Sodium Bicarbonate Therapy for Salicylate Poisoning

Sodium bicarbonate therapy for Salicylic acid salicylate poisoning

EUGENE E. GODFREY, n.o. Allentown, Pennsylvania

Aspirin is the most common and cidental deaths in young children than any dangerous poison to children today. other drug. The normal dose of salicylate for a child is A review of the pharmacologic aspects from 1 to 11/2 grains per pound of body weight, of salicylate poisoning provides divided into 6 equal doses, in 24 hours. This is background for the presentation of a usually the top dosage recommended in treat- method of management utilizing ment of rheumatic fever. In infants, in whom sodium bicarbonate. Essential rheumatic fever is uncommon, this amount features of the treatment are the could produce potentially lethal levels in the blood within 24 hours. To avoid iatrogenic early emptying of the stomach and intoxication with salicylic acid or its substi- beginning intravenous administration tutes, the following doses may be given every of fluids and sodium bicarbonate 4 hours: 1/2 grain to an infant from 6 months even before blood studies are to 1 year of age; 1 grain to a year-old child; 1 completed. The use of sodium grain plus an additional grain for each year bicarbonate is based on its ability of age for children to 5 years; 10 grains for children from 5 to 12 years old, and 15 grains to alkalinize the urine and for children past 12. This should not be con- increase the excretion rate of tinued for longer than 24 to 36 hours, unless salicylate ten-fold. Experience the physician reorders it. Unless it is abso- with 16 children with salicylate lutely necessary, salicylic acid or its substi- poisoning, 2 from methyl salicylate tutes should not be given to an infant less than and 14 from aspirin, is reviewed. 3 months old and preferably not to children less than 6 months old. In those with salicylate poisoning from This paper will discuss the role of sodium plain aspirin, the treatment bicarbonate in the treatment of intoxication reduced the blood salicylate below with two salicylate preparations in children. toxic levels in 4 to 6 hours, with These two are methyl salicylate (oil of winter- longer time required in those with green) and salicylic acid (plain aspirin). The methyl salicylate intoxication. former is the more toxic and carries the higher death rate. Death has been reported when the intake of this compound has been as low as 1 teaspoonful. The aspirin substitutes, salicyla- Salicylates are the most common and serious mide and acetaminophen, will not be consid- cause of poisoning treated in children. Other ered in this report, since their toxic action is common offenders are, in the order of their different. importance, barbiturates, iron, antihistamines, In this paper a child has been considered to strychnine, and tranquilizers. The total num- have salicylate intoxication when his serum ber of cases of salicylate poisoning is higher salicylate level was from 30 to 35 mg. per than the total number of cases of barbitu- hundred milliliters or higher or when he had rates, iron, antihistamine, and strychnine ingested more than 1 grain of salicylate per poisoning combined. Salicylates cause more ac- pound of body weight at any one time.

346/64 Signs and symptoms absorption, the salicylate is bound to plasma The clinical signs and symptoms are most im- albumin. This is true when a therapeutic dose portant in the evaluation of salicylate poison- has been taken, and once the binding sites are ing. There is, however, little correlation be- saturated, toxic levels develop.3 The amount tween the severity of the clinical picture and of free salicylate in the serum indicates the the salicylate level. Cases of severe clinical degree of poisoning. toxicity and recovery have been reported in which the level in the serum was 4, 8, or 22 Site of action mg. per hundred milliliters. In other cases, After absorption the salicylate acts within the levels of 50 or 60 mg. were associated with central nervous system as well as peripherally. relatively few symptoms. The one variable in It has been suggested 4 that the peripheral the relation between the salicylate level and effect occurs in skeletal muscle and the central the severity of intoxication is the time that action in the respiratory center of the medul- elapses from ingestion until treatment. The la, located in the midbrain. Salicylate acts as a cardinal signs of salicylate poisoning are stimulus to increased breathing, and the respi- tachypnea and hyperpnea. Hyperpnea is the ratory center becomes increasingly sensitive to more typical, but the two commonly occur the concentration of carbon dioxide and the together. Other signs and symptoms are a his- hydrogen ion content.5 tory of abdominal pain, anorexia, irritability or restlessness, hyperhidrosis, unexplained hy- Respiratory alkalosis perpyrexia (from 103 to 105 F.), vomiting, With hyperpnea, one of the characteristic tinnitus, confusion or hallucinations, and con- signs of salicylism, begins the earliest physio- vulsions progressing to coma. Unexplained logic change, respiratory alkalosis. This is a fever and restlessness are not pathognomonic highly transient phenomenon. The child must of salicylate intoxication, but these signs be seen early if this is to be observed and should arouse suspicion of such poisoning. documented. Respiratory alkalosis is a direct In the late stages, dehydration and cherry-red result of the stimulation of the respiratory lips may be prominent signs. center. It has little direct clinical importance except that it may lead to tetany. Indirectly Pharmacologic aspects however, the effect of respiratory alkalosis is Absorption important, since it predisposes the patient to Salicylate poisoning occurs easily in a child development of metabolic acidosis. The net after ingestion of aspirin, because the drug is result of the respiratory alkalosis is a decrease rapidly absorbed into the blood stream through in arterial and alveolar ventilation, with a the stomach and the upper part of the gastro- resultant decrease in arterial and alveolar car- intestinal tract. Within 30 minutes after inges- bon dioxide pressure and a rise of serum pH. tion, and sometimes earlier, salicylate can be The next stage is metabolic acidosis, which measured in urine and blood samples. The increases ventilatory stimulation and begins peak blood level is reached within approxi- a vicious cycle.4 mately 2 hours after ingestion. 2 Methyl salicylate is absorbed in the same way, but much Metabolic acidosis more slowly and with a later peak.3 After The counter-reaction to the respiratory alkalo-

Journal AOA/vol. 69, December 1969 347/65 Salicylate poisoning

sis is a physiologic adjustment at the renal buffering capacity. Acidosis may be further level, where the hydrogen ion is conserved and increased if renal impairment is present. the urine initially becomes alkaline, with large One point of differentiation between adults amounts of bicarbonate, sodium, and potas- and older children in comparison with infants sium and decreased amounts of chloride pres- and children up to 4 years of age is that adults ent. With a reduction of serum bicarbonate, the usually have persistent respiratory alkalosis blood pH shifts toward normal. With urinary alone, while children, as mentioned previously, loss of appreciable amounts of sodium and have only a transitory phase of respiratory potassium, coupled with extrarenal losses alkalosis, which is rarely seen at the time of through vomiting and sweating, a paradoxical admission to the emergency room or hospital. aciduria may result if depletion is marked. Instead, acidosis is commonly seen. 6 Therefore, Other mechanisms for correction of the alka- it can be inferred that acidosis is present in losis include migration of the hydrogen ion children under the age of 4 who have severe into the extracellular fluid from the cells and symptoms of salicylate poisoning and a carbon bones in exchange for extracellular cations dioxide content of 8 mEq. per liter or less in and the movement of organic acids, principally the plasma. This is true also of infants who lactic acid, from the cells of the serum.° have been subjected to repeated therapeutic The primary cause of the acidosis of sali- overdosage of aspirin and have had symptoms cylate intoxication is the derangement of car- of intoxication for more than 24 hours.° bohydrate metabolism, which will be considered in the section on ketosis. In addition, fat Ketosis is mobilized as a result of the change in carbo- As mentioned previously, the metabolic acido- hydrate metabolism and is converted in the sis seen with salicylism is due largely to de- liver to ketone bodies, which are utilized at rangement of carbohydrate metabolism, pre- this point for body energy. Since ketone bodies sumably of aerobic carbohydrate metabolism. are produced in excess of the capacities of Segar and Holliday have expressed the belief tissue for utilization and of the kidneys for that it interferes with several enzyme systems. excretion, they accumulate as unmeasured Citing evidence that salicylates inhibit the anions in the body fluids. The bicarbonate and oxidative enzymes succinic dehydrogenase and other buffer anions are reduced by the accu- alpha-ketoglutaric dehydrogenase in liver and mulation of organic anions. The faulty aerobic kidney slices, Segar and Holliday suggested carbohydrate metabolism also causes lactic that if this occurs in vivo the amounts of sali- acid and pyruvic acid concentrations to in- cylate in the plasma in poisoning would inhibit crease in the body fluids. Since salicylate is an at least two steps of the tricarboxylic acid acid, its ingestion will increase fixed cation cycle, the conversion of alpha-ketoglutarate excretion. It will also displace some bicar- to succinate and that of succinate to fumarate. bonate in the plasma and increase acidosis. As a result pyruvate would accumulate The metabolic acidosis of salicylate intoxica- or be converted to lactate, and pyruvate tion is, therefore, the result of the increased and lactate would be increased in the tissues. production of various organic acids in an or- If carbohydrate metabolism is seriously im- ganism the defenses of which against acidosis paired, catabolism of fat and protein must be are impaired by a pre-existing depletion of its accelerated, so that the energy needed by the

348/66 body can be obtained from these two sources. again to reduce body temperature to normal When the fat and protein are broken down, depends on its action on the central nervous their by-products add to the acidosis. In addi- system, which can be prevented by hypotha- tion, mere ingestion of salicylates may in- lamic lesions.4 Segar and Holliday have ex- crease the metabolic rate up to 100 per cent pressed the belief that the increase in energy in oxygen consumption, carbon dioxide pro- production is independent of control of either duction, and heat production. ? When all these the central or peripheral nervous system and changes are added together, acidosis is severe. probably occurs in skeletal muscle. Ketosis may be aggravated by starvation and the depletion of hepatic and muscle gly- Dehydration cogen and may exist as a result of these before Dehydration with salicylate poisoning depends salicylates are ingested. Then if salicylates on many factors. As mentioned previously, hy- are ingested, ketosis is increased in severity. perventilation, hyperpyrexia, sweating, vomiting, and diarrhea increase loss of water and Hyperpyrexia electrolytes. Hyperpyrexia accelerates dehy- Salicylates are known to alter the temperature dration, and dehydration potentiates hyper- control center in the medulla. Even though pyrexia. It is known that, once body water aspirin is an antipyretic agent, when the rate stores are depleted, salicylate no longer can of heat production exceeds the capacity of the induce effective sweating, and the drug ceases heat-losing mechanism, hyperpyrexia results. to work. Some researchers 4 have estimated the This can easily occur since salicylate greatly water loss in this condition to be from 80 to increases the metabolic rate of the body. A 100 120 ml. per kilogram of body weight. per cent increase in oxygen utilization and carbon dioxide production has been reported.7•8 Hyperglycemia and hypoglycemia This metabolic • increase becomes a problem Usually an elevation of blood sugar accom- because the regulation of body heat requires panies salicylate intoxication, presumably as a delicate balance between heat production a result of the derangement of carbohydrate and heat loss. The central nervous system, metabolism. Salicylates produce hyperglycemia especially the thermal center, plays an essen- by promoting rapid absorption of carbohy- tial part in regulating the peripheral mecha- drate from the small intestine and increasing nisms concerned with conservation or loss of the rate of depletion of glycogen in the liver.4 body heat. With fever the balance between In addition, adrenocortical steroids are in- heat production and heat loss persists, except creased, and in keeping with this, blood sugar that the thermostat is set at a higher level. is increased and ascorbic acid depleted.4 Salicylate acts to reset the thermostat at a Hypoglycemia is usually a late manifesta- normal temperature. 4 Still another reason for tion of salicylism and occurs after the utiliza- this symptom is that salicylate acts to reduce tion of liver glycogen and the effect of the body temperature by increasing the loss of adrenal steroids have ceased. However, this water, in sweating and increased insensible is uncommon with salicylate intoxication. expenditure of water. This water loss then contributes to dehydration and in turn causes Excretion and action of sodium bicarbonate a temperature rise. The ability of salicylate From 70 to 80 per cent of salicylate is excreted

Journal AOA/vol. 69, December 1969 349/67 Salicylate poisoning

via the kidneys, by filtration and tubular tion is iatrogenic. Even here, however, there excretion. From 20 to 25 per cent is eliminated will be a history of repeated giving of aspirin. from the body by oxidation. Within 24 hours, The symptoms of irritability and unexplained 50 per cent of a given dose is excreted, but fever arouse suspicion as to the nature of the traces of the original dose are detectable up problem. If it is impossible to make the diag- to 48 hours afterward. The percentage ex- nosis from the history, laboratory tests should creted by the kidneys is independent of the be done. dose or urine volume. However, the solute load at first increases the urine output and Laboratory procedures augments the process of dehydration. Salicy- A rapid method of determining whether sali- late is found in the urine as free salicylate, cylate poisoning is the problem is to test the salicylic acid, gentisic acid, and conjugates of urine, first boiling it and then adding 10 per glucuronic and salicylic acid.3 cent ferric chloride. This gives a violet or It has been shown that salicylate which is purple color if salicylate is present. Boiling unbound is dependent on urinary pH for secre- removes the diacetic acid, which is a reducing tion. If the urine is changed from acid to alka- substance that may otherwise give a false- line, there is a 10-fold increase in the excretion positive result. It must be remembered, how- of the free salicylate radical.3 This is the basis ever, that the test may be strongly positive in for sodium bicarbonate therapy of salicylate patients with relatively low blood levels of poisoning. salicylate. The test has little quantitative val- Sodium bicarbonate is thought to alkalinize ue, therefore, but is helpful only in telling the the urine by (1) increasing the pH of the physician that his suspicion could be correct. peritubular fluid, which in turn decreases the A second test, the Phenistix test, is positive stimulus for renal tubular production and when salicylate is present in urine or serum. secretion of hydrogen ion, or (2) neutralizing It is useful for screening patients to determine much of the hydrogen ion secreted into the which children should have quantitative chem- tubular urine by forming poorly dissociated ical analysis. Like the first test, it may give carbonic acid molecule. This, in turn, breaks a false-negative result when intoxication has down to form water and carbon dioxide. Back been present for more than 36 hours, but this diffusion of the carbon dioxide into the tubular rarely is a problem in children. cell and its subsequent reaction with hydroxyl The most reliable diagnostic procedure is, ion to form bicarbonate ion (which is extruded naturally, the quantitative determination of into the peritubular fluid along with the sodi- the serum salicylate level. Other laboratory um ion which entered the cell from the tubular procedures done on the serum at the time of urine in exchange for the hydrogen ion) keep the quantitative determination of salicylate the reaction moving in the direction of con- include measurement of pH, sugar, urea ni- tinuing alkalinization of the urine.9 trogen, and electrolytes, including sodium, chloride, potassium, and carbon dioxide. Pro- Diagnosis thrombin time should be determined immedi- The diagnosis usually can be made on the basis ately and later. For completeness, carbon of the childs history. The only time it is not dioxide and oxygen pressure and the level of apparent in the history is when the intoxica- bicarbonate deficiency should be determined.

350/68 TABLE 1. RESULTS OF BLOOD AND URINE TESTS IN The treatment used on these 16 patients SALICYLATE INTOXICATION was that of Whitten and associates." Before Specimen Test Results this treatment was begun, however, the chil- Urine Urinalysis Some albumin, casts, dren were treated in the emergency room red and white blood either by lavage or by administration of cells syrup of ipecac. The latter treatment was Acetone May be present Diacetic acid May be present found to be preferable, but it may be advisable Phenistix Positive to offer water, juice, soda, or milk to the child Ferric Positive first, since some children refuse to drink other chloride Blood Hematocrit Increased liquids after they have tasted the syrup of Red cells Increased ipecac. Liquids may be given until the child Hemoglobin Increased refuses to drink any more, and will speed Prothrombin Normal or reduced time the action of the medicament. After the fluids, Sugar Initially elevated but from 15 to 20 ml. of syrup of ipecac is given. below 300 mg./100 ml. If an emesis does not occur within 15 minutes, later; hypoglycemia may develop the dose should be repeated, even if force is Carbon di- Lowered after initial necessary. Additional liquids may be offered oxide-com- respiratory alkalosis, to the child in the interim, but the child should bining power otherwise lowered to acidotic range not be forced to take them. Emesis is preferred Electrolytes : over lavage if the child is not in a coma or Potassium Low initially convulsions, for two reasons: (1) more nearly pCO, Reduced p0, Normal or elevated complete emptying of the gastric contents is Serum 30 to 35 mg./100 ml. achieved, and (2) the procedure is not as salicylate or more traumatic to the child. If, however, emesis has not occurred in from 40 to 60 minutes, lavage or induction of vomiting with the finger by the gagging technique will be necessary. The syr- Table 1 shows the results usually observed up of ipecac has its own toxic effect if it is in the blood and urine of a child with salicylate allowed to remain too long in the stomach, intoxication. and must, therefore, be removed. Among 16 children there were no difficulties Treatment encountered in producing emesis with syrup of A total of 49 children with possible salicylate ipecac. However, emesis should not be pro- poisoning were seen. Only those (16) with a duced if a child is comatose or in convulsions. serum salicylate level between 30 and 35 mg. Instead, lavage is done. per hundred milliliters or more received so- If a mother calls the physician from home dium bicarbonate therapy. There were 2 with about possible salicylate ingestion, the physi- methyl salicylate poisoning and initial serum cian may advise her over the telephone to give salicylate levels of 127.5 mg. and 130 mg. per the syrup of ipecac, if it is available in the hundred milliliters, and 14 with intoxication home. If it is not available, the mother should due to plain aspirin. The majority had taken be advised to place her finger in the childs 11/4-grain tablets of childrens flavored aspirin. throat to make the child regurgitate and to

Journal AOA/vol. 69, December 1969 351/69 Salicylate poisoning

transport the child immediately to the hospi- sirable also to repeat the electrolyte measure- tals emergency room. ment. Respiratory and cardiac rates are deter- After the child has vomited, the laboratory mined by the nurse or a monitor every hour tests enumerated in the section on laboratory until treatment is discontinued, usually from procedures are done. Then, immediate sedation 6 to 8 hours. with chloral hydrate or phenobarbital is advis- In children under 4 years of age, sodium bi- able, for two reasons: (1) to overcome the carbonate therapy may be given even though initial irritability phase of salicylate poison- the blood pH is not known. For children over ing, and (2) to reduce the childs resistance the age of 4 years the blood pH should be when fluids are started and a Foley catheter determined before therapy is begun. If shock is inserted. After sedation, the child is re- is present, blood, plasma, or albumin, from 10 moved to the pediatric ward. Immediately on to 15 ml. per kilogram of body weight, should arrival on the floor the Foley catheter is in- be given immediately. Shock was not encoun- serted and intravenous administration of 1,000 tered in any of the 16 patients treated. ml. of 5 per cent glucose and quarter-strength Another drug which is available to combat saline solution, to which have been added 30 acidosis is tromethamine (THAM®) . This has mEq. of sodium bicarbonate, 15 mEq. of potas- been reported to be highly effective, but it may sium chloride, 500 mg. of ascorbic acid, and cause respiratory depression. In medical man- 20 mg. of vitamin K 1, is begun at a rate of agement of salicylate poisoning it may be suit- from 100 to 120 macrodrops per minute. Fif- able for children whose sodium intake must teen minutes after fluids are started, the uri- be restricted. It should be administered only nary pH is checked. If it is acid, 15 mEq. of when the proper equipment and assistants are sodium bicarbonate is given directly by the available to provide artificial respiration. In push technique. After this is given, the urine the present series this preparation was not is checked every 30 minutes. If the urinary pH used. is below 7.5 another 15 mEq. of sodium bicarbonate is given. This dose is repeated every 30 Case reports minutes until the ideal urinary pH, from 7.5 To illustrate the effectiveness of the therapy, to 8, is achieved. After this pH is established, 3 typical cases will be reviewed. The first 2, determinations are continued, and if the pH involving brother and sister, were cases of falls below 7.5, sodium bicarbonate is given methyl salicylate poisoning, while the third again. In the present study, if the pH started was a case of ingestion of salicylic acid. to fall below 7.5, it was necessary to give only 7.5 mEq. of sodium bicarbonate to raise the Case 1 pH back to the ideal range. If the pH ever ap- A 21/2-year-old boy weighing 34 pounds proaches 8, it is usually after this last ad- was seen in the emergency room approxi- ministration of sodium bicarbonate. Otherwise mately 4 hours after ingestion of methyl sali- it remains about 7.5. Determinations of pH cylate. Stomach lavage and blood studies were and of salicylate and carbon dioxide content of done. The blood showed 137 mg. of sodium, 3.8 the blood are repeated every 4 hours until the mg. of potassium, and 105.6 mg. of chloride per salicylate level falls at least to 30 mg. per hundred milliliters, 18.2 mEq. of carbon diox- hundred milliliters. At this time, it may be de- ide, and pH of 7.42. Eight hours later there

352/70 Blood salicylate was finished and another liter started. To this (mg./100 ml.) liter the same amounts of ascorbic acid and 130-139 vitamin K 1 were added. Amounts of sodium Case I 120-129 bicarbonate and potassium chloride were Case 2 110-119 Case 3 •—• —• doubled. This child received a total of 83 mEq. 100-109 of sodium bicarbonate in 22 hours, as shown 90-99 in Figure 2. There were no complications ex- 80-89 cept facial edema, particularly periorbital, 70-79 which subsided within 24 hours after fluids 60-69 were discontinued. 50-59 40-49 Case 2 30-39 A 4-year-old girl weighing 36 pounds showed 20-29 the same symptoms as her brother, but lab- 10-19 oratory tests gave different results. Her blood 0-9 showed 138 mg. of sodium, 4.2 mg. of potas-

Hour of blood 0 4 6 8 10 14 16 20 22 sium, and 102.3 mg. of chloride per hundred sampling milliliters. There was 21.3 mEq. of carbon Fig. 1 dioxide and the pH was 7.38. The initial blood salicylate level was 130 mg. Eight hours later there was 16.6 mEq. of carbon dioxide, and 16 was 18 mEq. of carbon dioxide, and 16 hours hours later there were 143 mg. of sodium, 3.8 later there were 145 mg. of sodium, 3.8 mg. of mg. of carbon dioxide, and 21.8 mEq. of carbon potassium, and 21.8 mEq. of carbon dioxide. dioxide. At the 22d hour, the salicylate level When he was admitted to the emergency room, was 32 mg. per hundred milliliters. The salicy- his blood salicylate level was 127.5 mg. per late levels during treatment are shown in Ta- hundred milliliters. Twenty-two hours after ble 1. From the time she was first seen in the treatment his salicylate level was down to 34 emergency room until 22 hours later, when mg. Table 1 and Figure 1 show blood salicylate treatment was discontinued, the therapy fol- levels at different times during treatment. At lowed was the same as in Case 1. No compli- admission the urinary pH was less than 7, and cations occurred. 5 hours after admission it was between 7.5 and 8, where it remained until therapy was discon- Case 3 tinued. During the 22 hours, 2,000 ml. of fluid A 3-year-old girl weighing 30 pounds had in- was administered. To the first liter, 15 mEq. gested childrens flavored aspirin 1 hour prior of sodium bicarbonate was added, along with to being seen in the emergency room. On ad- 500 mg. of ascorbic acid, 20 mg. of vitamin K1, mission to the emergency room she was given and 15 mEq. of potassium chloride. milk and water, followed by syrup of ipecac. In addition, 15 mEq. of sodium bicarbonate During the examination it was noted that she was given at the 3d hour, 8 mEq. at the 6th had rosy red cheeks and became lethargic. hour, and 15 mEq. at the 10th hour. By the The salicylate level in her blood was 86 mg. per 12th hour the first liter of intravenous solution hundred milliliters, and the serum pH was

Journal AOA/vol. 69, December 1969 353/71 Salicylate poisoning

7.458. The urine was strongly positive for sali- Dosage cylate, and its pH was 5. On arrival in the ward, intravenous administration of fluids 25-30 mEq. containing 30 mEq. of sodium bicarbonate, 20-24 mEq. 15 mEq. of sodium chloride, 500 mg. of ascor- 15-19 mEq. bic acid, and 20 mg. of vitamin IC, was begun. 10-14 mEq. Fluids were discontinued after 6 hours, dur- 5-9 mEq. ing which 1,000 milliliters was given. Also, Hour On I 2 3 4 6 10 12 administered admission 15 mEq. of sodium bicarbonate was given by push method 1 hour after fluids were begun Case 1 Case 2 Case and repeated after a half hour. After another Fig. 2 half hour 7.5 mEq. was given, and was repeated in another half hour by the push technique. At the 4th hour another 7.5 mEq. of TABLE 2. SALICYLATE IN BLOOD (MG./100 ML.) sodium bicarbonate was given directly into DURING SODIUM BICARBONATE THERAPY the tubing (Figs. 1 and 2). Table 2 shows the Hours of blood salicylate levels at different hours dur- treatment Case 1 Case 2 Case 3 ing the treatment. The serum pH, at first Admission 127.50 130.0 86 7.458, rose to 7.53 in 4 hours and fell to 7.40 in 4 92.50 92.5 28 6 93.25 104.5 14 hours and to 7.38 in 24 hours. A total of 8 18 82.5 mEq. of sodium bicarbonate was given 10 75.00 90.0 within the first 4 hours of treatment. During 16 60.00 55.0 <5 20 50.00 52.0 this time the serum was only slightly alkaline, 22 34.00 32.0 while the urinary pH ranged between 7.5 and 8. The prothrombin time, determined during treatment and prior to discharge, remained normal. A urine culture after the Foley Hypokalemia is another hazard. To prevent catheter was withdrawn showed no growth. this, all patients treated with sodium bicar- (This was true also for the other patients bonate received potassium chloride, and no treated with an in-dwelling Foley catheter.) problem of hypokalemia was encountered. During treatment no complications were en- Hypernatremia may be present at the time countered, but the lips became cherry red of admission, as a result of vomiting, hyper- about 3 hours after treatment began. ventilation, fever, and dehydration. If sodium is administered without potassium chloride, Complications the sodium ion will enter the intracellular There are some hazards in bicarbonate treat- fluid and potassium will leave. Hypernatremia ment of acute salicylate intoxication. The most was not encountered or iatrogenically induced, evident is that alkalosis may injure the pa- because potassium chloride was added to the tient. Alkalosis was not serious in the present solution given. series. With proper monitoring of the serum pH and carbon dioxide-combining power, this Comment should not be a serious problem. National figures for accidental poisoning in

354/72 childhood show that aspirin is the most com- methyl salicylate and in 14 from plain aspirin. mon and dangerous poison to children today. When poisoning was with plain aspirin, the Since children suffering from salicylate poi- concentration of salicylate in the blood was soning need quick and adequate treatment, the reduced below toxic levels in 4 to 6 hours. sodium bicarbonate method introduced by Treatment of intoxication with methyl salicy- Whitten and Associates" has many advan- late took longer. Of the 16 patients treated by tages. It is a safe and effective mode of ther- intravenous administration of fluids and sodi- apy. It requires little equipment and is um bicarbonate, 14 had no complications. One universally available, but it does require patient had periorbital edema, which subsided an efficient laboratory for adequate mon- on its own within 12 hours after treatment itoring of the patient with appropriate was discontinued. blood studies. Sodium bicarbonate acts on the urine by making it alkaline, and when it Appreciation is expressed to Drs. James Powell and Kenneth J. Mahoney for referral of cases of salicylate is used in treatment of salicylate intoxication, intoxication. it increases the excretion rate of salicylate 10 times. In differential diagnosis, salicylate intoxi- 1. Craig, J. 0., Ferguson, I. C., and Syme, J.: Infants, toddlers, cation must be distinguished from diabetic and aspirin. Brit Med J 1:757-61. 26 Mar 66 acidosis, from diabetic coma if the patient is 2. Tschetter, P. N.: Salicylism. Amer J Dis Child 106:334-46, Sep 63 comatose, and from pneumonia. These condi- 3. Goodman, L. S., and Gilman, A., Eds.: The pharmacological tions are easily ruled out by urinalysis and basis of therapeutics. A textbook of pharmacology, toxicology, and therapeutics for physicians and medical students. Ed. 2. The Mac- chest x-ray study. millan Company, New York, 1955 4. Seger, W. E., and Holliday, M. A.: Physiologic abnormalities of salicylate intoxication. New Eng J Med 259:1191-8, 18 Dec 58 Summary 5. Winters, R. W.: Salicylate intoxication in infants and children. The pharmacologic aspects of salicylate in- Pediat Clin N Amer 6:281-99, Feb 59 6. Done, A. IC.: Salicylate poisoning. JAMA 192:770-2, 31 May 65 toxication are discussed in relation to absorp- 7. Tenney, S. M., and Miller, R. M.: Respiratory and circulatory tion, site of action, respiratory alkalosis, and actions of salicylate. Amer J Med 19:498-508, Oct 55 8. Miller, R. H., and Tenney, S. M.: Action of sodium salicylate metabolic acidosis with associated ketosis, hy- on tissue gas tensions. Proc Soc Exp Biol Med 92:791-3, Aug- perpyrexia, dehydration, hyperglycemia, and Sep 56 9. SummItt, R. L., and Etteldorf, J. N.: Salicylate intoxication hypoglycemia. in children. Experience with peritoneal dialysis and alkalinizatlon The importance of early emptying of the of the urine. J Pediat 64:803-14, Jun 64 10. Whitten, C. F., Kesaree, N. M., and Goodwin, J. F.: Managing stomach, by either emesis or lavage and of be- salicylate poisoning In children. An evaluation of sodium bicar- ginning intravenous administration of fluids bonate therapy. Amer J Dis Child 101:178-94, Feb 61 and sodium bicarbonate, along with electrolytes, even before blood studies are completed This paper was written during the authors residency in the De- partment of Pediatrics, at the Hospitals, Philadelphia College of is pointed out on the basis of studies of 16 Osteopathic Medicine, of which Dr. William S. Spaeth is chairman. children with salicylate poisoning, in 2 from Dr. Godfrey, 1540 Walnut Street, Allentown, Pennsylvania 18102.

Journal AOA/vol. 69, December 1969 355/73