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Hydrofluoric acid: A review of toxicity
The journal
of Emergency
Medmne,
PrInted in the USA
Vol IO, pp 163-l 66, 1992
Copynght
lk 1992 Pergamon
Press Ltd
HYDROFLUORIC ACID: A REVIEW OF TOXICITY John C. Bertolini, Associate
DIrector, Reprint
Department of Emergency Medicine, Malcolm Emergency Department, Marian Health
Address:
0 Abstract -Hydrofluoric acid is a toxic substance used widely in both industrial and domestic settings. It can cause severe burns, as well as systemic toxicity. Death has been reported from as little as 2.5% body surface area (BSA) burn involving concentrated acid. Topical and parenteral calcium salts have proven effective therapy for both dermal and systemic manifestations. All emergency physicians should be aware of the unique complications and treatment of these injuries. 0 Keywords- hydrofluoric acid; fluoride; burns, chemical; fluorosis, systemic; hypocalcemia INTRODUCTION
Hydrofluoric acid (HF) is the inorganic acid of elemental fluorine. It is widely used in the glass etching, electronics, and chemical industries. Hundreds of tons of the substance are used by oil refineries as a catalyst to produce higher octane fuel (1). When diluted it is an excellent agent for removing rust stains from fabrics, and is a component of many household and commercial rust removers. In 1989, 1032 exposures to hydrofluoric acid were reported to the American Association of Poison Control Centers National Collection System (2). Of these exposures, 86% were in adults and 99% were accidental. Despite its widespread use, many medical practitioners outside industrial medicine know little about the substance and its potential for significant morbidity and mortality. The purpose of this article is to describe the range of toxicity of hydrofluoric acid and review the treatment regimens discussed in the medical literature for various hydrofluoric acid injuries.
MD
Grow USAF MedIcal Center, Andrews AFB, Maryland Center, 801 Fifth Street, Sioux City, IA 51101
PATHOPHYSIOLOGY
Like other organic acids, HF produces dehydration and corrosion of tissues due to free hydrogen ions. However, unlike other acids, the dissociated fluoride ion, F-, produces severe toxicity. The fluoride ion complexes certain bivalent cations, primarily calcium and magnesium, to form insoluble salts. This interferes with calcium metabolism in the underlying soft and bony tissues and results in severe pain and cell destruction. With a severe burn, systemic toxicity may also result, with hypocalcemia and hypomagnesemia. Most acids produce immediate pain on contact due to the chemical burn caused by dissociated H+ ions. However, because of the affinity of the F- ion, HF is a relatively weak acid in dilute solutions, and few free H + ions exist. Because there may be little or no initial pain with exposure to weaker solutions, the burn may go undiscovered for a period of time. This time lag between exposure and decontamination allows time for deeper penetration of the fluoride in the undissociated HF form and a more severe burn (5). The National Institute of Health-Division of Industrial Hygiene has classified hydrofluoric acid burns on the basis of HF concentration in the offending agent (3). Concentrations of greater than 50% always cause immediate pain with readily apparent tissue destruction. Concentrations of 20% to 50% result in the burn becoming apparent within several hours of the exposure. Dilute concentrations of less than 20% may take up to 24 hours to become apparent. The severity of hydrofluoric acid burns is a prod-
Toxicology- one of the most critical and challenging areas confronting the emergency department staff -is coordinated by Kenneth Kulig, MD, of Denver, Colorado. RECEIVED: 14December 1990; FINALSUBMISSIONRECEIVED: 8 July 1991; 0736-4679192 $5.00 + .OO ACCEPTED: 5 August 1991
=
=
164
John C. Bertolini
UCt Of concentration, surface area involved, and the duration of exposure (time until decontamination). Once they become apparent, burns from hydrofluoric acid produce a characteristic excruciating pain, often not capable of being adequately controlled with parenteral narcotics. It has been postulated that conjugation with F- ions results in a depletion of available calcium. This causes local nerve endings to release cellular potassium and discharge frequently (4).
TREATMENT Treatment for hydrofluoric rized in Table 1.
acid exposure is summa-
Primary First Aid Despite the differences described between hydrofluoric and other inorganic acids, the initial care of such burns is the same. This includes 1) complete disrobing of the patient, 2) immediate copious irrigation of the area with tepid water, 3) an attempt to identify the offending agent, and 4) treatment of systemic toxicity when present. It is important not to delay initiation of irrigation in order to search for a neutralizing agent. This is time-consuming and delays the critical step of decontamination. Neutralization also produces an exothermic reaction that can cause thermal injury and is therefore not recommended. Sterile irrigating solution is not necessary. After performing these initial stabilizing measures, there are a variety of methods to precipitate and eliminate the fluoride ion and prevent progressive tissue destruction. The best method to use in each case depends on the severity and location of the burn.
Table 1. Summary of Treatment Exposure
for Hydrofluoric
Acid
1) Decontaminate patient by removing contaminated clothing and flushing exposed areas with large amounts of water. 2) Apply calcium gluconate gel topically. 3) Consider subcutaneous injection of calcium gluconate for symptoms not responsive to topical therapy. Consider intraarterial infusion for severe extremity burns. 4) Anticipate systemic toxicity in exposures involving concentrated acid, or in ingestions. Institute cardiac monitoring. Establish intravenous access. Evaluate calcium, potassium, and other electrolyte levels. Be prepared to treat hypocalcemia with large amounts of intravenous calcium. Consider hemodialysis to treat fluorosis and hyperkalemia.
Dermal Injury Topical therapy. Over the years there has been considerable debate as to the optimal topical treatment of HF burns. Calcium or magnesium gels or pastes, so-called HF burn ointment, have been used since first described by Fredenhagen and Wellman in 1932 (5). Calcium gel can be made by mixing 3.5 g of calcium gluconate with 5 ounces of a water soluble lubricant such as K-Y jelly (1). This results in a gel containing approximately 2.5% calcium gluconate. Calcium gel is not commercially available in the United States. Others have advocated topical treatment with a quaternary ammonium compound such as Zephiran, which is thought to exchange ionized chloride for fluoride ions, resulting in a non-ionized fluoride complex (6). Goodfellow has advocated simple flushing with water and treatment with iced water until the pain subsides (7). However, since this treatment does nothing to arrest the damage being done by the free F- ions, pain relief may be due to cold anesthesia rather than effective treatment. Little controlled research has been done to evaluate the effectiveness of various topical treatments. One such study evaluated the effectiveness of calcium gluconate (2.5%) burn jelly, Zephiran, magnesium ointment, aloe gel, and A&D ointment on experimentally induced HF burns of the hind legs of rats. It finds that calcium gluconate gel is most effective in mitigating the damage caused by concentrated hydrofluoric acid (8). Topical therapy is effective primary treatment after decontamination has been carried out. It is easily administered by the patient or other non-healthcare workers. Some advocate these topical therapies as definitive treatment for minor burns, such as those caused by low concentrations of HF where decontamination is accomplished rapidly. Browne is a strong advocate of topical therapy with calcium gluconate gel (9). He recommends continual massage of the gel into the wound for up to several hours, so long as there is continued pain relief and improvement. Edelman endorses treating such wounds topically for 45 minutes. If there is complete pain relief, then the treatment should be considered adequate (10). A vinyl glove can be used as an occlusive dressing once calcium gel has been applied to hand burns. Parenteral therapy. If pain relief is incomplete or symptoms recur, subcutaneous injections of calcium gluconate are indicated. This modality has been shown to result in dramatic relief of pain and im-
Hydrofluoric Acid Toxicity
provement of lesion appearance (11,12). The injections should be carried out using a 27- or 30-gauge needle. The subcutaneous tissues under the involved skin should be injected from sites on the periphery of the lesion. A dose of 0.5 cc per square centimeter of 10% calcium gluconate is used (13). Although calcium chloride has more milliequivalents per cc of calcium, it is contraindicated for subcutaneous infiltration due to its tissue irritating properties (14). There is a difference of opinion on whether local anesthetic should be used with calcium injections. Pain relief is often immediate from calcium alone. Advocates of withholding anesthetics feel that the return of pain indicates a need for further injectable calcium treatment and prefer not to mask the potential return of symptoms. A study done by Harris and Rumack raised controversy over the agent of choice for subcutaneous infiltration of HF burns (15). An unspecified concentration of HF was used to produce burns in a rat extremity model. They then compared the effects of intradermal and subcutaneous infiltration of calcium gluconate, magnesium sulfate, and magnesium acetate on wound healing. Their results show both magnesium salts to be more effective than calcium gluconate in limiting extension and depth of the wounds. This study has been criticized by Edelman. He points out that although all the salts were used as a 10% solution (weight/volume), because of differences in molecular weights of the compounds the molar concentration of magnesium in the solutions was up to eight times that of calcium (10). No controlled human studies have been performed. The vast majority of clinical experience in treating HF wounds has been with calcium gluconate. It is considered to be the agent of choice at this time (14). Digital and hand burns deserve special mention as they are frequently seen, especially in industrial settings. Because of the lack of subcutaneous space, relatively little solution can be injected without concern for compromise of tissue perfusion. This volume limitation can be a problem in more concentrated HF burns. One half milliliter of 10% calcium gluconate contains only enough elemental calcium to neutralize 0.025 ml of 20% HF (16). Anderson and Anderson advocate a treatment regimen for hand burns emphasizing immediate skin cleansing, topical calcium gel, and subcutaneous injections of calcium gluconate when necessary (1). If pain persisted for more than 30 minutes after using calcium gel, they injected calcium gluconate in the method previously described. A palmar fasciotomy was done on any injected fingertips to avoid potentially dangerous high tissue pressures. Any patient
165
with subungual pain or periungual tissue involvement had the nail of that digit removed. They observe that only the patients who required nail excision need regional anesthesia, all others have dramatic pain relief with calcium gel alone or in combination with tissue injection of calcium gluconate. The issue of nail removal when periungual tissues are involved is a controversial one. Edelman is in agreement with the above approach. He supports removal of the nail for subungual pain or discoloration (10). Pegg also states that severe pain under the nail is an indication for nail removal (20), as does Iverson and colleagues (12). In a recent review, the issue is not specifically addressed except to state that removal of the nail is often indicated when subungual tissue is involved (14). However, Roberts and Merigan report good success in treating dilute (less than 10%) hydrotluoric acid burns to the nail area in a more conservative fashion. In their experience these burns do not result in significant tissue destruction, although they can be quite painful. They use topical therapy, with longacting digital nerve blocks for pain control (17). If injections to the nailbed area are required, they suggest a lateral or volar approach under digital anesthesia without nail removal. They do advise nail removal for burns with more concentrated acid. Digital burns involving highly concentrated hydrofluoric acid are a difficult problem. Large amounts of fluoride ion need to be neutralized, but tissue space limits the volume of solution that can be injected. Koehnlein and colleagues were the first to describe intraarterial infusions of calcium gluconate as treatment for severe hydrofluoric acid burns of the limbs (18). This technique avoids the problems of increased tissue pressure encountered when injecting into the hands and digits, while at the same time delivering large amounts of calcium to affected tissues. There are several reports in the literature describing good results with this technique (18-2 1). The basic technique used by Vance and colleagues (19) consists of the following: 1) Percutaneous cannulation of the radial artery with a long catheter; 2) Insertion of the catheter proximally several centimeters into the radial artery for burns to the thumb, index, or middle fingers. Or alternatively, the catheter is advanced proximally into the brachial artery allowing access to the ulnar circulation for burns involving the ring or small finger; 3) Arteriogram to confirm blood supply to the injured area; 4) Infusion of dilute solution of calcium salts with a pump apparatus over a 4-hour period (10 ml of a 10% solution of calcium glucconate or calcium chloride in 40 to 50
166
ml of 5% dextrose). If pain from the HF burn returns within a 4-hour observation period, the infusion cycle is repeated as necessary until the patient remains symptom free. Minor complications such as local arterial spasm usually respond to infusion of vasodilators or removal of the catheter (19). Advantages of intraarterial therapy include the ability to deliver large doses of calcium in a relatively painless manner and the avoidance of the need for fingernail removal. Disadvantages include the invasive vascular procedure necessary and the need for hospitalization with monitoring of the infusion.
Ocular Injury
Ocular exposure also warrants special mention. The potential for significant injury to this organ is great. Care must be taken not to cause additional iatrogenic damage. McCulley and colleagues report that many of the topical modalities used to treat skin burns effectively cause injury to the eye experimentally. In a rabbit model, irrigation with Zephiran or Hyamine or subconjunctival injections of 10% calcium gluconate each causes injury to normal eyes. Immediate, one-time irrigation with water, isotonic saline, or magnesium chloride is found to be effective and nontoxic. Repeated irrigation causes an increase in corneal ulceration. Irrigation with isotonic calcium chloride also causes an increase in cornea1 ulceration (22). Trevino and colleagues recommend 1% calcium gluconate in saline as an irrigant, followed by instillation of 1% calcium gluconate drops every 2 to 3 hours for several days (23). Browne also recommends use of calcium gluconate drops (9). There have been no controlled studies to support or refute this recommendation. After irrigation, instillation of anesthetic drops to relieve pain and cycloplegics to dilate the pupil may be indicated (24,25). Steroid drops have also been advocated to lessen fibroblast formation in the cornea (23,24). Prompt ophthalmologic consultation is indicated.
Systemic Toxicity
Systemic fluorosis can be a concern with any significant exposure. Systemic toxicity has been reported after ingestion of sodium fluoride, inhalation of HF vapors, and in skin burns. There are numerous case reports in the literature documenting the lethality of such exposure, including one case of homicide reported in the forensic medicine literature (26).
John C. Bertolini
Mayer and Gross reported fatal systemic fluorosis from a 70% HF burn involving 9% to 10% BSA on the lower extremities in a healthy 23-year-old male (27). The patient was immediately undressed, washed in a shower, and transferred to a local emergency department. Several hours later he developed ventricular fibrillation that responded to defibrillation and lidocaine. He was then transferred to a tertiary center, 6 hours after the exposure. The patient experienced several episodes of ventricular tachycardia and developed cardiovascular collapse 11 hours post exposure. A serum calcium determination available at that time was 3.3 mg%. Despite a total of 5 amps of calcium chloride and aggressive resuscitation efforts, the patient expired 17 hours post exposure. Greco and colleagues report three cases of severe fluorosis with hypocalcemia following concentrated hydrofluoric acid burns (28). All of the patients had admission calcium levels of 4.1 mg% or below, one despite administration of subcutaneous and intravenous calcium prior to serum determination. Two patients survived, both after exposure to 70% acid. One received 113.2 mEq of calcium after a 2.5% BSA burn of the face and neck. The other received a total of 266.7 mEq after a 22% BSA injury involving scalp, neck, shoulders, torso, and extremities. The latter is equivalent to 57 amps of 10% calcium gluconate or 19 amps of calcium chloride. Tepperman described a fatal 2.5% BSA burn of the face with anhydrous HF acid in a refinery worker (29). The patient developed ventricular fibrillation approximately 5 hours after injury and died several hours later. Admission serum calcium was 3.5 mg/ dL, just prior to his first dysrhythmia. Despite receiving 280 mEq of calcium over the subsequent few hours, the serum calcium never rose above 3.1. Although this burn involved the face, there was no evidence of airway burn observed during endotracheal intubation. Thus, it was postulated that the systemic toxicity was due solely to dermal absorption of fluoride. There was no clinical evidence of hypocalcemia in the form of tetany. There was, however, mild prolongation of the Q-T interval on ECG. Buckingham describes a 5% BSA burn to the forearm that resulted in bradycardia, QT prolongation, and ventricular fibrillation. Admission serum calcium was noted to be 3 mEq/L. The patient responded transiently to “large” doses of intravenous calcium, but then deteriorated. The decision was made to excise the wound operatively to stop systemic absorption of F- ion, and the patient recovered (30). Tetany was specifically looked for on several occasions and was absent. Chan and colleagues reported on two workers who
167
Hydrofluoric Acid Toxicity
died from burns and inhalation of vapors shortly after being exposed to 70% hydrofluoric acid (31). They were splashed with the liquid when a hose being used to unload a tank truck came loose. The authors commented on the lack of effective therapy for massive HF exposure and the need for protective clothing and self-contained breathing apparatus for workers dealing with concentrated HF. The literature also contains reports of systemic toxicity and death following oral intake of fluoride compounds. Yolken and colleagues describe a pediatric ingestion of a commercial laundry powder (32). Abukurah and colleagues reported the ingestion of an insecticide containing sodium fluoride in a suicide attempt (33). Both patients survived after stormy hospital courses including multiple episodes of ventricular fibrillation and treatment with large doses of parenteral calcium. These cases demonstrate that very small cutaneous burns from concentrated HF can rapidly become fatal. Severe hypocalcemia and systemic fluorosis (when fluoride levels are obtained) are the hallmarks of severe poisoning. In the majority of the cases, clinical evidence of hypocalcemia such as tetany, Chvostek’s sign, and Trousseau’s sign are absent. Therefore, all patients with significant exposures need to be placed on cardiac monitors, have intravenous access established, and have rapid and serial evaluation of calcium and other electrolyte levels. Electrocardiographic changes, such as Q-T prolongation, may provide valuable evidence of hypocalcemia. A Q-T prolongation on the ECG due to hypocalcemia is well recognized. It is of interest that major texts do not mention ventricular fibrillation as a manifestation of hypocalcemia (34,35). In Rosen’s text, it is stated that myocardial tetany occurs prior to the development of complex dysrhythmias (34). In the majority of cases discussed above, ventricular fibrillation was seen.
The tendency of severely poisoned patients to die in ventricular fibrillation may be due to the direct toxicity of the fluoride ion on the myocardium (27,36). The role of fluoride-induced hyperkalemia in fatal hydrofluoric acid exposures has also been questioned (36). In a canine model, it has been shown that fluoride poisoning produces hyperkalemia and that lethal ventricular dysrythmias are temporally more closely related to this event than to the development of hypocalcemia (37). When treating systemic toxicity from hydrofluoric acid exposure, the clinician should be prepared to administer intravenous calcium early and in large doses. The induction of metabolic alkalosis with sodium bicarbonate will enhance renal excretion of the fluoride ions (38). Fluoride can also be removed by hemodialysis or cation exchange resins (37,39). Hemodialysis will treat the hyperkalemia that some feel is an important factor in the development of dysrhythmias. Removal of fluoride may be the most important intervention in the treatment of the systemically ill patient (36,37).
SUMMARY Hydrofluoric acid has the potential to cause significant injury due to the unique toxicity of the dissociated fluoride ion. Calcium salts have proven to be effective therapy in treating such injuries. New methods of delivery such as intraarterial infusion have improved the prognosis of severe extremity burns. All emergency physicians need to be aware of the potentially life threatening systemic manifestations of significant burns and their treatment.
author thanks Keith Ghezzi, for his thoughtful comments and editorial review.
Acknowledgments-The
MD,
REFERENCES 1. Anderson WJ, Anderson JR. Hydrofluoric acid burns of the hand: mechanism of injury and treatment. J Hand Surg. 1988; 13A:52-7. 2. Litovtiz TL, Schmitz BF, Bailey KM. 1989 Annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med. 1990;8:394-442. 3. Division of Industrial Hygiene, National Institutes of Health. Hydrofluoric acid burns. Ind Med. 1943;12:634. 4. Klauder JV, Shelanski L, Gabriel K. Industrial uses of compounds of fluoride and oxalic acid. Arch Ind Health. 1955; (12):412-19. 5. Fredenhagen K, Wellman M. Atzwirkungen des Fluorwasserstoffs und Gegenmittel. Angew Chem. 1932;45:537. 6. Reinhart CF, Hume WG, Lynch AL, Wetherhold JM. Hydro-
fluoric acid burn treatment. J Am lnd Hygiene. 1966;27:16671. 7. Goodfellow RC. Hydrofluoric acid burns [letter]. Br Med J(Clin Res). 1985;23;290:937. 8. Bracken WM, Cuppage F, McLaury RL, Kirwin C, Klaassen CD. Comparative effectiveness of topical treatment for hydrofluoric acid burns. J Occup Med. 1985;27:733-9. 9. Browne TD. The treatment of hydrofluoric acid burns. J Sot Occup Med. 1974;24:80-9. 10. Edelman P. Hydrofluoric acid burns. State Art Rev Occup Med. 1986;1(1):89-103. 11. Blunt CF. Treatment of hydrofluoric acid skin burns with injection of calcium glucconate. Ind Med Surg. 1964;(33):869-
John C. Bertolini 12. Iverson RE, Laub DR, Madison MS. Hydrofluoric acid burns. Plast Reconstr Surg. 1971;48(2):107-12. 13. Dibbell DC, Iverson RE, Jones W, Laub DR, Madison MS. Hydrofluoric acid burns of the hand. J Bone Joint Surg. 1970; 52A:931-6. 14. Caravati EM. Acute hydrofluoric acid exposure. Am J Emerg Med. 1988;6:143-50. 15. Harris JC, Rumack BH. Comparative efficacy of injectable - calcium and magnesium salts in the therapy of hydrofluoric acid burns. Clin Toxicol. 1981:18:1027-32. 16. Carney SA, Hall M, Lawrence JC, et al. Rationale for the treatment of hydrofluoric acid burns. Br J Ind Med. 1974;31: 317-21. 17. Roberts JR, Merigan KS [letter]. Am J Emerg Med. 7(1):1256. 18. Koehnlein HE, Seitz HD, Achinger R. Abstracts of 5th International Congress on Burn Injuries, Stockholm, Sweden, 1978. 19. Vance MV, Curry SC, Kunkel DB, Ryan PJ, Ruggeri SB. Digital hydrofluoric acid burns: treatment with intraarterial calcium infusion. Ann Emer Med. 1986;15:890-6. 20. Pegg SP, Siu S, Gillet Ci. Intraarterial infusions in the treatment of hydroflporic acid burns. Burns Inc Therm Inj. 1985; Aug 11:440-6. 21. Edinburg M, Swift R. Hydrofluoric acid burns of the hands: a case report and suggested management. Aust N Z J Surg. 1989;59(1):88-91. 22. McCulley JP, Whiting DW, Petitt MC, Lauber SE. Hydrofluoric acid burns of the eye. J Occup Med. 1983;25:447-50. 23. Trevino MA, Herrmann GH, Sprout WL. Treatment of severe hydrofluoric acid exposures. J Occup Med. 1983;25:861-3. 24. Vaughn D, Asbury T. General ophthalmology. Los Altos, Califorma: Lange; 1983:39. 25. Tintinalli JE. Hydrofluoric acid burns. JACEP. 1978;7:24-6. 26. Chela A, Reig R, Sanz P, Huguet E, Corbella J. Death due to
hydrofluoric acid. Am J Forensic Med Pathol. 1989;10(1):478. 27. Mayer TG, Gross PL. Fatal systemic fluorosis due to hydrofluoric acid burns. Ann Emer Med. 1985;14:149-53. 28. Greco RJ, Hartford CE, Haith LR, Patton ML. Hydrofluoric acid induced hypocalcemia. J Trauma. 1988;28:1593-6. 29. Tepperman PB. Fatality due to acute systemic fluoride poisoning following a hydrofluoric acid skin burn. J Occup Med. 1980;22:691-2. 30. Buckingham FM. Surgery: a radical approach to severe hydrofluoric acid burns. J Occup Med. 1988;30:873-4. 31. Chan KM, Svqancarek WP, Creer M. Fatality due to acute hydrofluoric acid exposure. J Toxic01 Clin Toxicol. 1987;25: 333-9. 32. Yolken R, Konecny P, McCarthy P. Acute fluoride poisoning. Pediatrics. 1976;58:90-3. 33. Abukurah A, Moser AM, Baird CL, Randall RE, Setter JG, Blanke RV. Acute sodium fluoride poisoning. JAMA 1972; 222:816-7. 34. Rosen P, ed. Emergency medicine: current concepts and clinical practice. 2nd ed. St. Louis: CV Mosby; 1988:2002. 35. Potter J. Disorders of bone and mineral metabolism. In: Braunwald E, ed. Harrison’s principles of internal medicine. New York: McGraw Hill; 1987:1882. 36. McIvor ME. Delayed fatal hyperkalemia in a patient with acute fluoride intoxication. Ann Emerg Med. 1987;16:1165-7. 37. McIvor ME, Cummings CE, Mower MM, et al. Sudden cardiac death from acute fluoride intoxication: the role of potassium. Ann Emerg Med. 1987;16:777-81. 38. Reynolds KE, Whitsford GM, Pashley DH. Acute fluoride toxicitv: the influence of acid base status. Toxic01 Appl Pharmacol: 1978;45:415-27. 39. Berman L, Taves D, Mitra S, Newmark K. Inorganic fluoride poisoning: treatment by hemodialysis. N Engl J Med. 1973; 289:922.
of Emergency
Medmne,
PrInted in the USA
Vol IO, pp 163-l 66, 1992
Copynght
lk 1992 Pergamon
Press Ltd
HYDROFLUORIC ACID: A REVIEW OF TOXICITY John C. Bertolini, Associate
DIrector, Reprint
Department of Emergency Medicine, Malcolm Emergency Department, Marian Health
Address:
0 Abstract -Hydrofluoric acid is a toxic substance used widely in both industrial and domestic settings. It can cause severe burns, as well as systemic toxicity. Death has been reported from as little as 2.5% body surface area (BSA) burn involving concentrated acid. Topical and parenteral calcium salts have proven effective therapy for both dermal and systemic manifestations. All emergency physicians should be aware of the unique complications and treatment of these injuries. 0 Keywords- hydrofluoric acid; fluoride; burns, chemical; fluorosis, systemic; hypocalcemia INTRODUCTION
Hydrofluoric acid (HF) is the inorganic acid of elemental fluorine. It is widely used in the glass etching, electronics, and chemical industries. Hundreds of tons of the substance are used by oil refineries as a catalyst to produce higher octane fuel (1). When diluted it is an excellent agent for removing rust stains from fabrics, and is a component of many household and commercial rust removers. In 1989, 1032 exposures to hydrofluoric acid were reported to the American Association of Poison Control Centers National Collection System (2). Of these exposures, 86% were in adults and 99% were accidental. Despite its widespread use, many medical practitioners outside industrial medicine know little about the substance and its potential for significant morbidity and mortality. The purpose of this article is to describe the range of toxicity of hydrofluoric acid and review the treatment regimens discussed in the medical literature for various hydrofluoric acid injuries.
MD
Grow USAF MedIcal Center, Andrews AFB, Maryland Center, 801 Fifth Street, Sioux City, IA 51101
PATHOPHYSIOLOGY
Like other organic acids, HF produces dehydration and corrosion of tissues due to free hydrogen ions. However, unlike other acids, the dissociated fluoride ion, F-, produces severe toxicity. The fluoride ion complexes certain bivalent cations, primarily calcium and magnesium, to form insoluble salts. This interferes with calcium metabolism in the underlying soft and bony tissues and results in severe pain and cell destruction. With a severe burn, systemic toxicity may also result, with hypocalcemia and hypomagnesemia. Most acids produce immediate pain on contact due to the chemical burn caused by dissociated H+ ions. However, because of the affinity of the F- ion, HF is a relatively weak acid in dilute solutions, and few free H + ions exist. Because there may be little or no initial pain with exposure to weaker solutions, the burn may go undiscovered for a period of time. This time lag between exposure and decontamination allows time for deeper penetration of the fluoride in the undissociated HF form and a more severe burn (5). The National Institute of Health-Division of Industrial Hygiene has classified hydrofluoric acid burns on the basis of HF concentration in the offending agent (3). Concentrations of greater than 50% always cause immediate pain with readily apparent tissue destruction. Concentrations of 20% to 50% result in the burn becoming apparent within several hours of the exposure. Dilute concentrations of less than 20% may take up to 24 hours to become apparent. The severity of hydrofluoric acid burns is a prod-
Toxicology- one of the most critical and challenging areas confronting the emergency department staff -is coordinated by Kenneth Kulig, MD, of Denver, Colorado. RECEIVED: 14December 1990; FINALSUBMISSIONRECEIVED: 8 July 1991; 0736-4679192 $5.00 + .OO ACCEPTED: 5 August 1991
=
=
164
John C. Bertolini
UCt Of concentration, surface area involved, and the duration of exposure (time until decontamination). Once they become apparent, burns from hydrofluoric acid produce a characteristic excruciating pain, often not capable of being adequately controlled with parenteral narcotics. It has been postulated that conjugation with F- ions results in a depletion of available calcium. This causes local nerve endings to release cellular potassium and discharge frequently (4).
TREATMENT Treatment for hydrofluoric rized in Table 1.
acid exposure is summa-
Primary First Aid Despite the differences described between hydrofluoric and other inorganic acids, the initial care of such burns is the same. This includes 1) complete disrobing of the patient, 2) immediate copious irrigation of the area with tepid water, 3) an attempt to identify the offending agent, and 4) treatment of systemic toxicity when present. It is important not to delay initiation of irrigation in order to search for a neutralizing agent. This is time-consuming and delays the critical step of decontamination. Neutralization also produces an exothermic reaction that can cause thermal injury and is therefore not recommended. Sterile irrigating solution is not necessary. After performing these initial stabilizing measures, there are a variety of methods to precipitate and eliminate the fluoride ion and prevent progressive tissue destruction. The best method to use in each case depends on the severity and location of the burn.
Table 1. Summary of Treatment Exposure
for Hydrofluoric
Acid
1) Decontaminate patient by removing contaminated clothing and flushing exposed areas with large amounts of water. 2) Apply calcium gluconate gel topically. 3) Consider subcutaneous injection of calcium gluconate for symptoms not responsive to topical therapy. Consider intraarterial infusion for severe extremity burns. 4) Anticipate systemic toxicity in exposures involving concentrated acid, or in ingestions. Institute cardiac monitoring. Establish intravenous access. Evaluate calcium, potassium, and other electrolyte levels. Be prepared to treat hypocalcemia with large amounts of intravenous calcium. Consider hemodialysis to treat fluorosis and hyperkalemia.
Dermal Injury Topical therapy. Over the years there has been considerable debate as to the optimal topical treatment of HF burns. Calcium or magnesium gels or pastes, so-called HF burn ointment, have been used since first described by Fredenhagen and Wellman in 1932 (5). Calcium gel can be made by mixing 3.5 g of calcium gluconate with 5 ounces of a water soluble lubricant such as K-Y jelly (1). This results in a gel containing approximately 2.5% calcium gluconate. Calcium gel is not commercially available in the United States. Others have advocated topical treatment with a quaternary ammonium compound such as Zephiran, which is thought to exchange ionized chloride for fluoride ions, resulting in a non-ionized fluoride complex (6). Goodfellow has advocated simple flushing with water and treatment with iced water until the pain subsides (7). However, since this treatment does nothing to arrest the damage being done by the free F- ions, pain relief may be due to cold anesthesia rather than effective treatment. Little controlled research has been done to evaluate the effectiveness of various topical treatments. One such study evaluated the effectiveness of calcium gluconate (2.5%) burn jelly, Zephiran, magnesium ointment, aloe gel, and A&D ointment on experimentally induced HF burns of the hind legs of rats. It finds that calcium gluconate gel is most effective in mitigating the damage caused by concentrated hydrofluoric acid (8). Topical therapy is effective primary treatment after decontamination has been carried out. It is easily administered by the patient or other non-healthcare workers. Some advocate these topical therapies as definitive treatment for minor burns, such as those caused by low concentrations of HF where decontamination is accomplished rapidly. Browne is a strong advocate of topical therapy with calcium gluconate gel (9). He recommends continual massage of the gel into the wound for up to several hours, so long as there is continued pain relief and improvement. Edelman endorses treating such wounds topically for 45 minutes. If there is complete pain relief, then the treatment should be considered adequate (10). A vinyl glove can be used as an occlusive dressing once calcium gel has been applied to hand burns. Parenteral therapy. If pain relief is incomplete or symptoms recur, subcutaneous injections of calcium gluconate are indicated. This modality has been shown to result in dramatic relief of pain and im-
Hydrofluoric Acid Toxicity
provement of lesion appearance (11,12). The injections should be carried out using a 27- or 30-gauge needle. The subcutaneous tissues under the involved skin should be injected from sites on the periphery of the lesion. A dose of 0.5 cc per square centimeter of 10% calcium gluconate is used (13). Although calcium chloride has more milliequivalents per cc of calcium, it is contraindicated for subcutaneous infiltration due to its tissue irritating properties (14). There is a difference of opinion on whether local anesthetic should be used with calcium injections. Pain relief is often immediate from calcium alone. Advocates of withholding anesthetics feel that the return of pain indicates a need for further injectable calcium treatment and prefer not to mask the potential return of symptoms. A study done by Harris and Rumack raised controversy over the agent of choice for subcutaneous infiltration of HF burns (15). An unspecified concentration of HF was used to produce burns in a rat extremity model. They then compared the effects of intradermal and subcutaneous infiltration of calcium gluconate, magnesium sulfate, and magnesium acetate on wound healing. Their results show both magnesium salts to be more effective than calcium gluconate in limiting extension and depth of the wounds. This study has been criticized by Edelman. He points out that although all the salts were used as a 10% solution (weight/volume), because of differences in molecular weights of the compounds the molar concentration of magnesium in the solutions was up to eight times that of calcium (10). No controlled human studies have been performed. The vast majority of clinical experience in treating HF wounds has been with calcium gluconate. It is considered to be the agent of choice at this time (14). Digital and hand burns deserve special mention as they are frequently seen, especially in industrial settings. Because of the lack of subcutaneous space, relatively little solution can be injected without concern for compromise of tissue perfusion. This volume limitation can be a problem in more concentrated HF burns. One half milliliter of 10% calcium gluconate contains only enough elemental calcium to neutralize 0.025 ml of 20% HF (16). Anderson and Anderson advocate a treatment regimen for hand burns emphasizing immediate skin cleansing, topical calcium gel, and subcutaneous injections of calcium gluconate when necessary (1). If pain persisted for more than 30 minutes after using calcium gel, they injected calcium gluconate in the method previously described. A palmar fasciotomy was done on any injected fingertips to avoid potentially dangerous high tissue pressures. Any patient
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with subungual pain or periungual tissue involvement had the nail of that digit removed. They observe that only the patients who required nail excision need regional anesthesia, all others have dramatic pain relief with calcium gel alone or in combination with tissue injection of calcium gluconate. The issue of nail removal when periungual tissues are involved is a controversial one. Edelman is in agreement with the above approach. He supports removal of the nail for subungual pain or discoloration (10). Pegg also states that severe pain under the nail is an indication for nail removal (20), as does Iverson and colleagues (12). In a recent review, the issue is not specifically addressed except to state that removal of the nail is often indicated when subungual tissue is involved (14). However, Roberts and Merigan report good success in treating dilute (less than 10%) hydrotluoric acid burns to the nail area in a more conservative fashion. In their experience these burns do not result in significant tissue destruction, although they can be quite painful. They use topical therapy, with longacting digital nerve blocks for pain control (17). If injections to the nailbed area are required, they suggest a lateral or volar approach under digital anesthesia without nail removal. They do advise nail removal for burns with more concentrated acid. Digital burns involving highly concentrated hydrofluoric acid are a difficult problem. Large amounts of fluoride ion need to be neutralized, but tissue space limits the volume of solution that can be injected. Koehnlein and colleagues were the first to describe intraarterial infusions of calcium gluconate as treatment for severe hydrofluoric acid burns of the limbs (18). This technique avoids the problems of increased tissue pressure encountered when injecting into the hands and digits, while at the same time delivering large amounts of calcium to affected tissues. There are several reports in the literature describing good results with this technique (18-2 1). The basic technique used by Vance and colleagues (19) consists of the following: 1) Percutaneous cannulation of the radial artery with a long catheter; 2) Insertion of the catheter proximally several centimeters into the radial artery for burns to the thumb, index, or middle fingers. Or alternatively, the catheter is advanced proximally into the brachial artery allowing access to the ulnar circulation for burns involving the ring or small finger; 3) Arteriogram to confirm blood supply to the injured area; 4) Infusion of dilute solution of calcium salts with a pump apparatus over a 4-hour period (10 ml of a 10% solution of calcium glucconate or calcium chloride in 40 to 50
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ml of 5% dextrose). If pain from the HF burn returns within a 4-hour observation period, the infusion cycle is repeated as necessary until the patient remains symptom free. Minor complications such as local arterial spasm usually respond to infusion of vasodilators or removal of the catheter (19). Advantages of intraarterial therapy include the ability to deliver large doses of calcium in a relatively painless manner and the avoidance of the need for fingernail removal. Disadvantages include the invasive vascular procedure necessary and the need for hospitalization with monitoring of the infusion.
Ocular Injury
Ocular exposure also warrants special mention. The potential for significant injury to this organ is great. Care must be taken not to cause additional iatrogenic damage. McCulley and colleagues report that many of the topical modalities used to treat skin burns effectively cause injury to the eye experimentally. In a rabbit model, irrigation with Zephiran or Hyamine or subconjunctival injections of 10% calcium gluconate each causes injury to normal eyes. Immediate, one-time irrigation with water, isotonic saline, or magnesium chloride is found to be effective and nontoxic. Repeated irrigation causes an increase in corneal ulceration. Irrigation with isotonic calcium chloride also causes an increase in cornea1 ulceration (22). Trevino and colleagues recommend 1% calcium gluconate in saline as an irrigant, followed by instillation of 1% calcium gluconate drops every 2 to 3 hours for several days (23). Browne also recommends use of calcium gluconate drops (9). There have been no controlled studies to support or refute this recommendation. After irrigation, instillation of anesthetic drops to relieve pain and cycloplegics to dilate the pupil may be indicated (24,25). Steroid drops have also been advocated to lessen fibroblast formation in the cornea (23,24). Prompt ophthalmologic consultation is indicated.
Systemic Toxicity
Systemic fluorosis can be a concern with any significant exposure. Systemic toxicity has been reported after ingestion of sodium fluoride, inhalation of HF vapors, and in skin burns. There are numerous case reports in the literature documenting the lethality of such exposure, including one case of homicide reported in the forensic medicine literature (26).
John C. Bertolini
Mayer and Gross reported fatal systemic fluorosis from a 70% HF burn involving 9% to 10% BSA on the lower extremities in a healthy 23-year-old male (27). The patient was immediately undressed, washed in a shower, and transferred to a local emergency department. Several hours later he developed ventricular fibrillation that responded to defibrillation and lidocaine. He was then transferred to a tertiary center, 6 hours after the exposure. The patient experienced several episodes of ventricular tachycardia and developed cardiovascular collapse 11 hours post exposure. A serum calcium determination available at that time was 3.3 mg%. Despite a total of 5 amps of calcium chloride and aggressive resuscitation efforts, the patient expired 17 hours post exposure. Greco and colleagues report three cases of severe fluorosis with hypocalcemia following concentrated hydrofluoric acid burns (28). All of the patients had admission calcium levels of 4.1 mg% or below, one despite administration of subcutaneous and intravenous calcium prior to serum determination. Two patients survived, both after exposure to 70% acid. One received 113.2 mEq of calcium after a 2.5% BSA burn of the face and neck. The other received a total of 266.7 mEq after a 22% BSA injury involving scalp, neck, shoulders, torso, and extremities. The latter is equivalent to 57 amps of 10% calcium gluconate or 19 amps of calcium chloride. Tepperman described a fatal 2.5% BSA burn of the face with anhydrous HF acid in a refinery worker (29). The patient developed ventricular fibrillation approximately 5 hours after injury and died several hours later. Admission serum calcium was 3.5 mg/ dL, just prior to his first dysrhythmia. Despite receiving 280 mEq of calcium over the subsequent few hours, the serum calcium never rose above 3.1. Although this burn involved the face, there was no evidence of airway burn observed during endotracheal intubation. Thus, it was postulated that the systemic toxicity was due solely to dermal absorption of fluoride. There was no clinical evidence of hypocalcemia in the form of tetany. There was, however, mild prolongation of the Q-T interval on ECG. Buckingham describes a 5% BSA burn to the forearm that resulted in bradycardia, QT prolongation, and ventricular fibrillation. Admission serum calcium was noted to be 3 mEq/L. The patient responded transiently to “large” doses of intravenous calcium, but then deteriorated. The decision was made to excise the wound operatively to stop systemic absorption of F- ion, and the patient recovered (30). Tetany was specifically looked for on several occasions and was absent. Chan and colleagues reported on two workers who
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Hydrofluoric Acid Toxicity
died from burns and inhalation of vapors shortly after being exposed to 70% hydrofluoric acid (31). They were splashed with the liquid when a hose being used to unload a tank truck came loose. The authors commented on the lack of effective therapy for massive HF exposure and the need for protective clothing and self-contained breathing apparatus for workers dealing with concentrated HF. The literature also contains reports of systemic toxicity and death following oral intake of fluoride compounds. Yolken and colleagues describe a pediatric ingestion of a commercial laundry powder (32). Abukurah and colleagues reported the ingestion of an insecticide containing sodium fluoride in a suicide attempt (33). Both patients survived after stormy hospital courses including multiple episodes of ventricular fibrillation and treatment with large doses of parenteral calcium. These cases demonstrate that very small cutaneous burns from concentrated HF can rapidly become fatal. Severe hypocalcemia and systemic fluorosis (when fluoride levels are obtained) are the hallmarks of severe poisoning. In the majority of the cases, clinical evidence of hypocalcemia such as tetany, Chvostek’s sign, and Trousseau’s sign are absent. Therefore, all patients with significant exposures need to be placed on cardiac monitors, have intravenous access established, and have rapid and serial evaluation of calcium and other electrolyte levels. Electrocardiographic changes, such as Q-T prolongation, may provide valuable evidence of hypocalcemia. A Q-T prolongation on the ECG due to hypocalcemia is well recognized. It is of interest that major texts do not mention ventricular fibrillation as a manifestation of hypocalcemia (34,35). In Rosen’s text, it is stated that myocardial tetany occurs prior to the development of complex dysrhythmias (34). In the majority of cases discussed above, ventricular fibrillation was seen.
The tendency of severely poisoned patients to die in ventricular fibrillation may be due to the direct toxicity of the fluoride ion on the myocardium (27,36). The role of fluoride-induced hyperkalemia in fatal hydrofluoric acid exposures has also been questioned (36). In a canine model, it has been shown that fluoride poisoning produces hyperkalemia and that lethal ventricular dysrythmias are temporally more closely related to this event than to the development of hypocalcemia (37). When treating systemic toxicity from hydrofluoric acid exposure, the clinician should be prepared to administer intravenous calcium early and in large doses. The induction of metabolic alkalosis with sodium bicarbonate will enhance renal excretion of the fluoride ions (38). Fluoride can also be removed by hemodialysis or cation exchange resins (37,39). Hemodialysis will treat the hyperkalemia that some feel is an important factor in the development of dysrhythmias. Removal of fluoride may be the most important intervention in the treatment of the systemically ill patient (36,37).
SUMMARY Hydrofluoric acid has the potential to cause significant injury due to the unique toxicity of the dissociated fluoride ion. Calcium salts have proven to be effective therapy in treating such injuries. New methods of delivery such as intraarterial infusion have improved the prognosis of severe extremity burns. All emergency physicians need to be aware of the potentially life threatening systemic manifestations of significant burns and their treatment.
author thanks Keith Ghezzi, for his thoughtful comments and editorial review.
Acknowledgments-The
MD,
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