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Three Part Question

In [patients with hydrofluoric acid burns to the eye] is the use of [Hexafluorine more effective than the conventional treatment of water irrigation or calcium gluconate] at [reducing severity and improving outcome]?

Clinical Scenario

A 31-year-old man was working in a local chemical factory when he splashed himself with hydrofluoric acid to the eye. He attends the emergency department and you arrange for copious water irrigation and oral pain relief. You have the heard about the Hexafluorine antidote solution and wonder whether there is any evidence for its use.

Search Strategy

Calcium gluconate versus water irrigation
Medline search from 1946-06/2012 using the OVID interface.
Searched – {(Hydrofluoric acid OR Hydrofluoric acid burn* OR HF) AND (eye* OR ocular) AND (calcium gluconate).mp.} LIMIT (English)

Embase search from 1974-06/2012 using the OVID interface.
Searched – {(Hydrofluoric acid OR Hydrofluoric acid burn* OR HF) AND (eye* OR ocular) AND (calcium gluconate).mp.} LIMIT (English)

The Cochrane Library
Searched – (Hydrofluoric acid) AND (calcium gluconate)

Hexafluorine versus calcium gluconate versus water irrigation
Medline search from 1946-06/2012 using the OVID interface.
Searched – {(Hydrofluoric acid OR Hydrofluoric acid burn* OR HF) AND (eye* OR ocular) AND (Hexafluorine).mp.} LIMIT (English)

Embase search from 1974-06/2012 using the OVID interface.
Searched – {(Hydrofluoric acid OR Hydrofluoric acid burn* OR HF) AND (eye* OR ocular) AND (Hexafluorine).mp.} LIMIT (English)

The Cochrane Library
Searched – (Hydrofluoric acid) AND (Hexafluorine)

Search Outcome

Calcium gluconate versus water irrigation – 20 papers were found of which 4 were relevant.
Using the references of the papers already found, another 2 papers were also found to be relevant.

Hexafluorine versus calcium gluconate versus water irrigation- 8 papers found of which 3 were relevant.
1 other relevant paper was found in the references.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
McCulley JP 1990 USA	Rabbits	Experimental animal study	Conjunctival inflammation	Minimal = Saline, Minimal-moderate = MgSO4, MgCl2, Hyamine, Moderate-severe = CaCl2, Severe = Zephiran, calcium gluconate injections	Uncontrolled. Not human data. Results are based on subjective clinical observations.
			Conjunctival chemosis	Minimal = Hyamine, Saline, Moderate = MgSO4, MgCl2, Moderate-severe = CaCl2, calcium gluconate injections
			Corneal stromal opacification	Minimal = Saline, MgCl2, Moderate = CaCl2, Moderate-severe = MgSO4, Severe = Hyamine, Zephira
			Corneal stromal oedema	Minimal = Saline, Moderate = MgSO4 , MgCl2, Hyamine, Severe = CaCl2, Zephiran, calcium gluconate injections
Beiran I 1997 Israel	38 rabbits	Experimental animal study	Corneal erosion	Group 2, 3 and 4 had smaller area of erosion than group 1 after day 1, but after 2 weeks no significant difference except group 4 was significantly worse.	Uncontrolled. Not human data. Results are based on subjective clinical observations. Does not have a group irrigated with calcium gluconate eye drops without the addition of saline.
			Corneal haziness	No significant difference between all groups, but after 2 weeks haziness markedly deteriorated in group 4.
			Conjunctival damage	No significant difference between all groups, but after 2 weeks conjunctival damage increased in group 4.
			Acidity	After HF exposure, pH – 2.5 and after rinsing with all groups, pH – 6 – 6.5
McCulley JP 1983 USA	Rabbits and one male patient	Experimental animal study and a case report	Corneal ulceration	CaCl2 irrigation and injections caused an increase in corneal ulceration.	Uncontrolled. Not human data.
			Toxicity	MgSO4, Zephiran, Hyamin and subconjunctival 10% calcium gluconate injections were all too toxic for the eyes. Water, saline and MgCl2 were found to be non-toxic.
Spöler F 2008 Germany	Rabbits	Experimental animal study	Penetration depth of the acid	Tap water and 1% calcium gluconate managed to slow the acid but couldn’t prevent full penetration; however Hexafluorine stopped the acid penetration.	Uncontrolled. Not human data. It did not take into account the concentration of HF.
			Opacification of the cornea	Tap water and 1% calcium gluconate increase cornea opacification whereas the cornea remained clear after rinsing with Hexafluorine.
Hall AH 2000 France	One male patient	In vitro study and case report	In vitro pH	Water – no effect, 10% calcium gluconate final pH - 4.5, Hexafluorine final pH - 6.5	Does not answer my three part question about HF exposure to the eye specifically. Not human data. Does not compare with water or calcium gluconate irrigation.
			In vitro pF	Water – no effect, 10% calcium gluconate final pF - 3, Hexafluroine final pF - 6

Comment(s)

Different decontamination solutions have been investigated using rabbit’s eyes but there is little appropriate human data. Nevertheless, using in vitro studies, in vivo experimental animal studies and previously reported human clinical cases, Hexafluorine has demonstrated to be the most efficacious irrigator for reducing severity and improving the outcome after HF exposure to the eye.

Clinical Bottom Line

It is imperative to rinse a HF ocular burn as soon as possible in order to prevent or minimise subsequent injury. Hexafluorine has been shown to be the most effective decontamination solution.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. McCulley JP Ocular Hydrofluoric Acid Burns: Animal Model, Mechanism of Injury and Therapy Transactions of the American Ophthalmological 1990; 88: 649-684
2. Beiran I et al. The efficacy of calcium gluconate in ocular hydrofluoric acid burns. Human and Experimental Toxicology 1997; 16: 223-228
3. Bentur Y et al. The role of Calcium Gluconate in the Treatment of Hydrofluoric Acid Eye Burn Annals of Emergency Medicine 1993; 22(9): 1488-1490
4. Rubinfeld RS et al. Ocular Hydrofluoric Acid Burns. American Journal of Ophthalmology 1992; 114(4): 420-423
5. Hatai JK et al. Hydrofluoric Acid Burns of the Eye: Report of Possible Delayed Toxicity. Cutaneous and Ocular Toxicology 1986; 5(3): 179-184
6. McCulley JP et al. Hydrofluoric Acids Burns of the Eye. Journal of Occupational Medicine 1983; 25(6): 447-450
7. Spöler F et al. Analysis of Hydrofluoric Acid Penetration and Decontamination of the Eye by means of Time-Resolved Optical Coherence Tomography. Burns 2008; 34(4): 549-555.
8. Soderberg K et al. An Improved Method for Emergent Decontamination of Ocular and Dermal Hydrofluoric Acid Splashes. Veterinary and Human Toxicology 2004; 46(4): 216-218
9. Mathieu L et al. Efficacy of Hexafluorine for Emergent Decontamination of Hydrofluoric Acid Eye and Skin Splashes. Veterinary and Human Toxicology 2001; 43(5): 263-265
10. Hall AH et al. Hexafluorine for Emergent Decontamination of Hydrofluoric Acid Eye/Skin Splashes. Semiconductor Safety Association Journal 2000; 14: 30-33