 2 to 4 milligrams/kilogram intravenously over 5 minutes. Dose may be repeated in 30 minutes. 2) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose. 3) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis. 1

2) Hemodialysis and forced diuresis have not been shown to be effective in poisoning with these agents. Hemoperfusion has not been sufficiently tested to state whether or not it could have any beneficial effect. 1 3) NOTE: See treatment of dermal exposure in the main body of this document for complete information.