Ferrous sulfate poisoning

Ferrous sulfate poisoning

218 T h e Journal of P E D I A T R I C S Ferrous sulfate poisoning A r e v i e w , case s u m m a r i e s , and therapeutic regimen The incidence...

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T h e Journal of P E D I A T R I C S

Ferrous sulfate poisoning A r e v i e w , case s u m m a r i e s ,

and therapeutic


The incidence, pathology, and symptoms of acute severe iron poisoning are reviewed. Four cases are presented: the first terminated in death by acute hepatic failure; the second ease with severe first and second phase symptoms was treated successfully with peritoneal dialysis and calcium disodium EDTA; and in the third and fourth cases recovery occurred after treatment by chelation and supportive means. The clinical phases of acute iron poisoning are reviewed, and a logical plan for management is formulated.

Thomas J. Covey, M.D.* V A L P A R A I S O~ I N D .

F ~ R R o u s sulfate poisoning was first reported in American medical literature in t850.1 One half of the 42 recorded poisonings in children occurring in the period from 1947 to 1956 were fatal. T h e smallest dose of ferrous sulfate resulting in death in this series was 3 Gin. while as much as 15 Gin. were ingested with recovery. I n animals the fataI dose is calculated to be 150 to 200 rag. per kilogram. 2 I t is probably safe to assume that as little as 1 Gin. can be fatal to a child? Iron is an important cause of accidental poisoning in children in England with the frequency being comparable to aspirin poisoning in the United States. 4 From 1930 to 1953, fifty-three deaths were recorded in Great Britain. The span from 1950 to 1953 accounted for thirty-two of these fatalities. From the Department of Pediatrics and the Hektoen Institute for Medical Research of the Cook County Hospital, Chicago, Ill. *Address, I She~eld Drive, Valparaiso, Ind.

In addition to establishing the minimal probable fatal dose of ferrous sulfate in children, the Nineteenth Ross Pediatric Research Conference further correlated symptoms and sites of pathology and suggested a specific treatment not previously used? Three critical phases of severe iron poisoning were described. The early acute phase with signs of vomiting of fresh or altered blood, diarrhea and melena accompanied by shock, coma and acidosis occurs within onehalf to one hour of ingestion. Recurrent shock constitutes the second phase and occurs 20 to 48 hours after ingestion. Aldri oh5 classified these phases as initial cardiovascu" lar collapse with death in 6 hours or less if the patient cannot be supported, a period of deceptive improvement for 10 to 14 hours, and a recurrent phase of severe usually irreversible shock within 20 hours of ingestion. Edathamil calcium disodium EDTA was recommended as a possible chelating agent?

Volume 64 Number 2

A late phase of gastric s c a r r i n g a n d contracture with pyloric o b s t r u c t i o n is also to be anticipated. G a n d h i a n d R o b a r t s G a n a lyzed the phase of gastric obstruction. I n 11 instances, the average interval of s y m p toms of obstruction f r o m time of ingestion of ferrous sulfate was 4 weeks w i t h a r a n g e of 13 to 40 days. Five cases h a d p u r e pyloric stenosis resulting f r o m t h e d i r e c t corrosive action of ferrous sulfate on the gastric m u cosa. T h e r e m a i n i n g 6 c h i l d r e n h a d gastric stricture a n d in 2 instances h a d p y l o r i c stenosis as well. O n e child, in a d d i t i o n to a stricture, h a d a gastric ulcer p e n e t r a t i n g into the liver. At the Cook C o u n t y C h i l d r e n ' s H o s p i t a l in Chicago, Ill., 1,427 c h i l d r e n w h o ingested potentially poisonous substances were seen from Jan. 1, 1962 to J u l y 1, 1963, a n d the material involved in 20 instances Was iron. 7 One fatal a n d three severe cases of iron poisoning f r o m this g r o u p will be p r e s e n t e d and the t h e r a p y outlined. CASE R E P O R T S

Case 1. A. W., a 16-month-old Negro male was admitted to Cook County Children's Hospital at 2:15 A.~t. on Oct. 15, 1962, five days after he had taken 20 of his mother's ferrous sulfate tablets, size unknown. In the succeeding days he developed anorexia, fever, and lethargy; jaundice was noted on the day before admission. Physical examination revealed an acutely ill child with temperature of 103.8 ~ F., pulse rate of 140, respiratory rate of 40, and weight 10 kilograms. Sclerae and skin were markedly ieteric, and there was fetor hepaticus. The liver was firm and enlarged to 6 cm. below the right costal margin, and the spleen was palpable by 2 era. In spite of supportive treatment with intravenous fluids, tetracycline and oxygen, he died 12 hours later. On admission the complete blood count was: hemoglobin 4.2 Gm., red blood cells 1,500,000, white blood cells 102,000 (corrected 61,450) with 25 neutrophils, 21 band forms, 23 lymphocytes, 8 rnonocytes, 3 myelocytes, 20 metamyelocytes, and 65 nucleated red blood cells. Other laboratory reports were 2-plus urobilinogen in the urine, serum bilirubin 29 mg. per. 100 ml. indirect and 3.6 mg. per 100 ml. direct,, cephalin ttocculation 4-plus, thymol turbidity 4 units,

Ferrous sul[ate poisoning

2 19

gamma globulin turbidity over 3.2 Gm. per cent, and nonprotein nitrogen 67 mg. per cent. Significant autopsy findings were fatty infiltration and massive necrosis of the caudate and right lobe of the liver with hemosiderin deposited in the fibrous septa. There were hemorrhages and corrosive changes in the stomach and first part of the duodenum, leukemoid reaction in the bone marrow, and aspiration bronchopneumonia, s Case 2. M. P., a 23-month-old Negro female was admitted to Cook County Children's Hospital on Feb. 19, 1963, at 4:45 P.M. She had ingested a minimum of 25 to a maximum of 40 ferrous sulfate tablets, size unknown, that afternoon, and within one or two hours had begun vomiting black material streaked with blood and had passed several black liquid stools. Physical examination revealed an acutely ill, lethargic child with blood pressure 95/50, apical pulse 100, temperature 99 ~ F., and weight 10 kilograms. Fifteen minutes later she was comatose and unresponsive to stimuli. Gastric lavage was immediately begun by using 3.75 Gm. of sodium bicarbonate in tap water and continued until the black bloody return became clear. Another 3.75 Gm. of sodium bicarbonate and 45 c.c. of milk of magnesia were left in the stomach, and intravenous fluids were started. The serum iron level at this time was later reported .as 1,166 /zg per 100 ml. and the hematocrit was 43 per cent. A peritoneal catheter was inserted two and a half hours after admission, and peritoneal dialysis was begun with the use of a solution containing approximately 370 mOsm. per liter and electrolyte composition similar to plasma except for the absence of potassium. Dialysis solution in 400 c.c. amounts was intilled and withdrawn every 45 to 60 minutes. Attempts to use a larger volume seemed to significantly impair ventilation. Tetracycline was added to the intravenous fluids because of the possibility of aspiration during gastric lavage. Bloody emesis of about 200 c.c. occurred 11 hours after admission, and 200 c.c. of whole blood was given with stabilization of vital signs. Fifteen hours after dialysis was begun fluid began leaking from the site of the catheter insertion and limited instillation of dialysis fluid to 300 c.c. increments. This occurred even with the usual pursestring procedure as a pediatric catheter was not avilable and an adult catheter had to be used. The patient developed profound shock with



February 1964

blood pressure of 60/0, tachycardia of 168, and hematocrit of 67 per cent 40 hours after admission, but she improved following administration of 200 ml. of plasma. Calcium disodium EDTA, 350 mg., intramuscularly, every 12 hours for 10 doses was begun 2 hours later. The next day the patient developed signs of consolidation of the right middle lobe and the peritoneal fluid was cloudy. A Gram stain of the peritoneal fluid was interpreted as gram-positive diplococci; the intravenous antibiotic was changed to aqueous penicillin G, 5 million units per 24 hour periods, and the dialysis was discontinued. Ileus with abdominal distention which followed was relieved with continuous Levin suction and fluid and electrolyte replacement. The potassium at that time was 5.7 mEq. per 100 ml. so hypokalemia was not thought to be the etiology of the ileus. When gram-negative rods, later identified as Escherichia coli sensitive to chloramph~nico~ and colistin, were discovered in the d~alysance culture, intravenous antibiotic therapy was changed to chloramphenicol. By February 27 this patient had improved ehough to take fluids orally. The antibiotic was cOnfinukd~for a total of 8 days until March 4. Hbwever,: after chloramphenicol was stopped, fever, abdominal pain, and distention returned, and colistin was given, 25 rag. intramuscularly every 12 hours for 6 days. The patient (M. P.) was markedly improved by March 9 and continued to remain well. Urine culture grew Staphylocovcus aureus and enterococci, sensitive to nitrofurzntoin and with colony count over 105 on March 18, 1963, and nitrofurantoin was given orally on March 21 for 10 days.

Other treatment included: oxygen from the time of admission to February 27; antacid therapy with aluminum hydroxide gel from Febru. ary 20 to March 18; daily intravenous and then oral vitamins, and supportive nursing care. An upper gastrointestinal series was normal one month after admission, and the patient was discharged in good condition, apparently recovered. Laboratory data are summarized in Table I, and the most interesting data concerning dialysis and values of iron in serum, urine, and dialysance are to be found in Table II. Case 3. A. L., a 21-month-old Negro male was admitted to the Cook County Children's Hospital on May 21, 1963, at 11:00 P.M., 4 hours after ingesting an unknown number of iron and calcium tablets, probably less than 15, prescribed for his mother. The amount of iron contained was not known. Two and one half hours after ingestion he regurgitated about 10 tablets and then vomited twice more. Physical examination showed a child of 12 kilograms with temperature of 97 ~ F., blood pressure of 100/60, pulse of 120, and shallow respirations of 30 per minute. He was semistuporous but responded to pain. His pupils were miotic. The abdomen was soft with hyperactive bowel sounds. After digital rectal examination there was expulsion of a watery black stool. Deep tendon reflexes were not elicited. The patient was lavaged with sodium bicarbonate and given an enema of normal saline and sodium bicarbonate. An admission serum iron concentration was 463 gamma per 100 ml., the hematocrit was 33 per cent, carbon dioxide 10

T a b l e I. S u m m a r y of labo.ratory data, P a t i e n t M. P.

Date 2/20 2/21 2/22 2/23 2/25 2/26 2/27 2/28 3/1 3/4 3/5 3/7 3/11 3/22

BUN (rn~. % )

Na (mEq.)

Cl (mEq.)

K (mEa.)

CO~ (mEq.)

Prot. A / G (Gin. %)


97 99 95 91 94

5.2 8.1 5.7 5.7 3.2


22 52 13

130 135 131 136 139

4.2/2.4 5.2/2.6 4.4/2.8



6 7 9 11

135 128 131 128

85 90 89 90

5.3 4.3 3.7 4.3

Icterus index.... 6 10 14 10 10



12 10 4.0/3.9

Volume 64 Number 2

Ferrous sulfate poisoning

mEq. per liter, and nonprotein nitrogen 20 rag. per 100 ml. Intravenous fluids and oral aluminttm hydroxide gel were initiated. Calcium disodium EDTA was given, 450 mg., intramuscularly, every 12 hours, beginning 2 hours after admission. On May 22 at 7:15 a.~x. he was awake and crying. Vital signs had remained stable and he voided for the first time since admission. The urine contained 160 gamma iron per 100 mI., and a serum iron obtained shortly afterward was 181 gam.ma per 100 ml. The intravenous fluids were discontinued later that evening, but calcium disodium EDTA was continued for a total of 5 days along with oral vitamins and antacid treatment. A flat film of the abdomen showed contrast material remaining in the stomach and rectosigmoid areas even after two 500 e.c. enemas of normal saline on May 21. He was discharged on May 28 in good condition. Serum iron on May 23, thirty-eight hours after ingestion, was 65 gamma per 100 ml. and a urine at that same time contained 800 gamma iron per 100 ml. The iron binding capacity was 217 gamma per 100 ml. and total iron binding capacity 282 gamma per 100 ml. with 23 per cent saturation. The urinalysis was normal on May 23 except for 2-plus coproporphyrin III. Four serial liver profiles, including serum proteins, icterus index, cephalin flocculation, thymol turbidity, gamma globulin turbidity, and alkaline phosphatase, were normal. Hematologic studies showed: Hemoglobin 11.2 Gm., red blood cells 4.06 million, white blood cells 15,100 with a shift to the left. Case 4. A. H., a 17-month-old Negro male


Alkaline phosphatase (Bodansky units)

Cephalin ~.oeculation

Thymo! turbidity (Mac L. U.)

globulin turbidity (Grn. % )

1-plus 1-plus

3.0 3.4

1,10 0.85





2-plus 1-plus

3.8 5.0

1.20 0.90


1-plus 2-plus

4.4 6.8

0.70 1.20




was admitted to the Cook County Children's Hospital on May 22 at 7:15 P.M., 1 hour after ingesting 90 Mol-irort tablets (195 rag. ferrous sulfate per tablet). He had vomited spontaneously at least 5 times after taking the pills, and in the admitting pavilion he was lavaged and an universal antidote was instilled into his stomach. Admission examination revealed a child of 10 kilograms with apical pulse of 120 and respirations of 28. He was apparently in good health and showed no significant findings other than mild lethargy and the vomiting of clear material with dark flecks of blood. Maintenance intravenous fluids with 750 mg. of EDTA for 24 hours were started after obtaining an initial serum iron of 592 gamma per 100 ml. The child was placed in an oxygen tent and given 5 rag. of vitamin K1 oxide, intramuscularly, and oral aluminum hydroxide gel. Four hours after ingestion the child was very lethargic and difficult to arouse, but the blood pressure and other vital signs were stable. No diarrhea had occurred so he was given a normal saline enema. Fifteen hours p o s t ingestion he was still lethargic but Otherwise well, and a flat film of the abdomen did not show radiopaque material. A repeat serum iron at that time was 400 gamma per 100 ml. and the first urine was voided which contained 200 gamma of iron per 100 ml. By 28 hours he was alert but irritable, voiding and apparently normal. Another 750 mg. dose of intravenous EDTA was placed in the maintenance fluids for the next 24 hour period. Following this, fluids were given orally and EDTA was continued, 375 mg. being given intramuscu-



Hb ( Gra. )





9.7 30/9 18,400 7.5

22 1


2 2 2

February 1964


T a b l e II. S u m m a r y of dialysis d a t a a n d values of iron ~ in serum, u r i n e a n d dialysance Dialysis In (e.c.)


2/19 2/20 2/21 2/22 2/23 2/24 2/25


1,600 7,7OO 5,700 2,800

Out (c.c.)

1,500 6,085 L 5,440 L 2,500 L

Test (c.c.)

5,738]l 82 5,717 ~ 1,900e ~

Total Fent gamma test

24 H. Total U. Vol. Fev$ (e:c.) gamma

529.1 818.9 302.7

470 330

Fev T~ al % FeD % Fe. out % Fes.w test test ] gar, la gamma gamma gamma i, (calc.)



168 203

14.3 15.9

380 260

697.8 80.9 78.8

777.9 397.5


Total 1 7 , 8 0 0 15,525 L 13,355 1,750.7 ~ 1,873.2 Inter-relationships of iron in serum, urine and dialysanee: On 2/21/1963 and 2/22/1963 when simulta. neous serum, urine, and dialysance iron levels were obtained, 1175.4 gamma Fe was removed in dialysance (calculated) and 640 gamma Fe was excreted in the urine. Fe was removed in dialysance, 697.8 gamma calculated, even before calcium disodium EDTA was given. This chelating agent increased the iron removed in dialysance by at least 55% even in the presence of a normal serum iron level. eFe determinations by laboratory of R.


Dern, M . D . , tIektoen_Institute for Medical Research, Chicago, Ill.

e~2/21 a n d p a r t of 2/20




-~a"~discontinued at 5 : 0 0 P.M. (peritonitis)



C a l c i u m disodium E D T A begun a t noon

tFeD ~

Total g a m m a or g a m m a % Fe in dialysance

+Feu - - Total g ~ m m a or g a m m a % Fe in urine

larly every 12 hours for 6 doses. Aluminum hydroxide gel was continued at intervals of 4 hours and vitamins were given daily. A serum iron at 40 hours was 10 gamma per 100 ml. and at 64 hours was 9 gamma per 100 ml. with iron binding capacity of 364 gamma per 100 ml., total iron binding capacity of 373 gamma per 100 ml., and saturation of 2 per cent. Other laboratory tests were: normal urinalysis on May 23; hemoglobin of 5.4 Gm. per 100 ml., red blood cells 3.44 millions, and white blood cells 8,600 with normal differential. There were 3-plus hypochromia, 1-plus microcytosis, and 2-plus anisocytosis noted. The hemoglobin rose to 6.1 Gm. on May 28 and 6.8 Gm. on May 31. Liver profiles, including those noted in Case 3, were borderline normal on 5 different occasions. Electrolytes and blood urea nitrogen were normal except for a carbon dioxide of 19.5 mEq. on May 23. His course was uneventful, and he was discharged on June 4 to return for readmission on June 28. At this time there were no symptoms, and the physical examination was normal. Hemoglobin was 8.5 Gm. per 100 ml., red blood cells 5.04 millions, white blood cells 12,400, and differential normal except for 7 per cent eosinophils. There was 3-plus hypochromia, 2-plus anisocytosis, and 1-plus microcytosis. Liver profile and upper gastrointestinal series were both normal.

serum Fe

~[L z

U n k n o w n a m o u n t of leakage


and p a r t of 2/20



T h e t r e a t m e n t of iron poisoning by means of chelation with E D T A is well grounded. Theoretically, this chelating agent should form a soluble, relatively nonionizable, not too toxic c o m p o u n d in its combination with iron a n d thus be available for excretion. E x p e r i m e n t a l l y , calcium has been shown to be less strongly b o u n d to E D T A t h a n iron2 I n fact, this was shown to be true clinically by Wishinsky a n d his co-workers 1~ who used calcium d i s o d i u m E D T A to mobilize and remove iron in a n a d u l t with hemochromotosis. T h e i r patient's excretion of iron was 1.2 nag. per day or almost 4 times normal. W i t h daily intravenous administration of the chelating c o m p o u n d this baseline excretion of i r o n was increased threefold. The only u n t o w a r d effect was a rapid fall in p r o t h r o m b i n activity. Bronson a n d Sisson11 d e m o n s t r a t e d i n dogs severely intoxicated with iron t h a t calcium disodium E D T A lowered serum iron concentration a n d prolonged survival time. O n e case of iron poisoning in a child was m a n a g e d with this agent but the child died 60 hours after ingestion of the iron. 12

Volume 64 Number 2

Two children with severe iron poisoning recovered when Schafir 13 first successfully used the recommended one dose calcium disodium E D T A treatment of 80 rag. per kilogram, one half the dose being given intravenously and one half orally after removal of as much ferrous sulfate f r o m the gastrointestinal tract as possible and administration of oral sodium bicarbonate to form an insoluble iron compound. The initial serum iron level in the first case was 6,080 g a m m a per 100 ml. and by the fourth day had decreased to 320 g a m m a per 100 ml. T h e only urine value obtained was 90 g a m m a iron per 100 ml. on the eleventh day when a simultaneously obtained serum iron was 256 gamma per 100 ml. Schafir's second case had a first day serum iron level of 373 g a m m a per 100 ml. which decreased to 200 on the second day when the urine iron was 217 gamma per 100 ml. Another child was successfully treated by Barrie and Wilson? 4 The initial iron level was 4,840 g a m m a per 100 ml. and 36 hours after admission the value had declined to 137. Very significantly, they demonstrated that when all recorded cases of iron poisoning that had serum iron levels reported were graphed, the levels followed the same pattern regardless of treatment. T h a t is, a steep decline in serum iron occurred in 36 hours with the lowest levels present in the patients treated with EDTA. Data on urine iron concentration in cases of poisoning are limited to the previously mentioned instances in man. Foreman and co.workers15 showed t h a t excretion of radioactive iron in the rat was doubled by chelating agents. From the aforementioned evidence it is logical to conclude that the use of calcium disodium E D T A is of great value in the treatment of acute iron poisoning. "However, when this is used as the only means of removal of absorbed iron, the sole avenue of excretion is by way of the urine. Since the first two phases of shock m a y compromise blood flow to the kidney and reduce urine volume, it becomes evident that this mode ;of excretion will be impaired. Furthermore, since there is a sharp decline in serum iron

Ferrous sul[ate poisoning

2 23

within 36 hours regardless of treatment, it is quite likely that this represents diffusion into tissue. Thus, a single dose of 500 rag. of intravenous calcium disodium E D T A as recommended may not be enough to chelate all the excess iron present. There are theoretical objections to the oral use of this compound as the chelate is soluble and m a y be partially ionizable. Thus, an additional potentially toxic quantity of iron might be absorbed through the intact lower small bowel. Other methods with or without the use of E D T A have been tried or suggested to remove absorbed iron after acute poisoning. Amerman, Brescia, and Aftahi ~a in 1958 used exchange transfusion in treating a child who recovered as did WeichseW in 1962. Combined chelation, hemodialysis, and alkaIinization as a treatment for iron poisoning was suggested by Felts, Barringer, and Meridith is on the basis of in vitro experiments. They found it possible to dialyze ferric ammonium citrate from saturated reservoirs and recoveries were 25 and 57 per cent of added iron. When calcium disodium E D T A was infused directly into the reservoirs, the yield was increased to 44 per cent and 69 per cent after 4 hours of dialysis. Under ideal conditions, in severe iron poisoning when urine flow is markedly reduced, intravenous calcium disodium E D T A and hemodialysis appear to be the treatment of choice in removing absorbed iron. However, this is not readily available except in large medical centers, and precious time in early critical hours after iron poisoning is consumed in setting up this procedure. Peritoneal dialysis suggests itself as a simple, almost universally available technique for removal of iron. D a t a from Case 2 tabulated previously show that a significant amount of iron was removed by dialysis alone in the first 40 hours. After administration of intramuscular calcium disodium EDTA, the concentration of iron in dialysance was increased by 55 per cent even in the presence of a normal serum iron level. On February 21, when serum, dialysance, and urine iron levels were simultaneously obtained, the calculated total dialysance


February 1964


iron was twice that of urine. This suggests that 3 times as much total iron might be removed by using peritoneal dialysis in conjunction with calcium disodium E D T A as could be removed by chelation and urinary excretion alone. Putnam 19 first suggested the use of the living peritoneum as a dialyzing membrane. Interestingly, he found that of substances used intravenously in experimental animals, ferrocyanide was second only to sodium iodide in diffusing rapidly and completely through the peritoneum. By t950 there were 101 cases of peritoneal dialysis, 2~ in the literature, instituted for various indications including prolonged anuria from heavy metal poisonings but not for the purpose of removing the poison. This procedure was used in conjunction with BAL for bichloride of mercury poisoning as early as 1948, the indication beiffg prolonged anuria and uremia, and the patients recovered. 21' 22 In view of the dialysance data obtained in Case 2 one wonders if significant amounts of the bichloride of mercury might have been removed by this route. It is well to note in the series of 101 cases analyzed by Odell, Ferris, a n d Power, 2~ continuous lavage seemed to be associated with a higher percentage of recoveries as well as a higher incidence of secondary peritonitis than intermittent peritoneal dialysis, although the number of cases in each group was not comparable, and definite conclusions could not be reached. The other complication encountered was pulmonary edema which was related to the composition of the dialyzing fluid, although hypoproteinemia might have been a factor. In support of the observation that hypoproteinemia is an important complication of peritoneal dialysis, Etteldorf 23 observed a loss of 3.8 Gm. albumin for every 2,000 c.c. of dialysis solution used in one series, or roughly 0.2 Gm. per 100 ml. H e cautioned that a careful check of serum proteins is required during dialysis, and replacement with intravenous albumin may be needed. Etteldorf also established a rational basis for choice of composition of dialysis fluid by using the patient's serum

osmolarity as the lowest limit for osmolarity of solution to be used in dialysis. Thus, the dreaded complication of pulmonary edema may be prevented. Either an osmometer can be used to directly determine this, or it can be calculated by the following formula: serum osmolarity = mOsm. serum water/kilo. gram = Na in mEq./L, x 2 plus (BUN rag. per cent x 10/28) plus (glucose rag. per cent • lo/18o).

The commercial solutions, Inpersol, Peridial and Dianeal alI contain approximately 370 mOsm. per liter when in 1.5 per cent dextrose. This type of solution should be safe in most clinical situations if the patient's serum osmolarity is below 350. If a dehydrating effect is needed, the same solutions in 7 per cent dextrose offer 670 mOsm. per liter. From a review of recorded cases, including the four cases presented, one can enumerate four phases of reaction to severe acute ferrous sulfate poisoning and possibly predict a fifth phase not yet demonstrated, as follows: I. Hemorrhagic gastroenteritis occurring one-half to one hour or more after ingestion; this m a y be accompanied by shock, acidosis, coagulation defects, and coma. II. Delayed profound shock presenting itself 90 to 48 hours after ingestion. I I I . Liver injury and failure not previously mentioned as a sole cause of death and illustrated by Case 1. IV. Gastric obstruction occurring at an average of 4 weeks post ingestion with a range in previous cases of 13 to 40 days. V. Theoretical phase of cirrhosis due to subfatal liver damage is possible but has not been reported as occurring from acute iron poisoning. Comprehensive management of these problems m a y be involved and time consuming. T h e reaI hallmark of treatment is prevention. It might be wise to educate the laity by encouraging the labeling of adult ferrous sulfate or other iron preparations with a reminder, "poison to children.

Volume 64 Number 2

Therapy could be s u m m a r i z e d in this m a n ner: 1. Induce emesis w i t h p a t i e n t in prone position and neck flexed to p r e v e n t aspiration, and then initiate g a s t r i c l a v a g e with sodium bicarbonate. L e a v e a solution of sodium bicarbonate a n d a saline c a t h a r t i c in the stomach. 2. Intravenous fluids should b e given as soon as possible a n d should c o n t a i n i n t r a venous calcium d i s o d i u m E D T A , 50 to 75 nag. per kilogram p e r d a y d i v i d e d into two doses to chelate all possible free a b s o r b e d iron. After the second shock p h a s e is passed, tfiis compound m a y be given i n t r a m u s c u larly for a total of 4 o r 5 days. T h i s agent should be a d m i n i s t e r e d even in the absence of symptoms if there is a w e l l - d o c u m e n t e d history of ingestion of one o r m o r e g r a m s of ferrous sulfate o r the a m o u n t is u n k n o w n . Calcium disodium E D T A should be continued until serum i r o n or u r i n a r y iron values are known, if t h e y c a n be o b t a i n e d readily or until 48 hours have elapsed since the time of poisoning a n d second phase symptomatology has Ilot occurred. 3. Blood, plasma, a n d vasopressors in a d dition to intravenous fluid r e p l a c e m e n t a n d supportive measures should be used for any sign of cardiovascular collapse. 4. Peritoneal o r hemodialysis m a y be considered in a d d i t i o n to the a f o r e m e n t i o n e d measures if severe first phase s y m p t o m s are present and urine flow is g r e a t l y r e d u c e d or absent. 5. Intravenous a n d oral v i t a m i n s m a y help to prevent liver d a m a g e , a n d oxygen may afford f u r t h e r p r o t e c t i o n d u r i n g the first 48 hours after poisoning. 6. L a b o r a t o r y d e t e r m i n a t i o n s should include serum proteins w h e n dialysis is used, routine electrolytes to guide in m a i n t e n a n c e fluids and t r e a t m e n t of a c i d o s i s , liver function tests to detect signs of h e p a t i c injury, and at least a serum iron d r a w n on a d mission. 7. U p p e r gastrointestinal series at 4 weeks even in the absence of gastric o b s t r u c t i o n is to be strongly r e c o m m e n d e d to rule out peptic ulceration or d a m a g e to the s t o m a c h

Ferrous sul[ate poisoning


or d u o d e n u m . L a p a r o t o m y should be considered if persistent v o m i t i n g occurs any time after the second week post poisoning a n d an u p p e r gastrointestinal series corroborates the diagnosis of obstruction. E a r l y and continuous a n t a c i d a n d d i e t a r y t h e r a p y m a y help in p r e v e n t i o n of this complication.

Cases 1 and 4 were from the service of Dr. Joseph Greengard, Chairman of the Department of Pediatrics, and Dr. Matthew Lewison. Case 2 was from the service of Dr. Rowine Hayes Brown, and Case 3 was from the service of Drs. Ira M. Rosenthal and Ronald B. Mack. These attending pediatricians kindly permitted publication of the aforementioned cases. Dr. Paul Szanto, Chairman of the Department of Pathology, kindly permitted publication of the autopsy findings of Case 1.


1. Hoppe, J., Mercelli, G., and Tainter, M.: A review of toxicity of iron compounds, Am. J. M. Sc. 230: 558, 1955. 2. Reissmann, K., Coleman, T., Budai, B., and Moriarty, L.: Acute intestinal iron intoxication. I. Iron absorption, serum iron and autopsy findings, Blood 10: 35, 1955. 3. Nineteenth Ross Pediatric Research Conference, p. 53, 1956. 4. Committee on Toxicology: Accidental iron poisoning in children, J. A. M. A. 170: 676, 1961 (editorial). 5. Aldrich, R.: Acute iron toxicity, in Iron in clinical medicine, Berkeley, 1958, University of California Press.. 6. Gandhi, R., and Robarts, F.: Hour glass stricture of the stomach and pyloric stenosis due to ferrous sulfate poisoning, Brit. J. Surg. 49: 613, 1962. 7. Brown, R. H., Assistant Medical Superintendent of Cook County Hospital in Charge of the Children's Division: Unpublished. 8. Szanto, P., Chairman of Department of Pathology of Cook County Hospital: Performed autopsy and presented C.P.C. on Jan. 25, 1963. 9. Martel, A., and Calvin, M.: Chemistry of metal chelate compounds, New York, 1952, Prentice-Hall, Inc. 10. Wishinsky, H., Weinberg, T., Prevost, E., Burgin, B., and Miller, M.: Ethylenediaminetetraacetic acid in the mobilization and removal of iron in a case of hemachromatosis, J. Lab. & Clin. Med. 42: 550, 1953. 11. Bronson, W., and Sisson, T.: Studies on acute iron poisoning, A. M. A. J. Dis. Child. 99: 19, 1960.



12. Cann, H., and Verhulst, H.: Accidental iron poisoning in young children--the hazards of iron medication, A. M. A. J. Dis. Child. 99: 688, t960. 13. Schafir, M.: The management of acute poisoning by ferrous sulfate, Pediatrics 27: 83, 1961. 14. Barrie, I-t., and Wilson, B.: Calcium disodium edathamil in the treatment of ferrous sulfate poisoning, J. A. M. A. 180: 244, 1962. 15. Foreman, H., Huff, R., Oda, J., and Garcia, J.: Use of a chelating agent for accelerating excretion of radioactive iron, Proc. Soc. Exper. & Biol. Med. 79: 520, 1952. 16. Amerman, E. C., Brescia, M., and Aftahi, F.: Ferrous sulfate poisoning, report of a case sltccessfully treated by exchange transfnsion, J. PEDIAT. 53: 476, 1958. 17. Jacobziner, H., and Raybin, H.: Accidental chemical poisoning. Iron intoxication, New York J. Med. 62: 85, 1962. t8. Felts, J., Barringer, M., and Meridith, J.: Combined chelation, hemodialysis and alka-

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linization. A possible treatment for iron pol. sorting, Tr. Am. Soc. Artif. Int. Organs 8: 229, 1962. Putnam, T.: The living peritoneum as a dialyzing membrane, Am. J. Physiol. 63: 548, 1922. Odell, H., Ferris, D., and Power, M.: Peritoneal lavage as effective means of extrarenal excretion, Am. J. Med. 9: 63, 1950. Batson, R., and Peterson, J.: Acute mercury poisoning: treatment with B.A.L. and in anuric states with continuous peritoneal lavage, Ann. Int. Med. 29~ 278, 1948. Toth, J., and King, I-Ix The treatment and cure of bichloride of mercury poisoning by the use of peritoneal lavage, Ohio State M. J. 44: 1013, 1948. Etteldorf, J., Dobbins, W., Sweeny, M., Smith, J., Whittington, G., Sheffield, J., and Meadows, R.: Intermittent peritoneal dialysis in the management of acute renal failure in children, J. PEDIAT. 60: 327, 1962.