evaluation of decontamination solutions

September 2006, ACS, San Francisco, CA,USA slide 1 PREVOR PREVOR LaboratoryLaboratory

Evaluation of comparative data on eye/skinchemical splash decontamination solutions:

effects on burn severity and healing

Laurence Mathieu, PhD.

Scientific Manager


Health and care– Active washing solutions for chemical splashes,

– Improvement of care for burnt victims

Environment – Active absorbent for chemical spills

Edition– “Chemical risk and occupational health”

– “Solvents”

– “MSDS” (AFNOR ed.)

Training sessions

Our job: Our job: ChemicalChemical Risk Risk “Prevent and save”


OutlineOutline of the presentationof the presentation

The chemical burn

- What is Diphoterine®?- Mechanism- Innocuousness

- Management of chemical splashes in industries- Clinical data in industries

- Experimental proofs- In vitro data- Ex vivo / In vivo data

- Management of chemical burns- Clinical study of ocular burns in Martinique- Case report of a severe ocular burn- Case report due to an acid cutaneous splash


Which chemicals produce chemical burns?

Corrosives and irritants:– acids, bases, oxidizers, reducing agents,

solvents

– or in other words, about 25 000 chemicals

It is important to note: a corrosive or an irritant can be toxic as well as noxious !



The chemical burn






What is Diphoterine®?

An aqueous solution containing the fundamental properties of water washing of all the chemical families

the effect of pulling the chemical aggressor away from the surface of the tissues

An amphoteric solutionacts on acids as well as bases, and rapidly restores the eye

and/or skin’s physiological pH

A hypertonic solutionstops the penetration of corrosive chemicals into the tissues

creating a flux from the inside to the outside of the tissues


Mechanism

Diphoterine® is a multisite molecule


Mathieu L. Accepted for publication in J Toxicol -- Cutaneous and Ocular Toxicology

- Medical device: Europe, Canada, Australia, Brazil


Mathieu L. Accepted for publication in J Toxicol -- Cutaneous and Ocular Toxicology



The chemical burn






Clinical results : Case reportsyear Number

of cases Firm / country Exposure Body surface

1999 1 Knoll AG Germany 96% sulfuric acid cheek

1998 1 Giesecke&Debrient Germany

100% nitric acid hand

1995 1 Metaleurop Germany

96% sulfuric acid Face + neck

1993 1 Mewa Germany 50% soda Forearm

1991 1 Alusuisse France Soda flakes* Left eye

1991 2 Orgachim France 98% sulfuric acid Face + neck + shoulders,

(idem + legs)

Immediate decontamination with Diphoterine®, no burn appeared, no sequelae, no need of secondary care, no loss of work


INRS

(French National Institute of Research and Safety)

Falcy M et al. DMT, 53, 1993, 33-41 and DMT, 70, 1997

Comparative Comparative studystudy betweenbetweenDiphoterineDiphoterine®® andand waterwaterwashingwashing in 73 in 73 firmsfirms about about 145 145 chemicalchemical splashessplashes

REDUCED THE REDUCED THE SERIOUSNESS OF SERIOUSNESS OF THE ACCIDENTSTHE ACCIDENTS

STOPPED THE PAINSTOPPED THE PAIN

Clinical results : comparative study


Clinical results of 42 cases of chemical splashesMartinswerk, Germany, 1991-1993

washing Diphoterine® acetic acid waterSick leave 0.18d ±0.4 2.91d ± 4.3 8d ± 8.12No care 100% ±15 0% ±15 0% ±15Basic care 0% ±15 80% ±15 25% ± 15Medical care 0% ± 15 20% ± 15 75% ± 15

Chemical product: soda (40-600 g/l)Protocol: On site washing

Results: Variability of the effectiveness of water washing Significant improvement with Diphoterine® washing

Hall AH et al. Vet Hum Toxicology 2002, 44, 4, 228-231


Study on 375 cases at ATOFINA, France, 2000

Chemicals: Acrylates, sulfuric acid (98%), Oleum, soda (22%), Diethylaminoacrylate (ADAME)

Results: Significant difference in sick leave, as well as in the necessity of secondary care

washing water Diphoterine pSick leave 7 (3.4%) 0 (0%) < 0.05Without sick leave 198 170Without follow-up* 68(52%) 88(33%) <0.05With follow-up 137 82*The criterion without follow-up corresponds to no care

Hall AH et al. Vet Hum Toxicology 2002, 44, 4, 228-231



The chemical burn






Diphoterine®: In vitro effectsby simple dosage of corrosives

Dosage of 1ml of normal soda & 1 ml of normal HCL by Diphotérine versus water

0

2

4

6

8

10

12

14

0 10 20 30 40 50 60Volume (ml)

pH

physiological pH area

water

Diphoterine

Diphoterine

water

Mathieu L et al Toxicology Letters 2002, supplement 1/135, 290, S148


Magneticstirrings

Internal pH

50 ml of corrosiveproduct

semi-permeablemembrane

25mlNaCl 0.9%

Evacuation tube

External pH

washing solutionFlow :150ml/min

Simulation of a complete washingDiphoterine®: In vitro effects

Mathieu L et al Toxicology Letters 2002, supplement 1/135, 290, S148


Diphoterine®: In vitro effects

Simulation of a complete washing

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

8

9

10

11

12

13

14

0 60 120 180 240 300 360

time (min)

pH

eau 3 minNaCl 0.9% 3minNaCl 2.34% 3mindipho 3minpH physio

Internal pH of the compartment

graphe 4

water 3 min0.9% NaCl 3 min2.34% NaCl 3 minDiphoterine 3 minphysiological pH

Josset P, Meyer MC, Blomet J.SMT 1986, 85, 25-33

Influence of osmolarityInfluence of amphoter



The chemical burn





Diphotérine®

No rinsing

Saline solution

pH

0

-1

0.5

1

1.5

2

2.5

3

- 0.5

0.05 0.4

1.15

2.25 3

3.35 4.

1

4.45 5.

2

5.55 6.3

7.05 7.

4

8.15 8.

5

9.25 10

10.3

5

11.1

Time (mn)

PCA = 36.8

PCA = 15.9

PCA = 20.3

In vivo comparative studySaline solution versus Diphoterine®

18 rabbit eyespHmeter probe in the anterior chamber0.01 ml of 15.3 % ammonia during 1 min of contactpH measurements every 5 seconds250 ml of saline solution versus Diphotérine®

Histology of the cornea

Gérard M, Josset P, Louis V, Ménérath JM, Blomet J, Merle H. Existe-il un délai pour le lavage oculaire externe dans le traitement d’une brûlure oculaire par l’ammoniaque ? Comparaison de deux solutions de lavage : sérum physiologique et Diphotérine*. J Fr Ophtalmol 2000 ; 5 : 449-458.

Diphotérine®: inflexion of pH curve = decrease of pH


Cornea burnt by ammonia

washing after 3 min of contact

By saline solution:

- Coagulated epithelium,

- edematous stroma

By Diphotérine® :

- Vacuolisated and coagulatedepithelium,

- Normal stroma


Experimental in vivo,prospective, randomized, blind

study of a cutaneous burn due to concentrated hydrochloric acid

Cavallini M, Casati A. European Journal ofAnaesthesiology 2004, 21, 389-392

Cavallini M, de Broccard F, Corsi MM, Fassati LR,Baruffaldi Preis FW. Annals of burns and fire disasters 2004, XVII, 2, 1-5


Skin study in rats (concentrated HCl burn)

Saline solution versus Diphoterine®

Significant statistical results in favour of Diphoterine®

Decrease of inflammation (IL-6 à 48h, p < 0.01; à 7 days, p < 0.05)

Decrease in pain(substance P within 48h, p < 0.05; β-endorphin at 7 days, p<0.05)

Decrease in the size of the lesions(no washing : 12mm; saline solution : 6 mm; Diphoterine 4 mm)

Improvement of the scarring



The chemical burn






Prospective studyon ocular chemical burns in Martinique

Merle H, Donnio A, Ayeboua L, Michel F, Thomas T,F, Ketterle J, Leonard C, JossetP, Gerard M. Alkali ocular burns in Martinique (French West Indies) Evaluation of the use of an amphoteric solution as the washing product. Burns 2005, 31, 205-211


Clinical study in Martinique Comparison saline solution / Diphoterine®

Delayed ocular washing

Teams (300 people) : fire-fighters, Emergency Medical Assistance Service(SAMU), Hospital Emergency Rooms, Ophthalmology

Number of patients : 66 during 4 years (before/after study)

48 eyes (46%) saline solution / 56(54%) Diphoterine®

Protocol : washing with saline solution or Diphoterine® then the same treatment according to the grade of the burn

Chemicals : bases (48% with Alkali, ammonia 15.3%)

Nature of the splash : attack

victim : male (2 patients out of 3)


Clinical study in Martinique Comparison saline solution / Diphoterine®

Delayed ocular washing

Length of time (days) Saline Diphoterine® preepithelialisation solution

grade 1 11.1±1.4 1.9 ±1 10-7

grade 2 10 ±9.2 5.6 ±4.9 0.02

grade 3 45.2 ±23 20 ±14.1 0.21 NS

Results :

significant difference for grades 1 and 2,tendency for grade 3, no grade 4 in the group Diphoterine®

A case report of a severe Grade 4 burn before the beginning of the clinical study

Woman, 49 years old, assaulted at work place

Grade 4 right eye

Visual acuity < 1/10

Limbic ischemia on 360°

Scleral necrosis

Diphotérine® : 1 hour after the splash

Decrease of stromal edema (AV 0.3)

Application of an adapted treatment

Gérard M, Merle H, Chiambaretta F, Rigal D, Schrage N. An amphoteric rinse used in the emergency treatmentof a serious ocular burn. Burns, 2002, 28, 670-673


Ocular Grade 4Gérard et al, Burns 2002, 28, 670-673

Healing after 180 days

without grafting



The chemical burn






A case report of a cutaneous acid splashJuly 28 2005

What happened?Mr B, tube worker, was victim of a chemical burn on his face, neck andright ear, due to a large amount of 98% sulfuric acid, while opening a badly purged pipe.

Details of decontaminationDecontamination with water was delayed (around 5 min) and induceda 3rd degree burn. Decontamination with Diphoterine® started 15 min after with the arrival of the company nurse at workstation.

Dr Bérengère BELLIARD, MD


The use of Diphoterine®, beyond an immediate analgesic effect, allows an important decrease of the seriousness of the burn

Diphotérine Stops the action of the chemical product.

The employee was sent to a hospital emergency room.

4 hours after the accident, the company doctor in accordance with the emergency room doctor, decided to continue the washing with Diphoterine® for 24 hours, because of the severity of the lesions and the foreseeable action of Diphoterine®.

The washing was be followed up 48 hours later at the employee’s request.

Evolution of the lesions


24 h after the accident,some 3rd degree burn areas,

large edema.

Evolution of the lesions

72 h after the accident,No edematous grade,

exsudative auditory duct.No more visible 3rd degree lesions

The employee worked at an adapted workstation in a clean area during the entire medical treatment.

29 days after the accident,wound healing was almost

complete.


Effects on burn severity and healing• Decrease the length of contact with the chemical product

⇒ wash as soon as possible

• Accelerate and optimize the decontamination process- from the polyvalent and mechanical properties of washing with water

⇒ external decontamination of tissues- to an active solution with additional chemical and physical properties

⇒ internal decontamination of tissues

• When the burn has already appeared

- apply an adapted treatment to decrease ⇒ inflammation, pain and secondary infection

evaluation of decontamination solutions

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