Comparative Efficacy of Injectable Calcium and Magnesium Salts in the Therapy of Hydrofluoric Acid Burns

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1 CLINICAL TOXICOLOGY, 18(9), pp (1981) Comparative Efficacy of Injectable Calcium and Magnesium Salts in the Therapy of Hydrofluoric Acid Burns JOHN C. HARRIS, MD, and BARRY H. RUMACK,* MD University of Colorado Health Sciences Center; Rocky Mountain Poison Center Denver General Hospital Denver, Colorado DENNIS J. BREGMAN, MS Statistical Services and Evaluation Branch Viral Disease Division Center for Disease Control Atlanta, Georgia ABSTRACT Hydrofluoric acid (HF) causes severe skin burns which often progress in severity despite physiologic neutralization. The currently accepted therapy is the subcutaneous injection of calcium (Ca) gluconate to precipitate the residual free fluoride ion. Magnesium *To whom requests for reprints should be addressed at Rocky Mountain Poison Center, West Eight Avenue & Cherokee, Denver, Colorado Copyright by Marcel Dekker. Inc. 1027

2 102 8 HARRIS ET AL. (Mg) also forms an insoluble fluoride salt and is less tissue irritating than Ca. This study compared the effects of subcutaneous injection of saline, Ca gluconate, Mg acetate (MgAc), and Mg sulfate (MgSOI) on lesions resulting from HF burns in rats. Burns treated with either Mg compound healed 3.7 i 1.7 days faster (p < 0.05), developed less severe lesions (p < 0.01) and exhibited 16 i 12.4% less areal growth of the lesion (p < 0.05) than the burns left untreated or treated with saline. There was no difference in the incidence of infection between the study groups. The effects of burns treated with calcium were statistically similar to the control groups. This study suggests that Mg may be more effective than Ca in minimizing the duration, depth, and progression of dermal HF burns. INTRODUCTION Hydrofluoric acid (HF) is one of the strongest inorganic acids known and is a widely used chemical in many industrial settings including the production of fluorides, plastics, germicides, and insecticides. HF is also used in the ceramic, casting, and etching industry, and as a catalyst in the petroleum industry [l]. As a result of the widespread use of this acid, there are numerous cases of occupational injury from accidental dermal exposure each year [1, 21. Dermal burns from HF differ from burns caused by other acids (such as hydrochloric, sulfuric, and nitric) in that there appear to be two distinct phases of tissue damage. The immediate damage, caused by the high tissue hydrogen ion concentration, is identical to that of other acid burns. However, HF burns, unlike other acid burns, proceed to a second phase of tissue damage which is more severe than the initial phase and may result in continued necrosis over a period of days despite adequate surface decontamination. The pathophysiology of this second phase is poorly understood but is generally thought to be due to the presence of the free fluoride ion (F-) in the tissue [3]. Since calcium forms an insoluble fluoride salt, the currently accepted therapy for this second phase of HF burns has been directed at chemical inactivation of the fluoride ion by subcutaneous infiltration of calcium gluconate [2, Magnesium is also known to form an insoluble salt with fluoride. Because calcium salts are known to be more tissue toxic than magnesium salts, we compared the efficacy of subcutaneous infiltration of calcium gluconate ( CaG), magnesium acetate (MgAc), and magnesium sulfate (MgSOI) in the therapy of HF burns. This paper reports the results of this evaluation performed in rats. METHODS Sprague-Dawley male rats weighing g were anesthetized with methoxyflurane inhalation anesthesia. Hair from the dorsal sur-

HYDROFLUORIC ACID BURNS 1029 face of all four extremities was then shaved with surgical clippers. Twenty-five microliters of HF was then applied by pipette to the shaved skin.

3 HYDROFLUORIC ACID BURNS 1029 face of all four extremities was then shaved with surgical clippers. Twenty-five microliters of HF was then applied by pipette to the shaved skin. After a period of 10 min the skin was decontaminated by a tap water wash. This wash was continuous for a period of 5 min. Forty-five minutes after the initial HF application, the limbs were randomly divided into one of five groups. Group I was a control group which received no therapy other than the tap water wash. Group 11, another control group, was treated with a 0.5-cc intradermal and subcutaneous infiltration of physiologic saline. Groups 111-V, the therapeutic groups, were treated with intradermal and subcutaneous infiltration of 0.5 cc of a 10% solution of either CaG, MgAc, or MgS04, respectively. In Groups 11-V, prior to therapeutic infiltration, the skin was washed with an iodine solution followed by alcohol. The lesions were evaluated by using the following parameters at the time of initial therapy and daily thereafter: A. Depth of the lesion 1. Superficial 2. Into dermis B. C. 3. Through dermis (to muscle fascia) 4. Into muscle Size of the lesion in mm2 Presence or absence of infection (grossly purulent with microscopic WBCs). The lesions were judged as healed when all eschar was gone and scar only remained. To evaluate any inherent toxicities of the therapeutic agents, 20 limbs were prepared as above and randomly divided into the saline control or one of the therapeutic groups without prior HF application. RESULTS The maximum depths of the lesions for all five groups are summarized in Table 1. Note that the depths of the lesions for both control groups were virtually identical. Likewise, there was no significant difference in the depths of the lesions for the two Mg treated groups. In view of this, for statistical purposes, groups were combined to form three larger groups: (1) controls (both no treatment and saline injection), (2) calcium gluconate, and (3) magnesium-treated (Mg acetate and Mg sulfate). These data were analyzed using chi-square tests to contrast superficial damage (Grade 1) to more severe damage (Grade 2-4) for these three groups. The results demonstrated that the magnesium-treated burns were significantly less severe (superficial versus deeper burns) than the control groups (p i 0.01). The calcium group could not be statistically differentiated from either the control or magnesium groups.

4 1030 HARRIS ET AL. TABLE 1. Maximum Depth of Lesion Group (superficial) (dermis) (fascia) (muscle) N NO treatment 59% 15% 11% 15% 27 Saline control 57% 17% 13% 13% 30 Ca gluconate 75% 7% 11% 7% 28 Mg acetatea 90% 3% 6% 0 31 Mg sulfatea 90% 0 10% 0 30 athe magnesium-treated burns were significantly less severe (superficial versus deeper burns) than the two control groups (p < 0.01) Table 2 summarizes the relative areal progression of the lesions between an initial assessment at 24 h after the HF burn to the maximum subsequent measurement. The results were categorized into three levels of relative size between the two measurements: less than 1.5, , and greater than two times the initial measurement. Statistical comparison between the magnesium treatment groups versus the control groups revealed that the areal expansion of the lesion in the magnesiumtreated burns was significantly less than would be predicted from the control group (p < 0.05). The calcium-treated burns were not significantly different than the control or magnesium group, however, unlike TABLE 2. Progression of Lesion Area after HF Burna Group < 1.w OX > 2x N No treatment 56% 2 6% 19% 27 Saline control 53% 2 7% 2 0% 30 Ca gluconate 54% 2 9% 18% 28 Mg acetateb 77% 13% 10% 31 Mg sulfateb 70% 30% 0 30 a Progression of lesion was determined by comparing area (mmz) of necrosis at 24 h after burns (X ) with maximum area of necrosis subsequently noted. bareal progression was significantly less in the magnesiumtreated burns than the two control groups (p < 0.01).

5 HYDROFLUORIC ACID BURNS TABLE 3. Duration of Lesion (Days) - Group X S.D. N P No treatment Saline control NS Ca gluconate NS Mg acetate <O. 05 Mg sulfate c0.05 the maximum depth of lesion where calcium fell midway between control and magnesium treatment. For progression of lesion, the calciumtreated burns were essentially identical with the control groups. For both of these measurements, maximum depth of lesion and areal progression of lesion, the magnesium-treated burns were significantly less severe than the control groups. Table 3 summarizes the duration of lesion for each group. Statistical analysis by Duncan's Multiple Range test revealed only the MgAc and MgS04 -treated burns healed significantly faster than controls (p < 0.05). This difference cannot be accounted for on the basis of infection since only two of the Ca-treated lesions and one lesion in each of the remaining four groups became grossly purulent. Finally Table 4 shows the results of intradermal and subcutaneous injection of saline, Ca, and Mg salts in the absence of HF application. Only Ca gluconate injection produced subsequent lesions. TABLE 4. HF Burn) Intradermal and Subcutaneous Infiltration Only (No Number of limbs with Infiltrating agent Number of limbs treated subsequent lesionsa Saline 5 0 Ca gluconate 5 3 Mg acetate 5 0 Mg sulfate 5 0 Lesion is defined as well demarcated area of necrosis greater a than 2.0 mm in diameter.

1032 HARRIS ET AL. DISCUSSION The widespread industrial use of HF has resulted in repeated accidental dermal burns in the occupational setting [ 1, 21.

6 1032 HARRIS ET AL. DISCUSSION The widespread industrial use of HF has resulted in repeated accidental dermal burns in the occupational setting [ 1, 21. Therapeutic approaches to these burns has in the past included the use of magnesium ointment [8], cold hyamine, or Zephiram soaks [9], and, most recently, injection of calcium gluconate into the burned area [4-71. Although previous investigations have supported the efficacy of Ca injection for the treatment of HF burns, the use of Mg salt infiltration has not been previously evaluated. In this study comparing the use of intradermal and subcutaneous injection of Ca and Mg salts, both MgAc and MgS04 were more effective than Ca gluconate in minimizing the depth and progression of HF burns. More surprising is the fact that Ca gluconate infiltration did not (as suggested by previous studies) significantly hasten healing of HF burns. However, HF burns treated with either magnesium salt healed significantly faster than the two control groups. Although the theoretical advantage of both Ca and Mg are identical, perhaps the apparent efficacy of Mg over Ca is a result of the greater inherent tissue toxicity of high Ca concentration. In summary, we have compared the efficacy of magnesium and calcium salts in the therapy of hydrofluoric acid burns in rats. Our results suggest that infiltration of Mg may be more effective than infiltration of Ca in the acute treatment of HF burns. REFERENCES Occupational Diseases-A Guide to Their Recognition, USDHEW, USPHS, CDC (NIOSH Publication No ), Revised June 1977, pp J. V. Klauder, L. Shelanski, and K. Gabriel, Industrial uses of compounds of fluorine and oxalic acid, Arch. Ind. Health, - 12, (1955). J. Simons, Fluorine Chemistry, Vol. 1, Academic, New York, 1950, p R. E. Iverson and D. R. Laub, Hydrofluoric acid burn therapy, Surg. Forum, 21, (1970). R. E. Iverson,D. R. Laub, and M. S. Madison, Hydrofluoric acid burns, Plast. Reconstr. Surg., 48(2), (1971). P. F. Dieffenbacher and J. H. Thompson, Burns from exposure to anhydrous hydrofluoric acid, J. Occup. Med., 4, (1962). A. Paley and J. Seiffer, Treatment of experimencal hydrofluoric acid corrosion, Proc. SOC. Exp. Biol. Med., 46, ( 1941). L. Mayer and J. Guelich, Hydrogen fluoride chalation and burns, Arch. Environ. Health, 7, (1963). J. M. Wetherhold and F:P. Shepherd, Treatment of hydrofluoric acid burns, J. Occup. Med., - 7, (1965).

Standard Operating Procedure (SOP)

Standard Operating Procedure (SOP) INTRODUCTION This SOP applies to HYDROFLUORIC ACID (HF). HYDROFLUORIC ACID is one of the strongest acids. It is extremely destructive to tissue and potentially fatal. HF causes such severe burns because