CALL US...TM

The Official Newsletter of the California Poison Control System

 

Volume 8, Number 1
Spring 2010

 

 

Hydrofluoric Acid and Fluorides

 

Introduction

Hydrofluoric acid (HF) is a corrosive agent with unique chemical properties that set it apart from other caustic agents.  Elemental fluorine is the most electronegative of all elements, a property that lends to the many industrial applications of HF and other fluoride-containing compounds as well as to its unique toxicity.  Not only does HF behave like other acids and is capable of causing caustic injuries - the severity of which is proportional to the acid-strength and duration of exposure - but it can cause systemic toxicity as well.  Severe toxicity and death have been described after dermal exposures as small as 2.5% total body surface area with anhydrous (100%) HF.  Other agents containing fluoride include sodium fluoride (NaF), ammonium biflouride, and sulfuryl fluoride.

 

Case Presentation

A 23 year old male graduate student working in a materials science laboratory was etching silicon wafers with 10% HF when he noticed his left forearm began to sting.  This sensation progressed to a burning feeling over the course of about one hour, after which he noticed that the affected area had become erythematous with an area of central pallor.  Being trained in the hazards of HF use, he immediately decontaminated the affected skin with running water, applied calcium gluconate gel onto the affected area, and quickly sought medical attention. 

 

Upon presentation to the emergency department (ED), he had normal vital signs, and his review of systems was negative except for a persistent burning sensation on the volar aspect of his forearm.  His pain, initially rated as a 7/10, had improved to 2/10 since applying the calcium gluconate gel prior to ED arrival.  Dermal evaluation revealed a 6cm x 2cm erythematous area on the volar aspect of his left forearm.  The area was tender to palpation, with a 1cm x 1cm area of central pallor.  Total body surface area of the exposure was estimated to be < 1%.  His ECG demonstrated normal sinus rhythm at 78 bpm, QTc 424, QRS 88, no ST elevations or depressions, and normal-appearing T-waves.  Serum electrolytes were within normal limits, including normal serum and ionized calcium concentrations.  The patient was monitored in the ED for another 6 hours, during which his pain continued to improve. 

 

He was discharged with 1) instructions to apply calcium gluconate gel liberally to the affected area until the burning sensation permanently subsided, 2) primary care and occupational medicine follow up, and 3) instructed to return to the ED immediately for symptom recurrence.  He did not require outpatient referral to a burn specialist.

 

 

Questions:

 

1.  What are the primary mechanisms of hydrofluoric acid toxicity?

 

2.      What findings in this case are most reassuring that the patient is unlikely to develop systemic toxicity?

 

3.      What treatments are available for HF exposures?

 

Epidemiology

Hydrofluoric acid is the most common source of fluoride exposures.  It was first used artistically to etch glass in 1670, and has since found use in many applications ranging from household rust removal to the semiconductor industry.  While present in many industrial sources, it is most often associated with processes requiring strong corrosive and oxidizing agents.  Industrial applications utilize HF in concentrations ranging from 1-100% (Table).  Although less available now, ammonium bifluoride was a popular rust stain remover that is converted to HF in acidic stomach contents.  Sulfuryl fluoride

(SO­2F2, ex. Vikane), a common anti-termite fumigant, is also a potential source of inhalational fluoride exposures.

 

Liquid forms and common concentrations of hydrofluoric acid

Form

Concentration (%)

Anhydrous

100

Aqueous

70

Reagent grade

5-52

Commercial products

  -rust/stain remover, propellants

  -leather tanning 

0.5-70

Household

8

 

 

Pathophysiology

Hydrofluoric acid (HF) is classified as a weak acid that is roughly 1000 times less dissociated in water than an equimolar solution of HCl.  However, as the most electronegative element on the periodic table, free fluoride ions (F-) avidly bind available cations, the most physiologically important being calcium and magnesium.

 

After dermal or mucosal contact, HF penetrates deeply into tissues prior to dissociating into hydrogen ions and fluoride ions.  Once dissociated, the free fluoride ion sequesters both intracellular and extracellular Ca2+ and Mg2+ ions.  Fluoride can inhibit Na+/K+ ATPase primarily on red blood cells leading to a delayed onset of potentially life-threatening hyperkalamia.  The fluoride ion itself likely has direct cardiotoxic effects.  Significant hypocalcemia or hypomagnesemia early after an exposure reflect systemic toxicity and both can lead to QT interval prolongation and dysrhythmias including the classic prolonged QT interval dysrhythmia torsade de pointes.  The QT interval on the cardiac monitor or ECG can be used as a rapid screen for the potential presence of hypocalcemia or hypomagnesemia.

 

Clinical Presentation

No routinely available diagnostic test exists to confirm fluoride exposure in the acute setting.  In general, the diagnosis is based upon a history of exposure, physical examination, and electrolyte abnormalities.  Fortunately, HF possesses good warning properties; the time-to-onset of pain after cutaneous exposure is proportional to the concentration of the offending agent.  Dilute solutions

(< 20%) rarely produce immediate symptoms, while concentrated solutions (>50%) result in immediate pain.  Significant pain despite the lack of significant skin changes after an exposure to a liquid is a clue to an exposure to HF or another fluoride containing substance. 

 

Exposure severity is a function of multiple variables, including route, concentration, size of affected area, and contact time.  While there is no consensus within the literature as to the combination of acid strength and total body surface area that together constitute a significant exposure, estimates have been derived from clinical experience and a review of case-report fatalities.  Systemic hypocalcemia, hypomagnesemia, and hyperkalemia may occur after 1) any hydrofluoric acid ingestion or inhalation, or 2) dermal exposures with greater than 1.0% body surface area burns with solutions concentrated to

> 50%.  It is useful to remember that an area the size of the patient’s palm approximates 1% total body surface area.

 

Skin.   Dermal exposures typically occur in the occupational setting via small defects in rubber gloves, or spills onto unprotected skin.  Initial manifestations include pain, erythema, and blanching, but edema and necrosis have been described after concentrated exposures.  Often the pain is out of proportion to the benign appearing dermal changes. Beyond excruciating pain, HF readily penetrates deeply and can cause tissue necrosis and even bone desorption.   Like any other burn, full-thickness tissue loss can occur and may ultimately require skin grafting.  Referral to a burn specialist should be determined on a case-by-case basis.

 

Inhalation.  Concentrated or pressurized HF can explode or result in splashes onto the face, leading to inhalational exposures.  Death has been described after a 3-hr exposure to sulfuryl fluoride gas, and after several instances of facial exposures to concentrated HF with concomitant inhalational exposure.  Pronounced irritant effects tend to be immediate, and include ocular and nasopharyngeal irritation, laryngospasm, and bronchospasm.  Like dermal exposures, systemic effects tend to be delayed, but time to onset of effects tends to be inversely related to the concentration of the offending agent.

 

GI.  All ingestions involving fluoride-containing compounds should be managed aggressively, as systemic toxicity and death is likely.  Soon after exposure, suction of stomach contents should be considered.  Oral calcium or magnesium salts such as a calcium-containing antacid should be provided to bind any free fluoride within the GI tract.  Systemic toxicity is likely and all patients should have cardiac monitoring.  Gastrointestinal burns or perforation are possible and consultation with a gastroenterologist or surgeon is warranted.  Caustic esophageal injuries can lead to perforation and stricture formation.

 

Ocular.  Eye exposures should also be treated aggressively with copious normal saline irrigation and immediate ophthalmology consultation.  The role of calcium-containing irrigation solutions is controversial. 

 

Treatment – Calcium Replacement

Calcium and magnesium should be checked when there is any potential for systemic toxicity and replaced as necessary.  Calcium rapidly precipitates fluoride ions and is an effective antidote for dermal exposures and systemic hypocalcemia resulting from fluoride absorption.  Depending upon the type and severity of exposure, calcium can be administered topically, subcutaneously, intravenously, or intra-arterially. 

 

 

Dermal Exposures: 

Topical calcium gels can either be purchased, like Calgonatẻ, or easily made by crushing calcium carbonate antacid tablets into a water-based gel.  Commercially available gels are commonly found in industrial settings that utilize HF (as in the case-vignette), and patients may arrive with calcium gels already applied to the skin.  For hand exposures, the gel can be placed inside a latex glove, which serves as a convenient and efficient occlusive dressing, and can be replaced several times a day as needed for recurring pain.  Persistent pain or lack of improvement should prompt consideration of subcutaneous, intravenous, or intra-arterial calcium therapy.

 

Subcutaneous injection should be considered when topical treatment fails to relieve pain.  Inject 5–10% calcium gluconate (not calcium chloride as it is itself caustic) intralesionally and perifocally (0.5–1 mL/cm2 of affected skin), using a 27-gauge or smaller needle. This can be repeated two to three times at 1- to 2-hour intervals if pain is not relieved by initial injection. No more than 0.5 mL should be injected when treating digital exposures.  A small amount of lidocaine can be added to the injected solution for further pain relief.

 

Localized intravenous calcium administration (Bier block) is another treatment that can be utilized for hand or other distal extremity HF burns.  An IV catheter is placed in the distal part of the extremity, such as the hand for finger burns.  Blood is exsanguinated from the distal extremity using a wrap dressing or by elevating the extremity.  A blood pressure cuff is then applied to the proximal aspect of the extremity and inflated to greater than systolic blood pressure.  Intravenous calcium is now infused in the distal IV; we have used 1 gram of calcium gluconate diluted in NS to 40 mL in this technique, infused slowly.  The blood pressure cuff remains inflated for up to 15 minutes but distal pain or discomfort may limit inflation time to shorter periods.  This technique can be repeated every 6-12 hours if needed for pain.    

 

Intra-arterial calcium administration can be used to treat serious hand/digital injuries.  Dilute 10 mL of 10% calcium gluconate with 50 mL of D5W and infuse over 4 hours through either a brachial or radial artery catheter. The patient should be monitored closely over the next 4–6 hours, and if pain recurs, a second infusion should be given. Some authors have reported 48–72 hours of continuous infusion.

 

Systemic intravenous calcium should be used if systemic hypocalcemia or hyperkalemia develops. Calcium gluconate 10%, 0.2–0.4 mL/kg IV, or calcium chloride 10%, 0.1–0.2 mL/kg IV (if a secure central line is available), should be given liberally when symptomatic hypocalcemia occurs.

           

 

Discussion of Case Questions

 

1.      What are the primary mechanisms of hydrofluoric acid toxicity?   Hydrofluoric acid can cause toxicity from both its direct caustic effects on contacted tissue, and potentially via multiple mechanisms that can result in systemic toxicity in significant exposures.  Absorbed fluoride can result in life-threatening hypocalcemia or hypomagnesemia by binding to calcium and magnesium.  Additionally, interactions with Na+/K+ ATPase on red blood cells can lead to delayed life-threatening hyperkalemia.  Further, fluoride itself likely has direct adverse effects on the heart as delayed onset of fatal dysrhythmias have been described despite normal calcium, magnesium, and potassium concentrations.  The presence of significant hypocalcemia or hypomagnesemia after an exposure reflects serious systemic toxicity.

 

2.      What findings in this case are most reassuring that the patient is unlikely to develop systemic toxicity?  Low-concentration exposure on a small body surface area, easily controllable pain, normal vital signs, a normal QTc interval, and a normal serum calcium. 

 

3.      What treatments are available for HF exposures?  Calcium.  Topical calcium gluconate/chloride gels, intravenous calcium gluconate (or calcium chloride via central line), subcutaneous calcium gluconate, Bier block, or intra-arterial calcium gluconate.  Initially, copious irrigation should be done of the affected area. For ingestions, naso-gastric suction of liquid HF should be considered if early after presentation given the high potential for life-threatening systemic toxicity.  Magnesium can be used in a similar method as calcium given orally or IV.  For exposures in which significant systemic toxicity is occurring and dysrhythmias imminent, amiodarone administration may prevent the potassium efflux from red blood cells.  Hemodialysis may also be considered as it can help treat the electrolyte abnormalities and potentially remove the absorbed fluoride.

 

CONSULTATION ASSISTANCE

Consultation with a specialist in poison information or with a medical toxicologist can be obtained free of charge by calling the California Poison Control System at 1-800-222-1222.

This issue of CALL US... was written by Joshua Nogar, MD

CALL US... is published by the California Poison Control System. Editorial Board: Executive Director, Stuart E. Heard, PharmD; CPCS Medical Directors: Timothy E. Albertson, MD, Richard F. Clark, MD, Richard Geller, MD, Kent R. Olson, MD; CPCS Managing Directors: Judith Alsop, PharmD, Thomas E. Kearney, PharmD, Lee Cantrell, PharmD.  Assistant Editors: Binh Ly, MD, Cyrus Rangan, MD, Chris Tomaszewski, MD, and Aaron Schneir, MD. Editor: Richard F. Clark, MD.

The California Poison Control System is operated by the School of Pharmacy, University of California, San Francisco.  (callus@calpoison.org)