Chemical Trauma
Roswell R. Pfister
INTRODUCTION AND HISTORICAL BACKGROUND
Humans have encountered a variety of naturally occurring powerful chemicals from the dawn of civilization. As industry evolved, so did the requirement for a greater variety and strength of chemicals to meet the needs of developing civilizations. Chemical injuries of the eye have had poor outcomes, particularly since the age of the industrial revolution, when large numbers of workers first became exposed to a wide variety of powerful chemicals in the production of manufactured items from raw materials. It was natural for physicians to employ mechanistic, animal, or vegetable therapies to what seemed to be an inevitable conclusion: pain, blindness, and often, loss of the eye. Until relatively recently this outcome was still common. Progress has been made toward delineating the nature of the destructive inflammatory process and the subsequent repair of many tissues crucial to ocular stability. In many cases there is now the realistic prospect of return of considerable vision, following chemical trauma.
EPIDEMIOLOGY
Injury by a chemical occurs in the workplace, in the home or its environs, or as a direct result of an assault. In the past the concept of safety for workers was not a consideration taken seriously, nor were there any safety engineers to guard against accidental injuries. In many parts of the world this unsafe situation still exists.
There are profound psychological, social, and economic repercussions that occur after chemical injury. Injury of one eye often results in costly medical care dependency, loss of job, interpersonal conflicts, and isolation for the period of time necessary to stabilize the injured eye. Blindness resulting from bilateral injury severely restricts job and economic opportunities, with an additional burden placed on the family and social systems for subsidence and loss of taxable income.
Chemical injury can be acidic, alkaline, or toxic. Strong acids causing injury include sulfuric, hydrochloric, nitric, and hydrofluoric. Alkalis causing eye injury include ammonium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, and calcium hydroxide (1). Toxic agents include a huge variety of chemicals that are destructive to biologic tissues, but that are not particularly acidic or alkaline. Table 43-1 summarizes the sources and relevant comments pertaining to the commonest types of acid and alkali injury. In addition, a comprehensive review of chemical injuries is presented by Wagoner (2).
Data gathered from a large urban hospital show that young black men are at greatest risk of a severe alkali-injury assault, usually in a domestic setting, where there is low income, high-density housing, and a record of alcoholism and prior assaults (3). In the industrial sector, approximately 10% of 52,142 cases of ocular trauma reported from 16 states were chemical injuries (1.6% acid and 0.6% alkali). Safety monitors have reduced the incidence of job-related eye injuries, but despite such programs, the storage and use of powerful chemicals, under extreme pressure and high temperature, continue to pose serious threats even to the properly attired worker wearing protective clothing and goggles.
Of 221 chemical injuries reported in 180 patients at the Croyden Eye Unit, United Kingdom, there were nearly twice as many alkali as acid injuries. Males comprised 75.6% and females 24.4% of all injuries. Most patients were between the ages of 16 and 25 (4). Accidental injuries accounted for 89.4%, and the remainder assaults. Work-related accidents accounted for 63%, and 33% occurred at home and 3% at school.
Two large series of chemical injuries were reported by Kuckelkorn et al. (5) in Aachen, Germany, in 1990 to 1991. In the first report 236 injuries occurred in 171 patients of whom 70% were males. Industrial accidents accounted for 61%, 37% were household accidents, and 2% unknown. Most injuries were classified as mild (88%). In Kuckelkorn et al. (6) second series, they evaluated 42 patients sustaining severe alkali injuries occurring over a 7-year period. The industrial sector contributed 73.8%, and the rest were sustained at home.
Farmers using liquid ammonia as fertilizer in remote areas, and homeowners using powerful cleansing agents, without eye protection, continue to be at special risk.
TABLE 43-1. CHEMICALS COMMONLY USED IN INDUSTRY OR IN THE HOME | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Last, the deployment of certain types of automobile airbags occasionally releases sodium hydroxide as part of the chemically driven, rapid inflation process, causing corneal abrasions and mild alkali injuries. Although these cases make up 21.6% of eye injury cases caused by airbags, in most cases they heal readily (7).
MAJOR CHEMICAL DIFFERENCES AMONG ALKALI, ACID, AND TOXIC INJURY OF THE EYE
Alkali
The pain, lacrimation, and blepharospasm following an ocular alkali injury result from direct injury of free nerve endings located in the epithelium of the cornea, conjunctiva, and eyelids. Depending on the severity of the injury, a wave of hydroxyl ions rapidly advance through ocular tissues causing saponification of cellular membranes with massive cell death and extensive hydrolysis of the corneal matrix consisting of glycosaminoglycans and collagen.
Ammonia
Ammonia (NH3) is encountered as a fertilizer and a refrigerant as well as in the manufacturing of other chemicals. The most common form is household ammonia, a 7% solution used as a cleaning agent. Ammonia fumes stimulate the eye to secrete tears, which tends to dilute the chemical, reducing its potential for major ocular damage. However, the gas is soluble in water and tears. With prolonged exposure to the eye, ammonia gas forms ammonium hydroxide (NH4OH), capable of causing major ocular damage. The lipid solubility and high penetrability of ammonia allow it
to pass through the cornea and into the eye almost instantaneously (8). Such rapid penetration makes the injury very difficult to ameliorate by subsequent irrigation.
to pass through the cornea and into the eye almost instantaneously (8). Such rapid penetration makes the injury very difficult to ameliorate by subsequent irrigation.
Lye
Lye [i.e., sodium hydroxide (NaOH), caustic soda, sodium hydrate] penetrates into the interior of the eye in 3 to 5 minutes (8). Solid sodium hydroxide, often used as a drain cleaner, can cause pressure to develop within the drain pipe, with resultant explosion of lye into the face and eyes of the unprepared. Warmed lye is also commonly used to straighten kinky hair. Lye injuries rank second in severity to those produced by ammonium hydroxide.
Other Hydroxides
Potassium hydroxide (KOH, caustic potash) and magnesium hydroxide [MG(OH)2] are less usual causes of chemical injuries of the eye. Potassium hydroxide penetrates the eye slightly less rapidly than sodium hydroxide but the injuries are of similar severity. Magnesium hydroxide is found in sparklers and flares; the combination of thermal injury and chemical injury accounts for more severe injury than that occurring as a result of heat alone (9).
Lime
Injuries from lime [Ca(OH)2], fresh lime, quicklime [CaO + H2O = Ca(OH)2], calcium hydrate, slaked lime, hydrated lime, plaster, mortar, cement, and whitewash, used primarily in the building industry, are common sources of ocular injuries. It penetrates the eye less rapidly because it reacts with epithelial cell membranes, forming calcium soaps that precipitate and hinder further penetration. Despite that, these injuries can be quite severe with the corneal opacity visible before the opacities seen as a result of ammonium or sodium hydroxide (10).
 FIGURE 43-1. A: Acid injury of the cornea and adjacent conjunctiva. Note the opalescent surface, a consequence of protein denaturation of the full thickness of the affected epithelium. B: Stripping off the cloudy epithelial layer uncovers the underlying crystal clear corneal stroma. Healing can take place without scarring or with very mild superficial nebulae.(see color image) |
Methyl Ethyl Ketone Peroxide
Methyl ethyl ketone peroxide is a catalyst commonly used in various industries. Immediate and delayed corneal injury can occur. Exacerbations and remissions of limbal and corneal disease lasting more than 20 years have been reported (11).
Acid
Weak acidic compounds contacting the outer eye precipitate proteins within the corneal and conjunctival epithelium, thus acting as a partial barrier to further ingress of the chemical. In their wake is left a grayish-white epithelium, often obscuring all tissues posterior to it. Stripping off this opacified epithelial layer often reveals a relatively clear underlying corneal stroma (Fig. 43-1). As long as the corneal stem cells ringing the cornea are not damaged, then epithelial recovery is likely with little or no stromal cloudiness.
Very strong acids, however, overcome this precipitated proteinaceous obstacle handily and progress through tissue much as alkali. The end result of a very severe acid injury is often indistinguishable from that of an alkaline injury. For that reason this chapter deals with alkaline and acid injuries as one entity, unless otherwise specified.
Sulfuric Acid
Sulfuric acid (H2SO4) is a commonly used industrial chemical as well as the acid used in batteries. The great
avidity of concentrated sulfuric acid for water results in the release of heat, the cause of tissue charring. Sulfuric acid produces injuries ranging from mild to very severe. Most of the injuries, especially the more severe ones, occur as the result of battery explosions. Hydrogen and oxygen are produced by electrolysis when sulfuric acid combines with water in the battery. This gaseous mixture explodes on contact with flame. Matches or cigarette lighters used as illumination sources or sparks produced by jumper cables are the most common modes of ignition. Injuries that result from battery explosions commonly are combinations of acid burn and contusion from particulate matter but might also show laceration or intraocular foreign body penetration.
avidity of concentrated sulfuric acid for water results in the release of heat, the cause of tissue charring. Sulfuric acid produces injuries ranging from mild to very severe. Most of the injuries, especially the more severe ones, occur as the result of battery explosions. Hydrogen and oxygen are produced by electrolysis when sulfuric acid combines with water in the battery. This gaseous mixture explodes on contact with flame. Matches or cigarette lighters used as illumination sources or sparks produced by jumper cables are the most common modes of ignition. Injuries that result from battery explosions commonly are combinations of acid burn and contusion from particulate matter but might also show laceration or intraocular foreign body penetration.
Sulfurous Acid
Sulfur dioxide (SO2) forms sulfurous acid (H2SO3) when it combines with water in ocular tissue. It might be encountered as sulfurous anhydride or sulfurous oxide, a fruit and vegetable preservative, bleach, and refrigerant. When used as a refrigerant, it is mixed with oil. Tissue injury is more severe in patients damaged from SO2 mixed with oil because the hydrocarbon prolongs contact. Ocular and tissue damage are severe when a direct jet of the gas or liquid and oil hits the skin or eye. The initial injury damages the corneal nerves, resulting in relative tissue anesthesia and little discomfort. At first, visual acuity is not severely affected but it worsens greatly over hours to days as the ocular condition deteriorates. It is not the sulfur dioxide’s freezing effect on the tissue that produces the injury but rather sulfurous acid itself, denaturing protein, and inactivating numerous enzymes. Because of its high lipid and water solubility, sulfurous acid penetrates the tissues easily.
Hydrofluoric Acid
Hydrofluoric acid (HF, hydrogen fluoride) is a weak inorganic acid but a strong solvent. It has been used for centuries, but in current industry use it is found either in its pure form (in solutions ranging from 0.5% to 70.0% in strength) or mixed with other agents such as nitric acid, ammonium difluoride, and acetic acid. Hydrofluoric acid is used in etching and polishing glass and silicone and in frosting glass. It is also used in the pickling or chemical milling of metals, as well as in the refining of uranium, tantalum, and beryllium. It is also used in the alkylation of high-octane gasoline, the production of elemental and inorganic fluoride, and the preparation of organic fluorocarbons. It has found a new use in the semiconductor industry where it is essential technology in the manufacture of silicon chips for computers and other devices controlled by digital technology. It is so highly toxic that as little as 7 mL or a 2.5% burn of the body is sufficient to cause death from uncontrolled hypocalcemia (12).
Much has been written on skin burns caused by hydrofluoric acid; however, the literature is sparse relative to that for ocular injuries. Hydrofluoric acid produces a severe ocular injury because of its high degree of activity in dissolving cellular membranes. In addition, the low molecular weight and small size of the hydrofluoric acid molecule allow it to penetrate the tissues readily.
Other Acids
Chromic acid is a strong caustic derived from chromic oxide and chromium trioxide (Cr2O3). Rare cases of severe ocular injury have occurred after direct instillation of the liquid in the eye. However, ocular injuries caused by chromic acid are more often associated with exposure to droplets of the acid in the chrome-plating industry, resulting in chronic conjunctival inflammation and a brown discoloration of the epithelium in the interpalpebral fissure.
Hydrochloric acid is commonly used as a 32% to 38% solution. Hydrogen chloride gas is irritating to the eye; thus, the profuse tearing serves to limit ocular damage.
At high concentrations and with prolonged exposure, liquid hydrochloric acid produces severe ocular damage.
Injuries produced by nitric acid (HNO3) are similar to those produced by hydrochloric acid, except that the epithelial opacity produced by nitric acid is yellowish rather than white as it is in the other acid burns.
Acetic acid (CH3COOH), a relatively weak organic acid, is also known as ethanoic acid, ethylic acid, methane carboxylic acid, vinegar acid, and glacial acetic acid. The various forms of acetic acid, especially vinegar acid (4% to 10% acetic acid) typically produce only minor ocular damage, unless exposure is prolonged. Exposure to a solution greater than 10% produces a severe injury unless the time of exposure is exceedingly short. “Essence of vinegar” (80% acetic acid) and glacial acetic acid (90%) are the most concentrated forms of acetic acid likely to produce severe ocular injury.
Toxic
Other types of chemical injuries of the eye are usually less severe than alkali and acid injuries. The reader is referred to Grant’s (13) Toxicology of the Eye for a detailed discussion of the adverse ocular effects of petroleum products and other organic chemicals.
Chemical mace and similar compounds can cause minor to severe ocular injury, depending on a number of factors. These tear gas compounds are not under government regulatory control; hence considerable variability exists in commercially available products. Ocular injury associated with the original chemical mace is caused by the lacrimator chloroacetophenone. When possible, the exact product formulation should be obtained to determine if other toxic substances have been added. The degree of
severity of reported injuries is related to proximity of the spray can to the eye, quantity of chemical entering the eye, duration of exposure, state of normal reflex mechanisms, and the mechanism of propelling the chemical, for example, solvent spray, pressurization, or explosion.
severity of reported injuries is related to proximity of the spray can to the eye, quantity of chemical entering the eye, duration of exposure, state of normal reflex mechanisms, and the mechanism of propelling the chemical, for example, solvent spray, pressurization, or explosion.
Police recommend directing the spray away from the eyes or at the eyes of unconscious individuals, and from a distance greater than 6 feet. Under these conditions only minor injury is likely to occur (13). If a larger quantity of the chemical is applied directly to the surface of the eye, especially in the absence of normal reflexes, severe injury may occur. Loss of ocular surface epithelium, severe persistent stromal edema, presumably secondary to endothelial damage, stromal clouding, and corneal neovascularization are among the resultant injuries.
The reader is referred to a comprehensive review of mustard gas injuries inflicted during military campaigns (14).
THE NATURAL SEQUENTIAL COURSE OF CHEMICAL INJURIES
Strong chemicals exert their destructive effect directly by damaging cellular and extracellular matrices and indirectly by initiating an inflammatory process that is not necessarily time-limited.
Some alkali can penetrate into the anterior chamber in 5 to 15 seconds, reaching a maximum in 2 to 3 minutes. The poor buffering capacity of anterior segment tissues and aqueous humor is rapidly overcome. There is a sudden, spiking rise in the intraocular pressure up to 20 to 40 mm Hg above normal lasting about 10 minutes, caused primarily by shrinkage of the collagenous envelope of the eye. A more prolonged rise in pressure quickly follows, secondary to prostaglandin release (15). Within 1 minute, the severe rise in aqueous humor pH causes lysis of corneal cells as well as those lining and adjacent to the anterior chamber, compromising the blood-aqueous barrier and releasing necrotic debris into the aqueous humor. This leads to a severe fibrinous inflammatory reaction in the entire anterior segment of the eye.
Glaucoma may ensue from inflammatory products accumulating in the aqueous humor and chamber angle, promoting closure by anterior synechiae, especially inferiorly. The travecular meshwork and ciliary body may be injured directly by penetration of alkali through the sclera or by contact with alkalotic aqueous humor percolating through the meshwork. Ocular hypertension or hypotension, or both, may occur at different time periods, depending on the predominance of one or more factors. Chemical injury to the iris, crystalline lens, and ciliary body may produce mydriasis, cataract, and even phthisis bulbi, respectively. Externally, this inflammatory reaction may be so profound as to lead to extensive symblephara and even ankyloblepharon from the apposition of raw conjunctival folds and the inexorable scarring process, severely contracting the total conjunctival surface area.
REPAIR PROCESSES
Self-repair of the eye after a severe chemical injury is a complex process that involves both cellular and extracellular components of each tissue layer, including the eyelids, corneal and conjunctival epithelium, fibroblasts, collagen and glycosaminoglycans, endothelium, and all other tissues contiguous to the anterior chamber. The repair of each tissue is interdependent on other tissues, both contiguous and non-contiguous.
Epithelium
Destruction of the corneal epithelium alone in a mild injury might lead, at most, to a recurrent corneal erosion, resulting from injury to the basal lamina and anterior corneal stroma. When a portion of the limbal stem cells is destroyed, the remaining stem cell population heals first by the propagation of pluripotential epithelial stem cells around the corneal periphery and then by centripetal growth of transitional and daughter cells phenotypic for cornea. If the injury destroys the full thickness of the limbal palisades of Vogt, then the phenotypic source of corneal epithelium is lost. Under these circumstances, resurfacing the cornea requires that the remaining conjunctival epithelial cells must first spread over the collagenous tissues of Tenon’s capsule or the subjacent episclera and then continue over corneal stroma. On the cornea, this rate of spread is initially similar to epithelial recovery occurring after a simple abrasion (16,17).
When the injury to the cornea is very severe, but the corneal epithelial stem cell population is left intact, then initial epithelial healing still usually proceeds at a rate similar to that when the stem cell population has been destroyed (16). An experimental alkali-injury of 12 mm, which did not destroy the limbal stem cells, showed substantial epithelial adhesion problems leading to persistent epithelial defects. At 84 hours, epithelial movement usually stops when the leading edge loses its adherence and then subsequently peels back from the stroma as a sheet (96 hours), thereafter maintaining a persistent epithelial defect. It has been suggested that this loss of epithelial adhesion might result from accelerated degradation of fibrinogen by plasminogen activator, a substance probably secreted in excessive amounts by the basal epithelial cells in the alkali-injured eye (18). Therefore, in the alkali-injured cornea, the presence of a normal corneal stem cell population does not necessarily imply that epithelial healing is assured. In fact, persistent epithelial defects might result from the consequences of a denatured framework of the stroma. Clearly, epithelial-stromal
interaction plays an important role in the adhesion of epithelium to stroma.
interaction plays an important role in the adhesion of epithelium to stroma.
