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Interest of an active rinsing solution for the decontamination of ocular corrosive splashes Presented at Eurotox 2002, Budapest, Hungary, 15-18 Sept 2002 L. Mathieu (1) , M. Gérard (2) , N. Schrage (3) , S. Langefeld (4) , J. Blomet (1) (1) PREVOR Laboratory, Valmondois, France (http://www.prevor.com); (2) Hospital of Cayenne, Guyana, France; (3) Augenklinik, Aachen, Germany; (4) Brüderkrankenhaus, Trier, Germany. Severe eye burns occur rarely, but are related to a poor prognostic in rehabilitation. An emergency treatment has been identified as a decisive factor for decreasing burns (1), in vitro and in vivo experiments have been performed to show the interest of the use of an emergency active rinsing solution, as Diphotérine ® (2) , in comparison with water and saline solution. The in vitro studies are performed to show the mechanical effect of a rinsing solution, the influence of its hypertonicity (3) and its efficacy of decreasing the aggressiveness of common corrosives. Among the vitro studies described, the first step is to evaluate the efficacy of the rinsing solution on the aggressiveness of a chemical product by a simple dosage of 1 milliliter of a corrosive, sodium hydroxide or hydrochloric acid by an increasing volume of the rinsing solution, Diphotérine versus water. A model of semi-permeable membrane was used to simulate both external and complete rinsing of the eye and cells culture were used to show the influence of hypertonicity on the diffusion and the necrotic effects of corrosives. The following carrying up represents the experiment of the simulation of the external rinsing (Fig. 1) where the pH value is measured each two seconds and the simulation of a complete rinsing (Fig. 2). In this experiment 50 milliliters of sodium hydroxide 1N and 25 milliliters of saline solution (NaCl 0.9%) are put in contact through a semi-permeable membrane. The sodium hydroxide is the chemical aggressor and the saline solution represents an internal physiological compartment. An experimental study (4) on New Zealand albino rabbits was conducted to analyse the delay for ocular rinsing in the treatment of severe ocular burns due to ammonia 15.3%. Two solutions of ocular wash, saline solution and Diphotérine ® were compared. The in vitro and in vivo experiments showed the importance of using an active rinsing solution such as Diphotérine ® (5) . It allowed a quick return to a physiological pH, stopping both the penetration and the aggressiveness of the corrosive. No oedema was observed when a rinsing with Diphotérine ® was used for the decontamination of the ammonia burn and it was observed in the case of saline rinsing solution. (1) Kuckelkorn R, Schrage NF, Keller G et al. Acta Ophthalmologica Scandinavica, 2002, 80, 1, 4-10 (2) Kompa S, Schareck B, Tympner J, Wüstemeyer H, Schrage NF. Graefe's Arch Clin Exp Ophthalmol 2002, 240, 308-313 (3) Josset-P, Meyer-MC, Blomet-J, SMT, 1986, 25-33 (4) Gérard-M, Louis-V, Josset-P, Menerath-JM, Blomet-J, Merle-H J. Fr. Opht 2000, 23, 1-10 (5) Hall AH, Blomet J, Mathieu L. Vet Human Toxicol 2002, 44, 4, 228-231 In vitro experiments 1. COMPARATIVE DOSAGE OF CORROSIVES 2. SIMULATION OF AN EXTERNAL RINSING Results : Only a small volume of Diphotérine ® is needed to return to a physiological pH value where no chemical burn can appear. With the water or saline rinsing, there is no effect on the corrosivity of the chemical product. Results : For both acid (Fig.: 4) and base (Fig.: 5) rinsing, it takes less than 20 seconds to return to a physiological pH value with Diphotérine ® , and about 50-60 seconds to reach the same physiological pH value with a water or saline rinsing. 3. SIMULATION OF A COMPLETE RINSING Results : This experiment (Fig.: 6) shows the effects of the osmotic pressure and absorption properties of the rinsing solution. The results show that the hypotonic solution, water, is less efficient. The isotonic solution (NaCl 0.9%) is a little bit better than water but the use of an hypertonic solution (NaCl 2.34%) improves the quality of the rinsing. With the same osmotic pressure, the decontamination with Diphotérine ® is quicker thanks to its amphoteric properties. Introduction Materials and methods References Conclusion Results Stirred bars Magnetic stirrer Boy Rinsing solution Flow of 150 ml/min Magnetic stirrings Internal pH pppHmetepelectr 50 ml NaOH 1N membrane semi-permeable 25ml NaCl 0.9% Evacuation tube External pH electrode Rinsing solution Flow :150ml/min Fig. 1 : Simulation of an external rinsing Fig. 2 : Simulation of a complete rinsing In vivo experiment Results : An inflexion of the pH was observed for Diphotérine ® rinsing as compared to the in vitro experiments described above. No stromal oedema was observed for Diphotérine ® rinsing but it was observed for saline solution. Fig. 7: Pathological anatomy of the cornea with a saline solution rinsing, 3 minutes after the burn with ammonia 15.3% Dosage of 1ml de NaOH 1N & 1 ml HCL 1N by different rinsing solutions 0 2 4 6 8 10 12 14 0 10 20 30 40 50 60 Volume (ml) Diphotérine ® Diphotérine ® Water Water NaCl 0.9% NaCl 0.9% physiological pH area pH External rinsing of 1 ml NaOH (1N) : comparison between Diphotérine ® , Water and Saline Solution (NaCl 0,9%) 7 8 9 10 11 12 13 14 0 20 40 60 80 Time (s) Diphotérine ® Water NaCl 0,9% Physiological pH External rinsing of 1 ml HCl 1N : comparison between Diphotérine ® , Water and Saline Solution (NaCl 0,9%) -1 0 1 2 3 4 5 6 7 8 0 20 40 60 80 100 Time (s) Diphotérine ® Water NaCl 0,9% physiological pH pH pH lavage of 50 ml soda 1N / 25 ml NaCl 0.9% with a flow of 150ml/min by : 8 9 10 11 12 13 14 0 60 120 180 240 300 360 time (min) pH Water 3 min NaCl 0.9% 3min NaCl 2.34% 3min diphotérine ® 3min Physiological pH Internal pH of the compartment

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Interest of an active rinsing solution for the decontamination of ocular corrosive splashes

Presented at Eurotox 2002, Budapest, Hungary, 15-18 Sept 2002

L. Mathieu(1), M. Gérard(2), N. Schrage(3), S. Langefeld(4), J. Blomet(1)(1) PREVOR Laboratory, Valmondois, France (http://www.prevor.com); (2) Hospital of Cayenne, Guyana, France;

(3) Augenklinik, Aachen, Germany; (4) Brüderkrankenhaus, Trier, Germany.

Severe eye burns occur rarely, but are related to a poor prognostic in rehabilitation. An emergency treatment has been identified as a decisive factor for decreasing burns (1), in vitro and in vivo experiments have been performed to show the interest of the use of an emergency active rinsing solution, as Diphotérine® (2), in comparisonwith water and saline solution.

The in vitro studies are performed to show the mechanical effect of a rinsing solution, the influence of its hypertonicity (3) and its efficacy of decreasing the aggressiveness of common corrosives. Among the vitro studies described, the first step is to evaluate the efficacy of the rinsing solution on the aggressiveness of a chemical product by a simple dosage of 1 milliliter of a corrosive, sodium hydroxide or hydrochloric acid by an increasing volume of the rinsing solution, Diphotérine versus water. A model of semi-permeable membrane was used to simulate both external and complete rinsing of the eye and cells culture were used to show the influence of hypertonicity on the diffusion and the necrotic effects of corrosives. The following carrying up represents the experiment of the simulation of the external rinsing (Fig. 1) where the pH value is measured each two seconds and the simulation of a complete rinsing (Fig. 2). In this experiment 50 milliliters of sodium hydroxide 1N and 25 milliliters of saline solution (NaCl 0.9%) are put in contact through a semi-permeable membrane. The sodium hydroxide is the chemical aggressor and the saline solution represents an internal physiologicalcompartment.

An experimental study (4) on New Zealand albino rabbits was conducted to analyse the delay for ocular rinsing in the treatment of severe ocular burns due to ammonia 15.3%. Two solutions of ocular wash, saline solution and Diphotérine®were compared.

The in vitro and in vivo experiments showed the importance of using an active rinsing solution such as Diphotérine® (5). It allowed a quick return to a physiological pH, stopping both the penetration and the aggressiveness of the corrosive. No oedema was observed when a rinsing with Diphotérine® was used for the decontamination of the ammonia burn and it was observed in the case of saline rinsing solution.

(1) Kuckelkorn R, Schrage NF, Keller G et al. Acta Ophthalmologica Scandinavica, 2002, 80, 1, 4-10(2) Kompa S, Schareck B, Tympner J, Wüstemeyer H, Schrage NF. Graefe's Arch Clin Exp Ophthalmol 2002, 240, 308-313(3) Josset-P, Meyer-MC, Blomet-J, SMT, 1986, 25-33(4) Gérard-M, Louis-V, Josset-P, Menerath-JM, Blomet-J, Merle-H J. Fr. Opht 2000, 23, 1-10(5) Hall AH, Blomet J, Mathieu L. Vet Human Toxicol 2002, 44, 4, 228-231

In vitro experiments1. COMPARATIVE DOSAGE OF CORROSIVES

2. SIMULATION OF AN EXTERNAL RINSING

Results : Only a small volume of Diphotérine® is needed to return to a physiological pH value where no chemical burn can appear. With the water or saline rinsing, there is no effect onthe corrosivity of the chemical product.

Results : For both acid (Fig.: 4) and base (Fig.: 5) rinsing, it takes less than 20 seconds to return to a physiological pH value with Diphotérine®, and about 50-60 seconds to reach the samephysiological pH value with a water or saline rinsing.

3. SIMULATION OF A COMPLETE RINSING

Results : This experiment (Fig.: 6) shows the effects of the osmotic pressure and absorption properties of the rinsing solution. The results show that the hypotonic solution, water, is less efficient. The isotonic solution (NaCl 0.9%) is a little bit better than water but the use of an hypertonic solution (NaCl 2.34%) improves the quality of the rinsing. With the same osmotic pressure, the decontamination with Diphotérine® isquicker thanks to its amphoteric properties.

Introduction

Materials and methods

References

Conclusion

Results

Stirred bars

Magnetic stirrer

Boy

Rinsing solutionFlow of 150 ml/min

Magneticstirrings

Internal pHpppHmetepelectrode

50 ml NaOH 1N

membranesemi-permeable

25ml NaCl 0.9%

Evacuation tube

External pHelectrode

Rinsing solutionFlow :150ml/min

Fig. 1 : Simulation of an external rinsing Fig. 2 : Simulation of a complete rinsingIn vivo experiment

Results : An inflexion of the pH was observed for Diphotérine® rinsing as compared to the in vitro experiments described above. No stromal oedema was observed for Diphotérine® rinsing but it was observed for saline solution.

Fig. 7: Pathological anatomy of the cornea with a saline solution rinsing, 3 minutes after the burn with ammonia 15.3%

Dosage of 1ml de NaOH 1N & 1 ml HCL 1N by different rinsing solutions

0

2

4

6

8

10

12

14

0 10 20 30 40 50 60

Volume (ml)

Diphotérine®Diphotérine®WaterWaterNaCl 0.9%NaCl 0.9%

physiological pH areapH

External rinsing of 1 ml NaOH (1N) :comparison between Diphotérine®, Water and

Saline Solution (NaCl 0,9%)

789

1011121314

0 20 40 60 80

Time (s)

Diphotérine ®

WaterNaCl 0,9%Physiological pH

External rinsing of 1 ml HCl 1N :comparison between Diphotérine®, Water

and Saline Solution (NaCl 0,9%)

-1012345678

0 20 40 60 80 100

Time (s)

Diphotérine®

WaterNaCl 0,9%physiological pH

pH pH

lavage of 50 ml soda 1N / 25 ml NaCl 0.9% with a flow of 150ml/min by :

8

9

10

11

12

13

14

0 60 120 180 240 300 360time (min)

pH

Water 3 minNaCl 0.9% 3minNaCl 2.34% 3mindiphotérine® 3minPhysiological pH

Internal pH of the compartment