Hydrofluoric Acid (HF)                                                                                                                                              Revised 12/09

Introduction

HF is the inorganic acid of elemental fluorine.  It is produced from the reaction between calcium fluoride and sulphuric acid to produce HF gas which is cooled and stored as a liquid.  It has many industrial uses such as etching and polishing glass, cleaning stone, brick and marble, and in the manufacture of pesticides, plastics and high octane fuels.  In the home it is found in rust removers, aluminum brighteners and heavy duty cleaners.  Related compounds that have similar toxicity profiles include ammonium bifluoride, ammonium fluoride, potassium bifluoride and sodium bifluoride.  Concentrations of HF vary greatly and have profound impact on clinical outcome: the HF used for industry may approach 100% (aka anhydrous HF) whereas the concentration in household cleaners is typically 5 - 8%.  The fluoride in toothpaste is stannous fluoride or sodium monofluorophosphate and is of very low toxicity.


Toxicity

HF is a particularly dangerous acid because of its unique ability among acids to penetrate tissue.  The reason for this is the high electronegativity of the fluoride anion which holds onto the hydrogen cation tightly.  The result is a weak acid that exists predominantly in the undissociated state compared to other acids (1000 times less dissociated vs hydrochloric acid).  In the undissociated state the HF molecule is able to penetrate skin and soft tissue by non-ionic diffusion.  Once in the tissue the F anion is able to dissociate and cause liquefactive necrosis of soft tissue, bony erosion, as well as extensive electrolyte abnormalities by binding the cations Ca2+ and Mg2+.  This is unusual among acids which typically cause damage via the free H cations resulting in coagulative necrosis and poor tissue penetration.  The ability to penetrate tissue is why HF can cause severe systemic toxicity from even relatively small dermal exposures and why exposure to this compound should be treated with extreme caution.  The amount of toxicity depends, like every other toxin, on four factors: 1. concentration of the agent 2. the route of exposure 3. the length of exposure and 4. the amount of surface area affected.  These factors should also be considered with any co-morbidities the patient may have in determining severity of the poisoning and the type of treatment to be given.  The following are the most common types of HF exposures and their clinical presentations:

Dermal 

This is the most common type of exposure to HF with the digits being the most often affected body part.  The presentation can vary significantly depending on the concentration of the HF to which the patient was exposed.  HF concentration of >50% causes immediate pain on contact with skin.  The skin will become erythematous within minutes and blistering and edema will occur within 1 - 2 hours. Severe burns will have a central grayish area of coagulative necrosis like a typical acid burn.  There are no household products with HF concentrations that high so this will almost always be an occupational exposure.  Patients exposed to HF concentrations from 20 - 50% may take 1 - 8 hours for erythema and pain to develop at the site of contact, and exposures to concentrations < 20% may take more than 24 hours to become symptomatic.  One must be very careful not to underestimate burn severity and potential for serious complications by a paucity of symptoms early on or from a relatively small area of exposure.  There have been reported fatalities due to HF exposure with as little as 2.5% BSA (body surface area) affected.  The following are suggested guidelines for determining who is at high risk for serious complications from a dermal exposure
1% BSA (size of hand) with HF concentration of 50% or higher
Burns to face or neck (any concentration) because of risk of inhalation
5% BSA of any HF concentration
One of the characteristics of HF exposure to skin is pain out of proportion to appearance of the burn.  This is thought to be due to the fluoride anion binding to Ca2+ ions in the tissue which causes an efflux of potassium which stimulates nerve endings.

Inhalation 

 HF is a volatile liquid with a boiling point of only 19.5 C (67.1 F).  Its volatility makes it a high risk compound for inhalation injury.  Severity can range from mild airway irritation to severe burning and dyspnea.  With inhalation of HF concentrations > 50% there is a significant risk that they will develop pulmonary edema/ARDS and pulmonary hemorrhage.  One must assume inhalation injury in burns involving face and neck, burns > 5% BSA and burns with HF concentration > 50% even if the patient is initially only mildly symptomatic.  Soaked clothing is also a strong predictor of inhalation injury.  All inhalation injury patients are at high risk for systemic complications.
Ingestion 
All ingestion injuries are potentially fatal from systemic complications.  The patient is likely to have acute nausea, vomiting and abdominal pain.  Besides the systemic risks the patient is also at risk for viscus perforation and hemorrhagic gastritis.  It is estimated that the minimal toxic dose from ingestion is 5 - 10 mg/kg and the minimal lethal dose is 15 - 30 mg/kg.

Ocular 

Ocular exposure is due to exposure to vapors or to splash injury.  While by itself is not likely to cause systemic problems, one must be suspicious of concomitant inhalation injury or face burn injury in these patients.  Patients may have little complaint early on, some will have pain almost immediately depending on the type of exposure and concentration.  Complications of eye exposure include corneal opacification, corneal sloughing, keratoconjunctivitis and necrosis of the anterior chamber.
Systemic
It is HFs potential for lethal systemic complications that distinguishes itself from other acids that are unable to penetrate tissue so effectively.  Systemic problems arise predominantly from the serious metabolic derangements that occur due to the fluoride anion.  Specifically, fluoride anion complexes with the tissues stores of Ca and Mg leading to profound hypocalcemia, hypomagnesemia, hyperkalemia, and metabolic acidosis.  The fluoride anion is furthermore directly toxic to a number of cellular enzymes and metabolic processes.  The hypocalcemia and hyperkalemia can lead to cardiac arrest and death due to refractory ventricular fibrillation and torsades de pointes.  One case report is that of a 23 year old male who was splashed with 70% HF on 10% of his body whose calcium on arrival to the ED was 4.3 mg/dl.  Despite repeated IV calcium replacement he went into cardiac arrest and asystole from which he could not be resuscitated.  HF poisoning also can have deleterious effects on hepatic and renal function as well.

Treatment

The goal of treatment in any case of HF exposure is to react promptly to minimize local tissue injury and destruction while at the same time monitoring for and treating any systemic effects of the exposure.  The following represent the modalities of therapy that are most consistently condoned and employed based on the recent literature for the various type of exposures.  In all cases of true HF exposure, or the closely related products mentioned above, a visit to the ED is indicated because of the insidious nature of the poison and the potential for lethal outcome from apparently minor injury.

Dermal Injury Treatment 

Decontamination: Therapy begins with removal of any contaminated clothing and irrigation with copious amounts of water for at least 20 minutes.  This should occur prior to transport to a health care facility as this step is the most important in minimizing tissue penetration and systemic consequences.  Do not waste time looking for a neutralizing solution.  Many authorities recommend that the patient take an oral calcium supplement during this initial lavage process as it is unlikely to harm the patient and may well help slow the progression of the hypocalcemia.  All of the treatment steps after this one are various methods of precipitating the fluoride anion and preventing progressive tissue destruction.
Topical Calcium gluconate gel (Mag gluconate gel if Calcium is not available): The theory behind this is that as the calcium is massaged into the tissue it will complex with the fluoride anion and precipitate out as a salt thus preventing the fluoride from scavenging all of the body'­s needed calcium stores.  It further prevents the fluoride anion from exerting its directly toxic effects on cellular processes.  Place 3.5 g of calcium gluconate powder into 5 oz of KY (or other water soluble gel) and massage into skin for at least 30 minutes. Alternatively, one may use 25 ml of 10% calcium gluconate and 75 ml of KY.  This effecively creates a 2.5 % calcium gluconate gel. Studies have demonstrated this as an effective technique.  If calcium gluconate is unavailable, one may employ 3.48 g of Mg gluconate and 5 oz of KY in a similar manner.  Immersion in Zephiran (0.13% benzalkonium chloride) may be considered as well.  Effectiveness of this modality is based on relief of pain, which is why local anesthetics are used only when a digital block is needed for nail removal.  If pain is largely unrelieved by this technique after 1-2 hours then one should proceed to infiltration as well as reapply more gel to burned area.  Also of note is that DMSO is sometimes used to increase Ca penetration.
Local Subcutaneous infiltration of Ca gluconate: is indicated in burns where there is a central grey area of coagulative necrosis (indicating severe burn), severe throbbing pain, or when topical therapy fails to alleviate the pain.  Using a 27 to 30 gauge needle, one injects 0.5 ml of 10% Ca gluconate subcutaneously for every square centimeter of burn.  Do not substitute CaCl as this is damaging to the tissue.  In general, one rarely needs to employ this technique if the exposure was to HF of concentration less than 20%.  This can be a difficult technique to perform in the fingertips because there is little room subcutaneously for such a large amount of infiltration.  One must be cautious of causing pressure necrosis from this technique in any area where there is little room for infiltration of such volumes of fluid.  It is sometimes necessary to remove the fingernail in a patient for this to be effective, and while there is no universal agreed upon indication as to when it is most appropriate to remove the nail, a reasonable approach would be to remove the nail if there is severe subungual pain and discoloration.  When a nail is to be removed a digital block with lidocaine is indicated.  When burns are severe, or when the digits are involved and it is not possible to adequately infiltrate due to risk of pressure necrosis then one can proceed to the next intervention - arterial infusion.
Arterial infusion of Ca gluconate: The method is indicated with severe distal extremity burns by those physicians who are comfortable with the technique.  The technique is to catheterize the brachial artery if the little or ring finger is involved, or radial artery if the burn is confined to the thumb, index or middle finger and to infuse 10 ml of 10% Ca gluconate in 40 ml of D5W over 4 hr. Some protocols suggest getting an angiogram confirming placement of catheter, others only if placement was difficult.  If pain is present after the 4 hr then repeat the infusion until the pain is gone.
The role of surgery:  There is no universal protocol for involving a plastic surgeon in an HF burn case. In general, it is considered unnecessary if standard medical therapy is begun promptly, particularly as infusion has been shown to help apparently non-viable tissue to recover.  However, there are cases where medical therapy failed to halt the progression of the fluoride poisoning and surgical excision proved to be the only effective therapy.  A scenario when surgery should be considered early is when the burn is severe, i.e. there is a 100% HF burn of > 5% BSA.  Consulting a surgeon in such cases would be prudent. 

Inhalation Injury Treatment 

As mentioned previously, these patients are at high risk for developing systemic complications from their exposure as well as specific pulmonary complications such as pulmonary edema and hemorrhage.  The first line of therapy is 100% O2 by face mask, with an eye toward the need for possible intubation and positive pressure ventilation if ARDS develops.  Administration of nebulized 4 ml of 2.5% Ca gluconate (1mL of 10% Ca gluconate with 3mL of normal) has been recommended.  Also endotracheal instillation of calfactant in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality.

Ingestion Injury Treatment

As with the inhalation injury, the risk for systemic complications is great.  Electrolyte disturbances, dysrhythmias, and death have occurred following ingestion of 3 oz of 6-8% HF.  Death has been reported after ingestion of 15mL of 9% HF (see Systemic treatment). Treatment is largely supportive.  DO NOT induce emesis as this increases the risk of aspiration.  If ingestion is recent, < 1 hr, then perform gastric lavage using 10% Ca gluconate as dilutent.  Otherwise give milk, chewable calcium carbonate tablets or milk of magnesia.  Placement of a nasogastric tube can make speed the effectiveness of this treatment.  Consult a gastroenterologist and a general surgeon early because there will likely be a need for endoscopy, and there is an increased risk of viscus perforation.

Ocular Injury Treatment 

Treatment of ocular chemical exposure begins with copious irrigation with water as soon as possible after the exposure and should continue for 30 minutes.  One may substitute normal saline or lactated ringers if available immediately.  Do not repeat this irrigation as there is a reported increased rate of corneal damage from repeated irrigation.  Similarly, there is no role for calcium gel or infiltration with ocular injury.  Some recent studies have shown a benefit of topical 1% Ca gluconate drops every 2 - 3 hours in the affected eye for several days.  Cycloplegics are also indicated if needed for comfort.  It is important to get an opthalmology consult early in cases of ocular exposure to HF, even if the patient is asymptomatic.

Systemic toxicity Treatment 
 
Again, it is the peculiar ability of HF to penetrate tissue that allows the fluoride anion to cause such profound and potentially lethal metabolic derangements, the most notable being severe hypocalcemia. Any patient with inhalation injury, ingestion, ocular injury, burns to face or neck, >1% BSA of >50% HF, or >5% BSA of any HF concentration should be considered as having the potential for systemic consequences from their exposure.  All such patients need to be on a heart monitor, have a 12 lead EKG, and labwork drawn including calcium, magnesium, metabolic panel, and liver function tests. Fluorine levels are not indicated unless exposure is of a chronic nature. If the exposure was significant then one should begin IV Ca replacement without waiting for labs to return.  A common starting point is to give 2 to 3 ampules of 10% CA gluconate IV SLOWLY (2-5min per ampule) and then base treatment on hourly Ca levels.  Case reports show that some patients required over 100 mEq of calcium before the hypocalcemia resolved, and so repeated doses are often necessary.  Furthermore, in many instances there is no clinical evidence of hypocalcemia such as tetany, Chvostek'­s or Trousseau's signs.  The most rapid way to assess for the presence of hypocalcemia is with the EKG where a prolonged QT will often be present.  Many advocate giving MgSO4, 2-4 g over 20 minutes in addition to the calcium.  If panel demonstrates an acidosis, NaHCO3 IV is helpful in eliminating the fluoride anion in the urine and resolving the metabolic acidosis.  At present there is no agreed upon role for dialysis unless the patient has underlying renal dysfunction prior to the exposure.  The most lethal consequences of this systemic metabolic derangement are ventricular dysrrhythmias - particululary vendtricular fibrilatiion and torsades do pointes.  Rapid replacement of calcium, magnesium and correction of the metabolic acidosis with fluids and bicarbonate are important steps to try to prevent the occurrence of these dysrrhythmias which can be refractory to resuscitation.  Because amiodarone has potassium channel block effects, it may be the preferred antidysrhythmic in the setting of hydrofluoric acid poisoning.

Conclusions
Hydrofluoric acid burns are very dangerous and thankfully rare in the United States.  What makes them especially dangerous is their sometimes innocuous appearance early on.  This can lead patients to delay coming to the hospital and health care workers to underestimate how sick the patient truly is.  Any confirmed exposure to HF, ammonium fluoride, ammonium bifluoride, potassium bifluoride, and sodium bifluoride should be evaluated in the ED.  Health care workers must be careful to take barrier precautions to avoid exposure to themselves.  Rapid removal of the agent and prompt visit to the hospital are important steps the patient can take to help minimize injury.  For physicians, toxicologists, nurses and other health care personnel, early aggressive treatment of local tissue damage and appropriate vigilance for systemic sequelae are the keys to reducing morbidity and mortality.

References
1.Bertolini, JC. Hydrofluoric Acid: A Review of Toxicity.  Journal of Emergency Medicine, Vol 10 pp 163 - 168, 1992.
2. Bosse GM, et al. Delayed Toxidromes.  Journal of Emergency Medicine; 1999 Jul - Aug, 679 - 690.
3. Goldfrank LR et al.  Toxicologic Emergencies, 8th ed.  2006, Appleton and Lange.  pp 1417 - 1423.
4. Kirkpatrick JJR, et al. Hydrofluoric Acid Burns: a Review.  Burns, vol 21, No. 7 pp 483 - 493, 1995.
5. Perry HE.  Pediatric poisonings from houshold products: hydrofluoric acid and methacrylic acid.  Current Opinion in Pediatrics.  13(2) : 157 - 161, 2001 April.
6. Olson KR, et al.  Poisoning and Drug Overdose, 5th edition.  Appleton and Lange, 2007.  pp 222 - 224.
7. Sheridan RL, et al.  Emergency Management of Major Hydrofluoric Acid Exposures.  Burns, 1995, Vol 21, No. 1, 62 - 64.
8. Tsonis L, Hantsch-Bardsley C & Gamelli RL: Hydrofluoric acid inhalation injury. J Burn Care Res 2008; 29(5):852-855.
9. Wilson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury. A randomized controlled trial. JAMA 2005; 293:470-476.