a) Vasodilatation may occur, leading to hypotension, syncope, and tachycardia (Prod Info sodium nitrite intravenous injection, 2010).

a) Tachycardia has been frequently reported with sodium nitrite poisoning (Tung et al, 2006; Gowans, 1990a; Kaplan et al, 1990; Aquanno et al, 1981; Sevier & Berbatis, 1976a).
b) CASE REPORT: Following ingestion of approximately 0.7 g sodium nitrite in contaminated drinking water, a 34-year-old woman developed cyanosis and sinus tachycardia (108 beats/min) associated with a methemoglobin level of 49% (Bradberry et al, 1994).

a) Hypotension may occur with sodium nitrite poisoning (Bradberry et al, 1994; Gowans, 1990; Kaplan et al, 1990; Ten Brink et al, 1982).

a) CASE SERIES: Twenty-two people experienced dyspnea and vomiting approximately 10 minutes after consuming a meal, later identified as contaminated with a substance containing sodium nitrite and potassium arsenate. The substance was added to the meal, mistakenly believed to be table salt. Fourteen of the 22 patients died within 2 to 3 hours postingestion, after developing peripheral cyanosis and circulatory failure. Postmortem analysis revealed elevated nitrite concentrations in the gastric contents (54.9 +/-17.9 mcg/mL) (Gautami et al, 1995).

a) Cyanosis that does not respond to oxygen administration is a hallmark of significant methemoglobinemia.
b) Peripheral and generalized cyanosis is a frequent occurrence with sodium nitrite poisoning (Tung et al, 2006; Finan et al, 1998; Saito et al, 1996a; Ellis et al, 1992a; Gowans, 1990a; Kaplan et al, 1990; Aquanno et al, 1981; Sevier & Berbatis, 1976a).
c) CASE SERIES: Twenty-two people experienced dyspnea and vomiting approximately 10 minutes after consuming a meal, later identified as contaminated with a substance containing sodium nitrite and potassium arsenate. The substance was added to the meal, mistakenly believed to be table salt. Fourteen of the 22 patients died within 2 to 3 hours postingestion, after developing peripheral cyanosis and circulatory failure. Postmortem analysis revealed elevated nitrite concentrations in the gastric contents (54.9 +/-17.9 mcg/mL) (Gautami et al, 1995),
d) CASE REPORT: Following ingestion of approximately 0.7 g sodium nitrite in contaminated drinking water, a 34-year-old woman developed cyanosis and sinus tachycardia (108 beats/minute) associated with a methemoglobin level of 49% (Bradberry et al, 1994).

a) Tachypnea has been frequently reported with sodium nitrite poisoning (Gowans, 1990a; Kaplan et al, 1990; Sevier & Berbatis, 1976a).

a) Headaches and dizziness may occur as a result of sodium nitrite-induced vasodilatation following therapeutic administration (Prod Info sodium nitrite intravenous injection, 2010).
b) During an open three-way crossover study, involving 9 volunteers, mild headaches were reported in 5 people following intravenous administration of 0.12 mmol sodium nitrate/mmol hemoglobin, with onset occurring between 30 minutes and 6 hours after administration. Headaches were also reported in 4 people following oral administration of 0.12 and 0.06 mmol sodium nitrite/mmol hemoglobin (onset was between 25 minutes and 3.8 hours and between 15 minutes and 5.5 hours postingestion, respectively). In all patients, the headaches persisted between 0.5 hours and 23 hours after onset (Hunault et al, 2009).

a) Numbness and tingling of the extremities were reported in 2 patients who inadvertently ingested sodium nitrite, mistakenly believed to be table salt. Both patients also developed tachycardia, peripheral cyanosis, and methemoglobinemia, but recovered following treatment with methylene blue (Aquanno et al, 1981).

a) Decreased levels of consciousness, including coma, have been reported with sodium nitrite poisoning (Gautami et al, 1995a; Ellis et al, 1992a; Kaplan et al, 1990; Ten Brink et al, 1982).
b) CASE SERIES (CHILDREN): Three children (4-year-old twin boys and their 2-year-old sister) presented to the emergency department with one of the twins severely cyanotic and the other 2 children developing cyanosis approximately 10 minutes after presentation. All 3 children demonstrated decreased levels of consciousness, necessitating mechanical ventilation of 2 of the children. Methemoglobin concentrations of the 4-year-old twins were 38% and 77%. Following administration of intravenous methylene blue, all 3 children recovered without neurologic sequelae. Further investigation revealed that the children had ingested bottles of milky tea, thought to be sweetened with sugar, but were instead contaminated with sodium nitrite. Analysis of the 3 bottles of tea revealed nitrite concentrations ranging from 4940 mg/L to 5100 mg/L (Finan et al, 1998).

a) Seizures may occur following sodium nitrite poisoning (Prod Info sodium nitrite intravenous injection, 2010; Ten Brink et al, 1982).

a) Nausea and vomiting may occur with sodium nitrite therapy (Prod Info sodium nitrite intravenous injection, 2010).
b) During an open three-way crossover study, nausea was reported in 1 subject (n=9) following intravenous administration of 0.12 mmol sodium nitrite/mmol hemoglobin. Following oral administration of 0.12 mmol sodium nitrite/mmol hemoglobin, nausea was reported in 2 patients within 30 minutes postingestion. The nausea resolved, in all cases, within 30 minutes of onset (Hunault et al, 2009).

a) Nausea and vomiting are common with sodium nitrite poisoning (Gautami et al, 1995; Bradberry et al, 1994; Sevier & Berbatis, 1976a).

a) Abdominal pain has been reported with therapeutic administration of sodium nitrite (Prod Info sodium nitrite intravenous injection, 2010).

a) Severe abdominal spasms have been prominent in fatal cases presenting with gastrointestinal inflammation at autopsy (McQuiston, 1936; Barton, 1954).

a) CASE REPORT (CHILD): A 4-year-old child was lethargic and experienced one episode of vomiting following application, over his entire body, of a liniment solution that contained 30 g/L of sodium nitrite. Following application of another liniment solution, containing 140 g/L of sodium nitrite, over his entire body, he immediately developed severe cyanosis and metabolic acidosis. Despite intensive supportive therapy, the patient died 2 hours after admission. Postmortem analysis of his blood revealed the blood to be a chocolate-brown color with a methemoglobin concentration of 76% (Saito et al, 1996).

a) Methemoglobinemia commonly occurs with sodium nitrite toxicity. Although symptoms of methemoglobinemia can occur at blood methemoglobin concentrations of 15%, typically symptoms may not appear until methemoglobin concentrations are 30% or greater (Prod Info sodium nitrite intravenous injection, 2010). Patients with anemia, or chronic cardiac or pulmonary conditions are usually symptomatic at lower methemoglobin concentrations.
b) CASE REPORT: A 17-year-old woman presented with cyanosis, tachycardia, and tachypnea after ingestion of a single 1-g sodium nitrite tablet. Approximately 15 minutes after hospital admission, the patient was mechanically ventilated after vomiting, aspiration, and subsequent respiratory arrest. Despite the cyanosis, the patient's arterial blood gases were normal (calculated saturation), however a venous blood sample was chocolate brown, suggesting methemoglobinemia. Although methylene blue was administered 30 minutes later, the patient developed severe hypotension and cardiac dysrhythmias, refractory to placement of a temporary pacing wire and resuscitative efforts, and she died 2 hours after admission. Postmortem analysis revealed a methemoglobin concentration of 35% and a serum nitrite ion concentration of 13 mg/L (Gowans, 1990a).
c) CASE REPORTS: Methemoglobinemia, with fatalities in some instances, were reported in several patients who inadvertently ingested sodium nitrite believed to be table salt or sodium chloride tablets. The patients also experienced tachycardia, nausea and vomiting, tachypnea, dyspnea, and cyanosis. The methemoglobin concentrations ranged from 17% to 87% (Tung et al, 2006; Centers for Disease Control and Prevention, 2002; Gautami et al, 1995; Kaplan et al, 1990; Aquanno et al, 1981; Wilson, 1976; Sevier & Berbatis, 1976a). Other cases of methemoglobinemia have occurred following ingestion of a laxative solution contaminated with sodium nitrite (15 g/L) (Ellis et al, 1992), ingestion of drinking water contaminated with an anticorrosive agent containing 30% sodium nitrite (Bradberry et al, 1994), and ingestion of food items contaminated with sodium nitrite that occurred from a leaking cooling system during transportation of the items to the supermarket. Analysis of unopened food packages where the patients had shopped revealed sodium nitrite in concentrations up to 5% (Ten Brink et al, 1982a). It has also happened following intentional ingestion of a synthetic dye containing sodium nitrite (Saigal et al, 2014).
d) CASE REPORT (CHILD) DERMAL ABSORPTION: A 4-year-old child was lethargic and experienced one episode of vomiting following application, over his entire body, of a liniment solution that contained 30 g/L of sodium nitrite. Following application of another liniment solution, containing 140 g/L of sodium nitrite, over his entire body, he immediately developed severe cyanosis and metabolic acidosis. Despite intensive supportive therapy, the patient died 2 hours after admission. Postmortem analysis of his blood revealed the blood to be a chocolate-brown color with a methemoglobin concentration of 76% (Saito et al, 1996).
e) CASE REPORT (CHILD): A 16-month-old child presented to the emergency department with alternating periods of agitation and lethargy after ingesting an industrial cleaning solution containing 50% cationic detergents, 20% isopropyl alcohol, and 1% sodium nitrite. Physical examination revealed perioral cyanosis, mild respiratory distress, and tachycardia. Pulse oximetry indicated an oxygen saturation of 72% and co-oximetry demonstrated a methemoglobin concentration of 63%. With intravenous administration of methylene blue, the patient completely recovered with a repeat methemoglobin concentration of 2% (Freeman & Wolford, 1996a).
f) CASE SERIES (CHILDREN): Three children (4-year-old twin boys and their 2-year-old sister) presented to the emergency department with one of the twins severely cyanotic and the other two children developing cyanosis approximately 10 minutes post-presentation. All 3 children demonstrated decreased levels of consciousness, necessitating mechanical ventilation of 2 of the children. Methemoglobin concentrations of the 4-year-old twins were 38% and 77%. Following administration of intravenous methylene blue, all 3 children recovered without neurologic sequelae. Further investigation revealed that the children had ingested bottles of milky tea, thought to be sweetened with sugar, but were instead contaminated with sodium nitrite. Analysis of the three bottles of tea revealed nitrite concentrations ranging from 4940 mg/L to 5100 mg/L (Finan et al, 1998).
g) CASE SERIES: Five patients developed dyspnea and cyanosis after consuming meals prepared with a food additive. Laboratory analyses revealed methemoglobin concentrations ranging from 21% to 57%. All 5 patients recovered following intravenous administration of methylene blue. Analysis of the food additive packets that were used indicated that one of the packets, labeled as "Goldfish" brand "Nutre Powder", contained 100% sodium nitrite (Maric et al, 2008).
h) CASE SERIES: Twenty-seven construction workers were inadvertently exposed to sodium nitrite (20% to 50% concentration) after ingesting an antifreeze admixture that was mistaken for water. Six workers required hospital admission with 2 patients requiring intubation. Methemoglobin levels ranged from 32.4% to 71.5%. All patients were treated with methylene blue, and recovered uneventfully with no permanent sequelae (Sohn et al, 2014).

a) Yellow-stained skin occurred on the palms of seven workers who were exposed to an etching agent that was dipped in a bath containing less than 1% sodium nitrite (Fregert et al, 1980).

a) Animal data indicate that sodium nitrite crosses the placenta and can induce methemoglobinemia in the fetus (Prod Info NITHIODOTE intravenous injection solution, 2011; Gruener et al, 1973).
b) RATS: In rats, the fetus has a tenfold higher level of methemoglobin reductase than adult rats or human fetuses (Gruener, 1973). However, pregnant rats are more sensitive to sodium nitrite than nonpregnant rats (Tarburton, 1985).

a) RATS: A dose-related increase in postpartum mortality was noted in pregnant rats who received sodium nitrite in drinking water at concentrations of either 2000 or 3000 mg/L. This exposure would result in an approximate dose of 220 and 300 mg/kg/day, which is 43 and 65 times the highest clinical dose of sodium nitrite that would be used for cyanide poisoning based on a body surface area comparison (Prod Info NITHIODOTE intravenous injection solution, 2011).
b) In several experimental animal studies, sodium nitrite did not cause birth defects, but caused fetal death (Druckrey, 1963).
c) GUINEA PIGS: Pregnant guinea pigs who received 60 or 70 mg/kg/day subQ of sodium nitrite aborted their litters within 1 to 4 days of treatment, and all animals treated with 70 mg/kg/day died within 60 minutes of treatment. Measurable blood levels of methemoglobin in the dams and their fetuses were noted with the 60 mg/kg/day dose for up to 6 hours post-treatment, and maternal methemoglobin levels were higher than those for the offspring for all measurements. The 60 mg/kg/day dose that resulted in death was 1.7 times higher than the highest clinical dose of sodium nitrite that would be used for cyanide poisoning based on a body surface area comparison (Prod Info NITHIODOTE intravenous injection solution, 2011; Sinha & Sleight, 1971). A dose of 50 mg/kg/day of sodium nitrite had no apparent effect on the fetus (Sinha & Sleight, 1971).

a) Pulse oximetry overestimates oxygen saturation in patients with significant methemoglobinemia and should not be used to reflect arterial oxygen content or tissue oxygen delivery (Watcha et al, 1989; Bardoczky et al, 1990; Barker et al, 1989; Varon, 1992; Delwood et al, 1991).
b) Treatment of methemoglobinemia should be guided by patient signs and symptoms. Monitor therapy with direct measurements of oxyhemoglobin using a co-oximeter and not on the basis of measurements using pulse oximetry or on estimates of saturations calculated from the PO2 and the oxyhemoglobin dissociation curve (Watcha et al, 1989). Pulse oximetry may actually register a transient decrease following treatment with methylene blue.

a) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.

a) Monitor mental status and perform a neurologic exam in symptomatic patients.

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) Treatment is primarily symptomatic and supportive. Administer 100% humidified supplemental oxygen. Hypotension can be treated with intravenous fluids; vasopressors may be necessary in patients who do not respond to adequate fluid resuscitation.

a) Methemoglobinemia frequently occurs with sodium nitrite poisoning. Methylene blue is the treatment of choice and is indicated in symptomatic patients. Treat seizures with benzodiazepines; add barbiturates if seizures persist.

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, 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. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

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, 2010; 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):