Boric Acid Poisoning: Report of 11 Cases L

1018 WONG A..D OTHEI.s: Boiuc Acw PoIso.m.G April 25, 1964, VOL 90 Boric Acid Poisoning: Report of 11 Cases L. C. WONG, M.D.,* M. D. HEIMBACH, M.D4 D. R. TRUSCOFI', M.D4 and B. D. DUNCAN, M.D.,§ Regina, Sask.

SOMMAIRE Les auteurs rapportent 11 cas d'intoxication .i l'acide borique dans une pouponni.re et r6sultant de l'emploi accidentel ou par inadvertance d'une solution d'acide borique . 2.5% dims la pr6paration des aliments pour b.bSs. Cmq des nourrissons sont morts. A l'exception de deux, tons pr6sentaient le tableau classique de l'intoxication aiguii & 1'acide borique, soit diarrh6e, vomissement, 6ryth.me, exfoliation et desquamation de la peau et forte irritation du syst.me nerveux central. Les premi.res manifestations de l'empoisonnement d6taient pas sp&ifiques et un enfant mourut avant que n'aient apparu les signes cutan.s. La dialyse intrapfriton6ale, appliqu.e dans 9 cas, s'est r6v6l.e le traitement le plus efficace. L'acide borique, dont Ia valeur th.rapeu- tique est du reste douteuse, devrait .tre enti.rement .limin6 des h.pitaux, des dis- pensaires et m6me de la pharmacop6e. Canad. Med. Ass. J. April 25, 1964, vol. 90 WONG AND (YrHERS: Bomo Acm POISONING 1019

TABLE I.-CLINxc. MANIFESTATIONS AND LABORAToRY FINDINGS IN BORIC Acm POISONING ______Clinical features ______Serum electrolyte levels ______Amount of Vomiting Oliguria Case borate and Bleed- and Sodium Potassium Chloride Bicarbonate Urea Borate No. ingested (g.) Skin diarrhea CNS ing anuria (mEq./l.) (mEq./l.) (mEq./l.) (mEq./l.) (mg.%) (mg.%) Survival 1 14.06 - ++ + - + 153 7.0 118 - 52 160 2days 2 6.25t + ++ +++ ++ + 158 4.4 112 11.4 - 40 3 days 3 9.25t +++ +++ +++ - + 176 - 122 13.3 31 100 3 days 4 4.5t +++ +++ +++ - + 153 4.9 102 20.0 - 20* 3 days 5 12.5 +++ +++ +++ + + 153 6.1 110 21.0 56 100 3days 6 4.5 ++ ++ ++ - + 155 4.8 112 20.7 29 14t 2.years+ 7 2.25 ±± ++ ++ - + 148 3.9 105 18.0 19 6t 2.,iyears+ 8 3.0 ++ ++ + - + 163 5.2 112 19.0 17 15 2.years+ 9 3.0 ++ ++ + - + 160 4.9 115 19.0 20 10 2.years+ 10 4.0 ++ ++ + - + 160 5.0 115 20.0 40 8t 2.years+ 11 2.0 - + - - - 150 4.0 111 - 8 2 2Y.years+ *T.en post mortem. tTsken after dialysis.

16, 1961, when she developed diarrhea and vomiting. The skin around the mouth, under the chin, and on the Her stools and vomitus were greenish with mucus. She abdominal wall, perineum and buttocks was markedly was very active and cried excessively. erythematous, as if she had been very close to an open Laboratory findings revealed a serum bilirubin of fire. Her respiration was rapid but deep. She tended 8.5 mg. %; serum electrolyte levels are recorded in to arch her back and to stare, was extremely irritable Table I. and had an exaggerated Moro reflex. Initially milk allergy was diagnosed and her formula Laboratory findings are recorded in Table I. was changed to Sobee. Vomiting and diarrhea persisted, Because of the striking skin lesions, boric acid and she became quite lethargic 12 hours later. Because poisoning was immediately suspected. Gastric lavage of the development of similar gastrointestinal upset in was performed and the contents of the stomach, as well two other newborn infants in the same nursery, an as a blood sample, were submitted to the provincial infectious type of gastroenteritis was considered. Stool toxicology laboratory for identification of possible culture was taken and subsequently reported negative. poison. Blood was also taken for estimation of serum About 20 hours after the onset of diarrhea and vomiting, electrolytes. An intravenous infusion of 5% glucose in she started to twitch and become drowsy. An intra- water was started. An exchange transfusion with 500 venous infusion of 5% dextrose in water was started and ml. of whole blood was performed 12 hours after the shortly thereafter her respirations ceased, 21 hours after onset of symptoms, i.e. 24 hours after initial ingestion the onset of symptoms. At no time did her skin show of boric acid. The general condition of the infant erythema or exfoliative dermatitis. At the time of death, deteriorated rapidly. The erythema of the skin became signs of boric acid poisoning became apparent in other generalized, and most of the lesions assumed the ap- infants in the same nursery; blood was therefore taken pearance of exfoliative dermatitis. A gentle touch of for determination of the boric acid concentration, the skin resulted in peeling of the whole thickness of which was 160 mg. %. Distilled water used for making epidermis. formula for this infant was then found to be 2.5% boric the The infant's eyes were bloodshot and acid solution. opisthotonus became severe. She appeared less toxic Postmortem examination revealed extensive hemor- after the exchange transfusion, and serum electrolytes rhages, congestion and edema of the lungs. The kidneys and borate level showed some improvement (Table II). were also congested microscopically and there was Oliguria developed and vomiting persisted. considerable swelling of the epithelium of the convo- Because of further deterioration, a second exchange luted tubules. The bladder mucosa was edematous and transfusion was started six hours after the first trans- showed areas of hemorrhages. The brain showed ex- fusion. Special precautions were taken to guard against tensive vascular congestion with widespread pen- hypocalcemia and cardiac arrythxnias during the pro- vascular hemorrhages and intravascular thrombosis. cedure. The infant had several episodes of convulsions and apnea, and the transfusion had to be abandoned Comment: Diarrhea, vomiting, lethargy and jaun- after 200 ml. was exchanged. Peritoneal dialysis using dice are non-specific manifestations of many dis- the modified technique described by Segar6 was started in an effort to reverse the rapidly deteriorating clinical orders in the newborn period, and the symptoma- course. Frequent convulsive and apneic episodes tology in this case provided no clue to the final per- diagnosis of boric acid poisoning. TABLE 11.-SERUM ELECTROLYTE LEVELS AFTER EXCHANGE CASE 3.-A full-term infant girl weighing 7 lb. 2 oz. TIIANSFUSTONT was born on March 13, 1961. She was fed a formula Sodium Potassium Chloride Bicarbonate of evaporated milk, and was well until the evening Case No. (mEq./l.) (mEq./L) (mEq./l.) (mEq./L) of March 16, 1961, when she developed diarrhea and 3. 145 4.0 87.5 17.2 vomiting. The stools and vomitus were greenish but 4. 152 4.6 91.3 19.0 contained no blood. 5. 153 6.1 100 .0 21.0 6. 150 40 95.0 21.0 Physical examination revealed a moderately dehy- 7. 148 3.9 97.5 17.2 drated infant with a flushed face and cherry-red lips. 10. 145 3.7 102.0 18.4 Canad. Med. Ass. 3. 1020 WONG AND OTHERS: Boiuc Acm POISONING April 25, 1964, vol. 90 sisted and she became comatose. Exfoliation of the skin Comment: This case illustrates the favourable became generalized, and desquamation was noted in consequence of peritoneal dialysis in boric acid many areas of the body. The mucous membranes and intoxication. nail beds were also involved. She remained anuric. The infant died 10 hours after the institution of pen- CASE 11.-An infant girl born on March 13, 1961, toneal dialysis. was alleged to be full-term but weighed only 4 lb. 2 Postmortem examination revealed widespread vascu- oz. Apart from the small size of the baby, physical lar congestion with fresh hemorrhages on the surface examination at birth was negative. She was started on and in the substance of the lungs, in the epicardium, Enfalac formula but regurgitated part of her feeding leptomeninges, brain substance and mucous membranes on each occasion. A stomach tube was passed and en- of the alimentary canal and urinary bladder. There countered no obstruction. was pronounced edema of the bladder mucosa and the On March 18, 1961, the colour of her emesis and lungs. Degenerative changes were seen in the paren- stools was noted to be greenish and like that found chymal cells of the liver, kidneys and adrenals, in myo- in the infants who had been accidentally poisoned. cardial fibres and in neurones of the brain. Mild regurgitation and loose bowel movements persisted for three days. Her skin was normal, and there Comment: This case exhibited all the classical were no abnormal neurological signs. manifestations of acute boric acid poisoning. The Laboratory findings are recorded in Table I. Blood and urine were submitted for identification of amount of boric acid ingested was believed to have borate. The plasma showed only a trace of borate far exceeded the lethal dose. which was measured as less than 2 mg. %. The possi- bility that the sample had become contaminated, be- CASE 9.-A full-term infant girl was born on March cause numerous specimens had been sent to the la- 9, 1961. She was perfectly normal, was fed an evapor- boratory within such a short period of time, was con- ated milk formula and was discharged from the nursery sidered. A second sample of blood was withdrawn six on March 15, 1961. It was the custom of the nursery hours later, and no trace of borate was found. How- to discharge a bottle-fed newborn infant home with ever, urine showed a positive tumenic paper test for a supply of that day's formula. boric acid, and urinary excretion of borate continued After discharge from hospital, she took 4 oz. of the for 17 days. formula which was obtained from the hospital. Shortly Because of the mildness of her symptoms and the after the feeding, she developed retching, vomiting low plasma borate level, peritoneal dialysis was and loose stools. The vomitus and stools were greenish. considered unnecessary. An intravenous infusion was The mother also noted the sore and red buttocks and started and the urine output was watched closely. The perineum. At this time the other eases of 'boric acid general condition of the 'baby remained good. Intra- poisoning had been discovered and this diagnosis was venous infusion was discontinued after three days. suspected in this case. The infant was readinitted, After that she took feedings well and gained satis- for observation and investigation, on March 17, 1961. factorily. She was discharged 32 days after birth, On admission the infant was listless and periodically weighing 5 lb. 10 oz. gave a high-pitched irritable cry. She was mildly de- Since discharge the patient has been examined regu- hydrated, with dry and red lips. The perineum and larly. At four months developmental delay was ap- buttocks were excoriated. Physical examination was parent. A pneumoencephalogram revealed marked otherwise negative. cerebral atrophy, the cause of which is obscure. An intravenous infusion of hypotonic solution of a mixture of 5% dextrose in water, 5% dextrose in saline Comment: The mild degree of poisoning (mini- and M/6 sodium lactate was given. Because of the mal clinical manifestations) with 'low plasma borate difficulties experienced with exchange transfusion in level would not explain the serious sequelae in this the other infants, it was decided to proceed with peri- child. toneal dialysis instead. Peritoneal dialysis was continued for 24 hours, and halfway through the procedure her DIscussIoN level of sensorium improved and she was much more restful. Phenobarbital, which had 'been used repeatedly I. CLINICAL MANIFESTATIONS to relieve her irritability, was no longer necessary. She Symptoms and Signs started to void at the completion of the dialysis, and The typical clinical picture of acute boric acid was able to retain small amounts of water. The skin poisoning begins with persistent vomiting. Even in lesions improved. small infants, considerable retching is found. In On her third day, diuresis began and it was necessary to increase the daily intravenous intake until our series, projectile vomiting was not noted, and intravenous fluids were discontinued on the 7th hospital the bluish-green colour of the vomitus was a con- day. The rest of her convalescence was complicated stant finding. Loose bowel movements occurred in by gaping of the abdominal wound where the stab all cases, and the colour of the stools was the same incision for dialysis had been made. Extensive de- as the vomitus. It was this peculiar colour of the squamation was noted for many days. emesis and stools which caught our attention and The concentration of borate in urine was measured led to the discovery of a mild case. Mucus was daily. The level declined gradually but borate was still noted in the stools in many of the cases. Bloody detectable in 1 mg. % on the 17th hospital day. diarrhea, which has been described in many re- She was discharged on the 25th day. Her subsequent ported cases, was seen in only one infant who growth and development have been normal. passed pure blood per rectum at the terminal stage. Canad. Med. Ass. J. April 25, 1964, vol. 90 WONG AND OTHERS: Bomc Acm POISONING 1021

Shortly after the onset of poisoning, the skin Laboratory Findings signs appear. Initially an erythema was noted Serum electrolyte determinations revealed hyper- around the mouth and on the buttocks and per- natremia, hyperchloremia and metabolic acidosis in ineum. It may resemble an irritation of the skin all cases and hyperkalemia in two cases. Blood pH caused by rubbing on the linen or a diaper rash. was measured in two cases and reported as 7.17 Soon erythema became extensive until the entire and 7.29. A slight elevation of blood urea was noted body looked like a "boiled lobster" (Fig. 1). The in two cases. Plasma borate levels paralleled the amount of boric acid ingested, the high values being among the fatal cases. Routine urinalysis was done in all cases except those in which death occurred during the anuric stage. Mild albuminuria was found initially but cleared up subsequently. All showed a positive tumeric paper test for boric acid. Excretion The concentration of borate in urine was recorded daily in all patients who survived. Because of extensive skin lesions of the perineum, it was not feasible to collect 24-hour urine for quantitative determination. Concentrations of 100 mg. % were found in the first 24 hours of poisoning in three instances (Cases 4, 5 and 6). Borate in decreasing

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S 10 15 20 25 DAYS AFTER INJECTION Fig. 3.-Urinary borate excretion in case 11. amounts was found in the urine for 20 days after ingestion in four patients (Cases 7, 8, 9 and 10) and for 23 days in one (Case 11). Data obtained from Case 11, who was treated conservatively, gave an opportunity to study the natural excretion of a small amount of ingested boric acid (Fig. 3). Al- though the plasma borate level was small, the excretion required a prolonged peried. Our findings are contrary to those obtained from experimental animals which show that a large quantity of borate is excreted in the first 24 to 48 hours. Furthermore, there is some evidence to suggest that the excretion of boric acid can be com- plete although the damage to tissues, if extensive, may be irreversible."2

II. DIAGNOSIS The diagnosis of acute boric acid poisoning is not difficult when the history of exposure is known and the characteristic skin lesions are present. It can be confirmed by demonstration of borate in Canad. Med. Ass. 3. 1022 WONG AND oni.s: Bomc Acm POISONING April 25, 1964, vol. 90

blood, cerebrospinal fluid, urine and tissues. The Exchange Tramrfusion simplest diagnostic test for borate is the tumeric Boric acid is readily absorbed by the gastro- paper test, which is performed by dipping tumeric intestinal tract and distributed throughout the body paper into the test solution strongly acidified with tissues.8-11 Recovery of the patient depends hydrochloric acid. The tumeric paper upon drying upon turns a pink to red colour. This may be confirmed the ability of the kidneys to excrete the toxic by placing a drop of ammonia water on the paper substance before it causes irreversible damage to and observing the transient occurrence of a blue- tissues. Patients so poisoned are invariably olignric black colour. Goldbloom and Goldbloom7 have or anuric and therefore incapable of eliminating adapted the test to a semiquantitative use by com- the poison without other aids. Exchange trans- paring the colour produced by various dilutions. fusion has been used for this purpose. Boggs and We found this method reliable only when the boric Anrode4 reported a 12-day-old infant with boric acid levels were less than 15 mg. %. Boric acid acid poisoning who was successfully treated by may also be determined quantitatively by titration exchange transfusions. As they stated, "It would and spectrographic or fluorescence measurements. seem reasonable that exchange transfusions would When skin lesions are absent, the diagnosis can be more helpful in a patient where the agent had be very difficult. Our first and fatal case presented been in the body for a relatively short period of a non-specific symptom-complex common to a time than if large quantities had been absorbed variety of disorders in the newborn period. If there over a long period of time." But exchange trans- had been no other infants with characteristic skin fusion is a laborious procedure not without danger, lesions suggestive of acute boric acid poisoning, the and we agree with Segar6 that the efficiency of this diagnosis would not have been made. Goldbloom procedure in the treatment of acute boric acid and Goldbloom7 stated that many milder cases of poisoning is limited. In our series, exchange trans- boric acid poisoning go unrecognized. We support fusions, using 500 ml. whole blood in each instance, their view and also suggest that some of the so- were carried out in six cases. We encountered not called "sudden deaths" due to gastroenteritis in the only practical difficulties in performing mass ex- newborn may be due to boric acid poisoning. A change transfusions simultaneously, but also many high index of suspicion is necessary when dealing undesirable and deleterious reactions on the part with the very young, and poisoning should, there- of the seriously ill infants. Throughout the pro- fore, be included in the differential diagnosis of cedure, intermittent vomiting, twitching and/or illnesses of the newborn even when the environ- frank convulsions persisted; cardiac irregularities ment is considered safe. which progressed even to cardiac arrest occurred. There is no definite lethal dose of boric acid. The effect of exchange transfusions on serum The pertinent data obtained from experimental electrolyte values is shown in Table II. In two cases animals varied from one species to the other.8 In there was apparent improvement in the electrolyte human beings, the lethal dose is even more un- levels while in the other four there was no signffi- certain. In the fatal group reported by Young, cant change. Serial determination of the plasma Smith and MacIntosh3 the amount ingested by borate level was performed in Case 3, which each infant was less than 3 g. There is no doubt showed a drop from 100 mg. % to 85 mg. % after that young infants are particularly susceptible to Jhe second 200-ml. exchange. The efficiency of ex- boric acid as poison. change transfusions in decreasing a high plasma borate level is clearly far from adequate. There III. MANAGEMENT was no clinical improvement in any of the infants There is no antidote for boric acid poisoning. after exchange transfusion. The general principles of management of poisoning caused by water-soluble agents are the removal Peritoneat Dialysis of a poison as quickly as possible and the institution Peritoneal dialysis has recently gained in popu- of supportive therapy. laxity in the treatment of acute renal failure, salicylate poisoning, salt poisoning and boric acid Gastric Lavage poisoning. In small infants, its efficiency, simplicity and safety have been demonstrated by Miller and Removal of gastric contents is necessary in Finberg12 and Finberg, Kiley and Luttrell'8 in the management not only for identification of the treatment of salt poisoning, Segar6 in boric acid poison but also for prevention of further absorp- poisoning, and Etteldorf et aL14 in salicylate poison- tion. This should be carried out in all cases, even ing. Furthermore, in a sudden disaster with many when the condition is not recognized until many cases to be treated simultaneously, mass peritoneal hours after the ingestion of the poisonous agent. dialysis can be instituted rapidly and can be kept In one of our cases, the concentration of borate in continuous for a long period. the stomach contents, removed 24 hours after the Peritoneal dialysis was instituted in nine cases. 'last dose of boric acid, was 125 mg. %. The results are summarized in Table III. The Canad. Med. Ass. J. D A fl April 25, 1964, vol.90 WONG ANI. OTHERS: nORIC t.CID rOISONING ±u.o

TABLE 111.-RESULTS OF PERITONEAL DIALYSIS Borate Amount of Serum electrolyte level after dialysis Volume of concentration borate dialysis in drainage removed Sodium Potassium Chloride Bicarbonate Borate Case No. fluid (ml.) fluid (mg.%) (mg.) (mEq./l.) (mEq./l.) (mEq./l.) (mEq./l.) (mg.%) 2.200 22 - 44 3.900 35 315 163 5.0 85 21 70 4.950 11 104.5 162 4.7 - 36 - 5.1800 10 180 150 4.6 81 21 - 6.4800 8 384 163 3.6 100 27.7 14 7.3200 5 160 160 4.1 106 - 6 8.3700 11 407 182 3.8 109 21.9 8 9.4000 9 360 153 4.5 103 21 7 10.3800 14 532 156 3.3 103 29.8 8 amount of borate removed was calculated from pressure to the abdomen or to change the position the concentration of pooled aliquots of drainage of the infant to eliminate the last 20 or 30 ml. of and from the total volume of fluid introduced. Al- the peritoneal fluid. The whole procedure was then though the amount of borate removed was not repeated and continued for 36 to 48 hours. great quantitatively, the concomitant improvement in renal function and acidosis and the remarkable Supportive Therapy improvement in the clinical status were evident. Moderate to severe dehydration occurred in most In spite of continuous intravenous infusion during of the patients, and intravenous fluid replacement dialysis, hypernatremia was noted in all cases. is necessary. A knowledge of the serum electrolytes Fortunately this was only a transient abnormality. of the patients serves as a guide to fluid replace- The only complication we experienced was a ment therapy. In all of our cases, hypernatremia gaping of the abdominal wound in one patient who with marked acidosis was treated by a mixture of recovered completely. 5% dextrose in water, 5% dextrose in saline and M/6 sodium lactate. The addition of potassium Procedure and Technique was necessary during the diureses. Salt-poor human albumin was added to the intravenous fluid daily. The procedure and technique employed were patterned and modffied after Segar.6 Strict aseptic The extensive skin lesions were susceptible to technique was practised during the entire pro- secondary infection, and tetracycline was ad- cedure. After injection of local anesthesic (1 % pro- ministered parenteraily for a week. Phenobarbital caine), a small skin incision was made in the left was used as sedative and anticonvulsant. No treat- lower quadrant of the abdomen halfway between ment other than exposure to air was used for the the umbilicus and the superior iliac spine, and the skin lesions. peritoneum was exposed. The peritoneum was then The authors are indebted to Mr. Vic Laxdal, former picked up by a pair of forceps and a tiny nick biochemist of the Grey Nuns' Hospital, for performing made in it though which a multihole plastic dia- the deluge of chemical analyses that were required in these studies. lysis catheter was inserted and directed laterally Acknowledgments are extended to the pediatric nursing into the left pelvic gutter. The dialysis catheters service and the medical records department of the Grey were designed for adults, and it was necessary to Nuns' Hospital for their on-operation. cut off 2 in. from each catheter and to round the We are also grateful to the Department of Pathology under the directorship of the late Dr. John Whittick for end with a flame. When the catheter was inserted, the postmortem studies on the infants who succumbed. a purse-string suture was placed through both the peritoneum and the skin, and the wound was REFERENCES 1. McNALLY, W. D. AND RUST, C. A.: J. A. M. A., 90: 382, finally sealed with collodion. The catheter was then 1928. connected to the short, sterile connecting tube, 2. BARNUM, C. 0.: Ibid., 128: 273. 1945 (abstract). 3. YOUNG, E. G., SMITH, R. P. AND MACINTOSH, 0. C.: which in turn was attached to the dialysing solu- Canad. Med. Ass. J., 61: 447, 1949. tion. A peritoneal dialysis solution (Inperinal, 4. BOGOS, T. R., JR. AND ANRODE, H. G.: Pediatrics, 16: 109, 1955. Abbott) was run into the peritoneal cavity over a 5. CONNELLY, J. P., CRAWF'ORD, J. D. AND SOLOWAY, A. H.: New Eng. .1. Med., 259: 1123. 1958. period of 30 minutes. The amount of fluid infused 6. SEGAR, W. E.: Ibid., 262: 798, 1960. varied, depending upon the degree of respiratory 7. GOLDBLOOM, R. B. AND GOLDBLOOM, A.: .f. Pediat., 43: 631, 1953. distress due to 'abdominal distension and the 8. PFEIFFER, C. C., HALLMAN, L. F. AND GERSH, I.: J. A. M. A., 128: 266, 1945. amount of leakage. Then the upper pinch-clamp 9. McNALLY, W. D. AND RUKSTINAT, G.: Med. Rec. N.Y., 160: was closed and the solution was left in the pen- 284, 1947. 10. BROOKE, C. AND Boocs, T.: A.M.A. J. D.s. Child., 82: toneal cavity for 45 minutes, after which time the 465, 1951. 11. LOCKSLEY H. B. AND SWEET, W. H.: Proc. Soc. Exp. Biol. lower pinch-clamp was opened and the solution Med., 86: 56, 1954. 12. MILLER, N. L. AND FINBERO, L.: New Bag. J. Med., 263: was allowed to drain from the abdomen into a 1347, 1960. container on the floor for a period of about 20 13. FINBERG, L., KILEY, J. AND LUTTRELL, C. N.: J. A. M. A., 184: 187, 1963. minutes. It was often necessary to apply a little 14. ETTELDORP, J. N. et al.: .1. Pediat., 58: 226, 1961.