Ferrous nitrilotriacetate

/ALTERNATIVE IN VITRO TESTS/ ...Localization of 59Fe-labeled NTA radioactivity in mouse liver and accumulation of thiobarbituric acid (TBA)-reacting material in liver after ip injection suggested that the effect of ip iron-NTA could be primarily hepatic. It was found that 100 uM iron-NTA added to a hepatocyte suspension gassed with air stimulated ethane production (3 +/- 1 pmoles/10+6 cells/min) versus an undetectable control, and at a sensitivity of 0.083 pmole/10+6 cells/min. Under similar conditions, hepatocytes stimulated by iron-NTA generated low level chemiluminescence (Cl) in parallel with formation of TBA-reactants; the generation of Cl was concentration related. Liver was homogenized and fractionated by ultracentrifugation: iron-NTA stimulated Cl in whole liver homogenate as in intact cells. The greater part of this activity localized to the microsomal and mitochondrial fractions where NADH or NADPH was required. Using rat liver microsomes, it was shown that iron-NTA in the presence of NADPH stimulated two phases of Cl with an initial phase maximum in 1-2 min (phase 1) which decreased abruptly to be followed by a prolonged rise (phase 2); NADH could replace NADPH. Ferrous iron (as chloride) caused a burst of Cl, whereas ferric iron was inactive. However, complex differences exist between Cl stimulated by Fe(II) and by iron-NTA in the presence of reducing equivalents. Under conditions resulting in the production of Cl, a microsomal system with iron-NTA and reducing equivalent accumulated TBA-reactants in parallel with the stimulated Cl and rapid increase in oxygen consumption. Both desferrioxamine and butylated hydroxyanisole were able to strongly inhibit the Cl stimulated by iron-NTA. When iron-NTA and iron-ADP were compared in the microsomal system, similar responses were obtained but major differences characterized the effects of these iron chelates on whole cells with the ADP complex being relatively inactive.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. /Iron and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with lactated Ringer's /SRP: "To keep open", minimal flow rate/. Watch for signs of fluid overload. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Iron and related compounds/

Maintain an open airway and assist ventilation if necessary. Treat shock caused by hemorrhagic gastrointestinitis aggressively with intravenous crystalloid fluids, and replace blood if needed. Patients are often markedly hypovolemic owing to gastrointestinal losses and third spacing of fluids into the intestinal wall and interstitial space. Treat coma, seizures, and metabolic acidosis if they occur. For seriously intoxicated victims (eg, shock, severe acidosis, and/or serum iron > 500-600 mcg/dL) administer deferoxamine. Monitor the urine for the urine for the characteristic orange or pink deferoxamine-iron complex. Therapy may be stopped when the urine returns to normal or when the serum iron level decreases to the normal range. Prolonged deferoxamine has been associated with adult respiratory distress syndrome and Yersinia sepsis.

Activated charcoal is not effective. Ipecac is not recommended, because it can aggravate iron-induced gastrointestinal irritation and interfere with whole bowel irrigation. Consider gastric lavage if product was a liquid formulation or tablets were chewed. Do-not use phosphate-containing solutions for lavage; these may result in life-threatening hypernatremia, hyperphosphatemia, and hypocalcemia. Bicarbonate and deferoxamine lavage are of doubtful efficacy. Deferoxamine lavage is not effective and may enhance iron absorption. Whole-bowel irrigation is very effective for ingested tablets and may be considered first-line treatment, especially if large numbers of tablets are visible on plain abdominal x-ray. Massive ingestions may lead to concretions or bezoars. Repeated or prolonged whole-bowel irrigation may remove tablets. Endoscopy or surgical gastrotomy is rarely required.

Hemodialysis and hemoperfusion are not effective for removing iron but may be necessary to remove iron-deferoxamine complex in patients with renal failure. Exchange transfusion is occasionally used for massive pediatric ingestions but is of questionable efficacy.