MONOGRAPH FOR UKPID LYE Nicky Bates National Poisons Information Service (London Centre) Medical Toxicology Unit Guy's & St Thomas' Hospital Trust Avonley Road London SE14 5ER UK This monograph has been produced by staff of a National Poisons Information Service Centre in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Peer review group: Directors of the UK National Poisons Information Service. 1 SUBSTANCE/PRODUCT NAME 1.1 Origin of substance Made by reacting calcium hydroxide with sodium carbonate, from sodium chloride electrolysis and from sodium metal and water vapour at low temperature. 1.2 Name 1.2.1 Brand/trade name 1.2.2 Generic name 1.2.3 Synonyms Sodium hydroxide, lye (sodium hydroxide solution, but may also refer to potassium hydroxide solution), caustic soda, sodium hydrate, white caustic, caustic flake, natriumhydroxide (German), natriumhydroxyde (Dutch). 1.2.4 Common names/street names Not applicable. 1.3 Chemical group/family Alkali. 1.4 Substance identifier and/or classification by use 1.5 Reference numbers CAS 1310-73-2 RTECS WB 4900000 EINECS 2151855 UN 1823 (dry solid) 1.6 Manufacturer No data. 1.7 Supplier/importer/agent/ licence holder Bayer Diagnostics, Bayer plc, Evans House, Hamilton Close, Basingstoke, Hants, RG21 2YE Tel: 01256 29181 Diversey Ltd, Weston Favell Centre, Northampton, NN3 8PD Tel: 01604 405311 Fax: 01604 406809 Evans Vanodine International plc, Brierley Rd, Walton Summit Centre, Preston, PR5 8AH Tel: 01772 322200 Fax: 01772 626000 Lever Brother s Ltd, 3 St James; Rd, Kingston-upon-Thames, Surrey KT1 2 BA Tel: 0181 542 8200 SC Johnson, Frimley Green, Camberley, Surrey, GU16 5AU Tel: 01276 852377 Fax: 01276 852688 SC Johnson Professional, Frimley Green, Camberley, Surrey, GU16 5AU Tel: 01276 852706 Fax: 01276 852800 1.8 Presentation 1.8.1 Form Clinitest(R): white pale blue mottled tablets. Auto Dishwash: thin yellow liquid. Auto Dishwash Extra: thin yellow liquid. Auto Glass Wash: thin yellow liquid. Beerline: thin colourless liquid. Chlorinated Dishwash: thin pale yellow liquid. Crystal: white powder. D9 Oven Cleaner: thin brown liquid. Diverforce L3: thin yellow/green liquid. Diverforce L4: thin straw coloured liquid. Diverforce L6: thin straw coloured liquid. Divocare MSD: thin red liquid. Divocare MSD Super: thin red liquid. Divocare OC: brown gel. Filter Cleaner: thin yellow liquid. Green Top Bottle Washing Detergent: pale yellow powder. HMD Plus: thin straw coloured liquid. M1: thin red liquid. Mr Muscle Drain Opener, sachet: granules. Mr Muscle Oven Cleaner: aerosol. Mr Muscle Professional Oven Cleaner: aerosol. Mr Muscle Sink and Plughole Opener: hazy, straw coloured liquid. Oven Cleaner: viscous colourless liquid. Pastueriser Cleaner Liquid: thin yellow liquid. Pastueriser Powder: white powder. SPA Plus: thin straw coloured liquid. Sun Liquid: white viscous liquid. Sun Lemon Fresh Liquid: white viscous liquid. TC Plus: thin yellow/green liquid. Unipak G1: white powder. Unipak G3: white powder. Unipak G5: white powder. Pastueriser Cleaner Liquid: thin yellow liquid. Vanosan: thin pale yellow liquid. 1.8.2 Formulation details Clinitest(R) tablets (Bayer Diagnostics): sodium hydroxide 232.5mg. Auto Dishwash (Evans Vanodine): sodium hydroxide 8.33% (pH 13.6 as supplied), 11.3 (working solution), TAR 8.71g NaOH/100g) Auto Dishwash Extra (Evans Vanodine): sodium hydroxide 8.83% (pH 13.7 as supplied), 11.6 (working solution), TAR 10g NaOH/100g) Auto Glass Wash (Evans Vanodine): sodium hydroxide 4.75% (pH 13.6 as supplied), 11.7 (working solution), TAR 5.58g NaOH/100g) Beerline (Evans Vanodine): sodium hydroxide 14.8% (pH 13.7 as supplied), 12.6 (working solution), TAR 14.8g NaOH/100g) Chlorinated Dishwash (Evans Vanodine): sodium hydroxide 10-20% (pH 13.65 as supplied), 11.8 (working solution), TAR 10.22g NaOH/100g) Crystal (Evans Vanodine): sodium hydroxide 45% (pH 13, TAR 44.1% NaOH/100g) D9 Oven Cleaner (Diversey): sodium hydroxide 10% (pH 13.9) Diverforce L3 (Diversey): sodium hydroxide 10% (pH 13 (as supplied), 11 (working solution)) Diverforce L4 (Diversey): sodium hydroxide 14% (pH 13.9 (as supplied), 11(working solution)) Diverforce L6 (Diversey): sodium hydroxide 10% (pH 13.9 (as supplied), 11(working solution)) Divocare MSD (Diversey): sodium hydroxide 14% (pH 13.9 (as supplied), 11(working solution)) Divocare MSD Super (Diversey): sodium hydroxide 14% (pH 13.9 (as supplied), 11(working solution)) Divocare OC (Diversey): sodium hydroxide 6% (pH 13.9) Filter Cleaner (Evans Vanodine): sodium hydroxide 8.33% (pH 13.6 as supplied), 11.3 (working solution), TAR 8.71g NaOH/100g) Green Top Bottle Washing Powder: (Evans Vanodine): sodium hydroxide 76%, (pH 12.5, TAR 67.85g NaOH/ 100g) HMD Plus (Diversey): sodium hydroxide 14% (pH 13 (as supplied), 11(working solution)) M1 (Diversey): sodium hydroxide 5.5% (pH 13.9 (as supplied), 11.5(working solution)) Mr Muscle Drain Opener, sachet (SC Johnson): sodium hydroxide 52% (pH 13.5) Mr Muscle Oven Cleaner (SC Johnson): sodium hydroxide 1-5% (pH 13.2) Mr Muscle Professional Oven Cleaner (SC Johnson Professional): sodium hydroxide 1-5% (pH 13.5-14) Mr Muscle Sink and Plughole Opener (SC Johnson): sodium hydroxide 1-5% (pH 13) Oven Cleaner (Evans Vanodine): sodium hydroxide 5-10% (pH 13.8, TAR 9.67g NaOH/100g) Pastueriser Cleaner Liquid (Evans Vanodine): sodium hydroxide 8.83% (pH 13.7 (as supplied), 11.6 (working solution), TAR 10g NaOH/100g) Pastueriser Powder (Evans Vanodine): sodium hydroxide 40% (pH 12.5, TAR 40.65g NaOH/100g) SPA Plus (Diversey): sodium hydroxide 10% (pH 13 (as supplied), 11(working solution)) Sun liquid (Lever): sodium hydroxide 1-5% (pH 13.6) Sun Lemon Fresh Liquid (Lever): sodium hydroxide 1-5% (pH 13.6) TC Plus (Diversey): sodium hydroxide 10% (pH 13 (as supplied), 11 (working solution)) Unipak G1 (Diversey): sodium hydroxide 57% (pH 12) Unipak G3 (Diversey): sodium hydroxide 35% (pH 12) Unipak G5 (Diversey): sodium hydroxide 20% (pH 12) Vanosan (Evans Vanodine): sodium hydroxide 10-20% (pH 13.65 (as supplied), 11.5 (working solution), TAR 10.91 NaOH/100g) 1.8.3 Pack sizes available Clinitest(R) tablets: 36 tablet pack. Auto Dishwash: 5 L and 25 L bottles. Auto Dishwash Extra: 5 L and 25 L bottles. Auto Glass Wash: 5 L and 25 L bottles. Beerline: 5 L and 25 L bottles. Chlorinated Dishwash: 25 L bottles. Crystal: 15 kg buckets. D9 Oven Cleaner: 2 L bottle. Diverforce L3: 20 L drum. Diverforce L4: 5 L, 25 L and 200 L drums. Diverforce L6: 5 L and 20 L drums. Divocare MSD: 20 L and 5L drums. Divocare MSD Super: 20 L and 5L drums. Divocare OC: 5 L drums. Green Top Washing Powder: 25 kg bucket. HMD Plus: 20 L drum. M1: 2L bottle. Mr Muscle Drain Opener, sachet: 60g. Mr Muscle Oven Cleaner: 250ml, 300ml, 450ml, 500ml. Mr Muscle Professional Oven Cleaner: 500ml. Mr Muscle Sink and Plughole Opener: 500ml. Oven Cleaner: 5 L bottles. Pastueriser Cleaner Liquid: 25 L bottles. Pastueriser Powder: 25 kg buckets. SPA Plus: 5 L and 20 L drum. Sun Liquid: 1L, 3L bottles. Sun Fresh Lemon Liquid: 1L, 3L bottles. TC Plus: 20 L drum. Unipak G1: 4.5 kg direct dispense bottles. Unipak G3: 4.5 kg direct dispense bottles. Unipak G5: 4.5 kg direct dispense bottles. Pastueriser Cleaner Liquid: 25 L bottles. Vanosan: 25 L bottles. 1.8.4 Packaging See above. 1.9 Physico-chemical properties Chemical structure NaOH, molecular weight 40.01. Physical state Fused solid with crystalline structure available as pellets, sticks, flakes or lumps. Colour White. pH Of 0.05% solution about 12, of 0.5% solution about 13 and of a 5% solution about 14. Solubility in water and organic solvents 1g of sodium hydroxide dissolves in 0.9ml water, 0.3ml boiling water, 7.2ml absolute alcohol and 4.2ml methanol. It is also soluble in glycerol. Important chemical interactions Readily absorbs carbon dioxide and water from air. Generates heat when dissolving or when mixed with an acid. Corrosive to organic tissue and to aluminium metal in the presence of moisture. Reacts violently with acetaldehyde, acetic anhydride, acrolein, acrylonitrile, allyl alcohol, allyl chloride, chlorohydrin, chloronitrotoluenes, chlorosulphonic acid, 1,2-dichloroethylene, ethylene cyanhydrin, glyoxal, hydroquinone, maleic anhydride, nitroethane, pentol, oleum, phosphorous, tetrahydrofuran, trichloroethylene, water, 4-chloro-2-2methylphenol, cinnamaldehyde, cyanogen azide, diborane, 4-methyl-2-nitrophenol, 3-methyl-2-penten-4-yn-1-ol, 1,2,4,5-tetrachlorobenzene (to form 2,3,7,8-tetrachlorobenzodioxin), 1,1,1-trichloroethanol, trichloronitromethane, zinc and zirconium. Major products of combustion/pyrolysis Sodium hydroxide is not combustible but the solid form on mixing with moisture or water may produce sufficient heat to ignite combustible material. When heated to decomposition sodium oxide (Na2O) is produced. Boiling point 1390°C 5% solution 102°C 10% solution 105°C 20% solution 110°C 30% solution 115°C 40% solution 125°C 50% solution 140°C Melting point 318.4°C Density 2.13 g/cm3 at 25°C Vapour pressure 1 mmHg at 739°C Reactivity Sodium hydroxide reacts vigorously with 1,2,4,5-tetrachlorobenzene to form 2,3,7,8-tetrachlorobenzodioxin. Mixtures with aluminium and arsenic compounds can form arsine. Contact with some metals (such as aluminium, tin, lead and zinc) can generate hydrogen. 1.10 Hazard/risk classification Corrosive. 1.11 Uses Sodium hydroxide is used to neutralise acid solutions and make sodium salts. It is used in the manufacture of rayon, mercerised cotton, soap, paper, aluminium, petroleum products and in metal cleaning, electrolytic extraction of zinc, tin plating and oxide coating. Sodium hydroxide solutions hydrolyze fats to form soaps, they precipitate bases and most metals (as hydroxides) from aqueous solutions of their salts. Sodium hydroxide is a common constituent of many household and industrial cleaners including oven cleaners and beerline cleaners. It is present as a stabilising agent in bleach. It may also be found in dishwasher detergents. Some paint strippers and drain cleaners contain sodium hydroxide. It is used as a pipe line cleaner in dairies, bars and public houses. Small amounts of sodium hydroxide are produced as a by-product and released into the car interior when motor car air bag systems are activated. Air bag systems are triggered when a sensor in the bumper sends an electrical charge to a gas generator containing sodium azide (70 g). A chemical reaction is initiated that produces nitrogen gas from the sodium azide. Sodium hydroxide is present in Clinitest(R) tablets which are used by diabetics as an in vitro semiquantitive test for glycosuria. 1.12 Toxicokinetics 1.12.1 Absorption Sodium hydroxide is not absorbed. Alkalis act at the site of contact. 1.12.2 Distribution Not applicable. 1.12.3 Metabolism Not applicable. 1.12.4 Elimination Not applicable. 1.12.5 Half-life Not applicable. 1.12.6 Special populations Not applicable. 2 SUMMARY 3 EPIDEMIOLOGY OF POISONING Sodium hydroxide burns, whether dermal, ocular or gastrointestinal, are potentially very serious and may cause severe complications requiring repeated or prolonged hospitalisation and long term treatment. Ingestion Sodium hydroxide is the most commonly ingested strong alkali. The majority of cases of ingestion are accidental, particularly in children (Christesen, 1994a; Clausen et al, 1995; Gandhi et al, 1989; Edmonson, 1987; Crain et al, 1984; Grenga, 1983; Tewfik and Schloss, 1980; Lane, 1975; Ashcraft and Padula, 1974; Leape et al, 1971) where severe effects are relatively rare but potentially devastating. Adults may also ingest sodium hydroxide accidentally often mistaking it for something else (Meredith et al, 1988; Chen et al, 1988; Thompson, 1987) or where it has been transferred to a different, poorly labelled container. This may also occur in children (Friedman, 1987) Oral burns have also occurred in a child after she put an oven cleaner pad in her mouth (Vilogi et al, 1985). Sodium hydroxide has been used as a means of suicide both from drinking the solution (Winek et al, 1995; Christesen, 1994b; Arif and Karetzky, 1991; Hendrickx et al, 1990; Rabinowitz et al, 1990; Ferguson et al, 1989; Rubin et al, 1989; Estrera et al, 1986; Crain et al, 1984; Cello et al, 1980; McCabe et al, 1969; Matenga et al, 1987; Oakes et al, 1982; Okonek et al, 1981; Balasegaram, 1975) and from ingestion of capsules filled with sodium hydroxide (Carroll et al, 1994; Nelson et al, 1983; Gill et al, 1986; Oakes et al, 1982; Lowe et al, 1979). A number of these cases, particularly those involving ingestion of sodium hydroxide solution have been fatal (Rabinowitz et al, 1990; Matenga et al, 1987; Estrera et al, 1986; McCabe et al, 1969). In a review of 214 cases of caustic ingestion (including bleach and acids as well as alkalis), children aged five years and under, accounted for 39% of admissions but only 8% of the burns required treatment, whereas adults constituted 48% of admissions with 81% of the burns requiring treatment (Hawkins et al, 1980). Of the 20 strictures reported in this study, 16 were due to ingestion of sodium hydroxide (12 following ingestion of sodium hydroxide solution). Clinitest(R) tablets Ingestion of Clinitest(R) tablets may occur accidentally (O'Connor et al, 1986; Schlatter-Lanz, 1985; Burrington, 1975; Payten, 1972; Mallory and Schaefer, 1977) particularly by children or the elderly or intentionally as a means of suicide (Schlatter-Lanz, 1985; Lowe et al, 1979). Often adults take the tablets with water which may reduce the incidence of severe oesophageal injury in this group, however there is also the risk of gastric injury. Death from an oesophago-aortic fistula has been reported in an elderly woman who accidentally took two tablets with tea (O'Connor et al, 1986). Ingestion of Clinitest(R) tablets was a much more common problem in the past. A number of cases were reported in the literature in the 1950s and 1960s (as reviewed by Lacoutre et al, 1986). Dermal exposure Dermal exposure to sodium hydroxide may occur following accidents in the industrial (O'Donoghue et al, 1996; Lee and Opeskin, 1995) or domestic setting (Lorette and Wilkinson, 1988; O'Donoghue et al, 1996). Dermal exposure to oven cleaner pads has also resulted in injury (Vilogi et al, 1985). Chemicals are a relatively uncommon cause of burns requiring treatment in a burns unit, but of these, sodium hydroxide is the most commonly implicated chemical. Of 3,251 patients admitted to a regional burns unit 100 (3.1%) had sustained chemical burns, which accounted for 16.5% of industrial burning accidents. Alkaline materials caused 37% of the accidents, 26% were due to sodium hydroxide, acids accounted for 27% of the burns with hydrofluoric acid involved in half these cases (Herbert and Lawrence, 1989). Alkali burns may initially appear superficial which can lead to a delay in treatment. Ocular burns Most alkaline burns to the eye occur at work (Moon and Robertson, 1983; Pfister and Koshi, 1982), but domestic accidents also account for a large proportion of ocular burns, particularly in children (Moon and Robertson, 1983). The most severe injuries are seen in men of working age (Nelson and Kopietz, 1987). Alkalis have also been used in assault (Beare, 1990a). Ocular injury has also been reported from accidental instillation of a sodium hydroxide solution into the eye instead of a contact lens solution (Mauger, 1988) and from exposure to sodium hydroxide in oven cleaner pads (Vilogi et al, 1985). Motor car air bags Small amounts of sodium hydroxide are produced as a by-product and released into the car interior when motor car air bag systems are activated. There have been reports of both ocular (White et al, 1995; Smally et al, 1992; Swanson-Biearman et al, 1993; Ingraham et al, 1991) and dermal burns (Swanson-Biearman et al, 1993) following activation of air bags during motor car accidents. 4 MECHANISM OF ACTION/TOXICITY 4.1 Mechanism Alkalis cause liquifactive necrosis with saponification of fats and solubilisation of proteins. There is a decrease in the collagen content of tissue and saponification of cell membrane lipids and cellular death. They are also hygroscopic and will absorb water from the tissues. These effects result in adherence and deep penetration into the tissues. Ingestion Alkalis cause the most severe corrosive effects on the oesophagus, rather than the stomach as is the case with acids. However, following deliberate ingestion of a large quantity of an alkali (as with intentional ingestion in adults) both the stomach and small intestine may be involved. This is particularly the case with liquid sodium hydroxide. Oesophageal changes can be divided into 3 stages: 1) acute necrotic phase in which cell death occurs due to coagulation of intracellular protein, 2) intense inflammatory reaction in viable tissues surrounding the necrotic area, thrombosis of vessels occurs, 3) sloughing of superficial necrotic layer 2-4 days later (Adam and Birck, 1982). Strictures form due to an intense fibroblastic reaction and superficial granulation tissue formation that terminates with extensive scar formation and luminal narrowing. The newly formed collagen contracts both cirumferentially and longitudinally resulting in oesophageal shortening and stricture formation. Clinitest(R) tablets The sodium hydroxide in these tablets reacts with the saliva and liberates heat which can produce a full thickness burn of the oesophagus. Clinitest(R) tablets also adhere to the oesophagus either because of thermal coagulation or because of the carbon dioxide bubbles produced from the reaction of the citric acid and sodium hydroxide present (Burrington, 1975). Gastric injury may also occur. Ocular burns Alkali burns of the eye are very serious because they cause disruption of the protective permeability barriers and rapidly penetrate the cornea and anterior chamber. They combine with cell membrane lipids which causes disruption of the cells and stromal mucopolysaccharides with concomitant tissue softening. Sodium hydroxide can pass freely through the cornea and cause damage to all layers of the cornea and to the anterior segment structures in severe cases (Wright, 1982). In the acute phase the following occurs: sloughing of the corneal epithelium, necrosis of the cells of the corneal stroma and endothelium, loss of corneal mucoid, oedema of the corneal stroma and ciliary processes, ischaemic necrosis and oedema of the conjunctiva and limbal region of the sclera and infiltration of inflammatory cells into the cornea and iris. Corneal infiltration and degeneration occurs 1-3 weeks after injury (Grant and Schuman, 1993). Alkalis cause rapid loss of corneal mucoprotein. They also bind to corneal mucoprotein and collagen and the eye may remain alkaline despite prolonged irrigation due to slow dissociation of hydroxyl ions from corneal proteins. A large number of animal experiments, particularly on rabbits, have been conducted to study alkali injury to the eye and it is known from these experiments that in the rabbit eye the pH of the aqueous humour can rise to 10-11 within a few minutes or even higher in severe cases. The pH slowly falls over a period of hours, except in extreme cases (Grant and Schuman, 1993). Injury of the endothelium causes failure of the endothelial pump which normally keeps the cornea deturgesced and clear. This failure causes the corneal stroma to become oedematous and susceptible to vascularisation and scarring. When the protective sheath around collagen is damaged, collagenases produced by polymorphonuclear leucocytes infiltrate the damaged area and degrade the corneal collagen causing melting or ulceration of the stroma, formation of descemoteceles (herniation of Descemet's membrane) and perforation of the cornea. This phase is evident 3-7 days post-injury. The role of injury to blood vessels remains unclear, as with other chemical burns to the eye the blood vessels of the conjunctiva and episclera are seen to be thrombosed immediately after exposure. Both alkali and acid burns cause a transient rise in intraocular pressure due to shrinkage of the eye coats. A second phase of raised intraocular pressure may occur due to prostaglandin release and a still later phase with glaucoma due to obstruction of aqueous outflow caused by inflammation or synechiae. In severely damaged untreated burns inflammatory destruction and ulceration continues to occur for weeks or months resulting in damage ranging from dense vascular invasion to opaque scarring and corneal perforation. During the recovery process, surviving keratocytes begin to form new collagen but a decrease in available ascorbate (caused by injury to the main source in the ciliary body) is a limiting factor in this process. This lack of ascorbate may also render the cornea more susceptible to attack by oxygen free radicals. 4.2 Toxic dose The severity of injury will depend on a number of factors including the concentration of the agent, the duration of contact and the volume ingested. It is greatest where the pH is above 12. However, pH is not the only factor which determines the extent to which a substance can cause corrosive injury. Alkaline reserve (which is the amount of a standard acid solution needed to titrate an alkali to a specified pH - usually pH 8, the pH of normal oesophageal mucosa) has been found to correlate better than pH with the production of caustic oesophageal injury (Hoffman et al, 1989). Although this method is not currently used (except internally by some manufacturers to classify products as irritant or corrosive) it appears to be a better predictor of injury than pH. Alkaline reserve may also be referred to as the titratable alkaline reserve (TAR). Solid preparations and viscous liquids are also more likely to produce severe injury due to prolonged contact. Following ingestion of a small amount the injury is usually limited to the oropharyngeal region and the oesophagus. The greater the volume the greater the risk of duodenal and gastric damage. Several studies have been carried out in an attempt to correlate clinical effects and injury. Gaudreault et al (1983) found that signs and/or symptoms do not adequately predict the presence or severity of an oesophageal lesion. Crain et al (1984) found that the presence of two or more signs or symptoms (vomiting, drooling, stridor) may be a reliable predictor of oesophageal injury. In the study by Nuutinen et al (1994) prolonged drooling and dysphagia (12-24 hours) were observed to predict oesophageal scar formation with 100% sensitivity. In the study of 224 children (aged 0-14 years) by Clausen et al (1994) serious complications were due to ingestion of sodium hydroxide or a dishwasher product. Children without any signs or symptoms at the first examination did not develop stricture or epiglottal oedema. The study by Christesen (1995) also found that complications only developed in children who had ingested strong alkalis (sodium hydroxide, ammonia and dishwasher products). The author found that children with respiratory symptoms were at greater risk of developing complications and that liquid sodium hydroxide tended to cause more complications than the granular form. It was also concluded that asymptomatic patients are not at risk of complications and probably do not require endoscopy. Knopp (1979) reported that in patients with oral burns approximately one third had significant oesophageal injury, whereas 2-15% of patients with oesophageal injury had no oral burns. Clinitest(R) tablets Ingestion of 1 tablet is sufficient to cause oesophageal stricture. However, ingestion of 47 tablets over 1 month by an adult caused only gastritis and eschar formation in the lower two thirds of the stomach with full recovery (Mallory and Schaefer, 1977). 5 FEATURES OF POISONING 5.1 Acute 5.1.1 Ingestion Ingestion of sodium hydroxide may cause an immediate burning pain in the mouth, oesophagus and stomach (retrosternal and epigastric pain), with swelling of the lips. This is followed by vomiting, haematemesis, increased salivation, ulcerative mucosal burns, dyspnoea, stridor, dysphagia and shock. Oesophageal and pharyngeal oedema may occur. It should be noted that oesophageal damage may occur in the absence of oral burns (Krenzelok and Clinton, 1979; Kynaston et al, 1989). Acute complications These include gastrointestinal haemorrhage and perforation of the gut (suggested by increasing abdominal pain, persistent vomiting, direct and indirect tenderness and a rigid abdominal wall). Gastric ulcers on the greater curvature and the antrum have been reported following ingestion of capsules filled with sodium hydroxide (Gill et al, 1986; Carroll et al, 1994; Oakes et al, 1982; Lowe et al, 1979). Late complications Oesophageal stricture and pyloric stenosis may occur as late complications. Stricture formation usually begins to develop 14-21 days after ingestion. Most strictures become manifest within the first two months. Strictures may prevent an adequate nutritional intake and in severe cases patients may be unable to swallow their own saliva. Healing of oesophageal injury depends on the severity of the injury. In the study by Di Costanzo et al (1980) first degree burns healed in about a week, second degree burns in 20-30 days and third degree burns within 90 days. Gastric necrosis and stricture may occur, usually in patients who have oesophageal injury as well. Gastric injury is more likely to occur following ingestion of liquid sodium hydroxide than ingestion of the solid. The small intestine may also be involved, duodenal and colonic necrosis has also been reported with ingestion of sodium hydroxide solution (Guth et al, 1994). Oesophago-aortic fistulae and rupture of the aorta are rare complications of corrosive ingestion (Ottoson, 1981). Tracheo-oesophageal fistulae and less commonly, broncho-oesophageal fistulae, have been reported following ingestion of alkalis (McCabe et al, 1969; Sarfati et al, 1987; Allen et al, 1970). They have also been reported to form as a complication of oesophageal dilatation (Mutaf et al, 1995). The main symptoms of a tracheo-oesophageal fistula are persistent pneumonia, choking and cyanosis while feeding. Severe corrosive injury to the stomach may result in a small scarred immobile stomach and in such cases small, frequent intakes of food may be necessary to prevent dumping syndrome. Achlorhydria with reduced or absent intrinsic factor may also occur. (Dumping syndrome is a complex reaction thought to be secondary to excessively rapid emptying of gastric contents into the jejunum. Clinical effects include nausea, sweating, palpitations, syncope and diarrhoea). Alkalis are known to increase the risk of oesophageal cancer, which can occur years after the initial injury (Isolauri and Markkula, 1989; Appelqvist and Salmo, 1980; Kinnman et al, 1968). The incidence of carcinoma following oesophageal injury from sodium hydroxide is 0.8-4% - see section 9.1. Clinitest(R) tablets These are easily mistaken for oral medication and can cause severe oesophageal injury if ingested. They can become lodged in the oesophagus and cause stricture formation. Strictures are usually short and located at about the level of carina (Burrington, 1975). Death from an oesophago-aortic fistula has been reported (O'Connor et al, 1986). 5.1.2 Inhalation Pulmonary oedema may occur following inhalation of vaporised caustics. 5.1.3 Dermal On the skin alkalis can cause severe burns. The skin is discoloured brown or black which may make initial assessment of the injury difficult. There may be recurring skin breakdown over a long period (O'Donoghue et al, 1996). It should be noted that after exposure to low concentration alkalis the affected area may remain painless for several hours (Lorette and Wilkinson, 1988). 5.1.4 Ocular Sodium hydroxide is responsible for some of the most severe, blinding injuries to the eye. There is intense pain with blepharospasm. Visual acuity is decreased due to injury to the corneal epithelium and corneal oedema. In mild cases there may be sloughing of the corneal and conjunctival epithelium. In more severe cases there may be conjunctival swelling (chemosis) and necrosis with hazing or opacity of the cornea. There is a rise in intraocular pressure initially as the sclera of the eye shrinks and then due to a release of prostaglandins. Severe burns are characterised by ischaemic necrosis. This is due to reduced or absent blood flow as a result of thrombosed blood vessels which leaves the conjunctiva and sclera white. If the eye has been penetrated fibrin may be present in the anterior chamber with infiltration of inflammatory cells. The pupil may be dilated and unreactive due to damage to the sphincter and dilator muscles. Retinal damage may also occur in severe ocular burns. Assessment of the injury and a prognosis may be difficult until 48-72 hours after the exposure (Pfister and Koshi, 1982). There may be involvement of the lids with erythema, oedema or blistering or in severe cases ischaemic necrosis. Late complications of severe ocular burns include: persistent oedema, glaucoma, vascularisation of cornea, fibrous tissue scarring of cornea, growth of vessels throughout cornea, ulceration, perforation, permanent opacity, staphyloma, phthisis bulbi (shrinkage and wastage of eyeball), cataract and symblepharon (adhesion between tarsal conjunctiva and bulbar conjunctiva). 5.1.5 Other routes No data. 5.2 Chronic toxicity 5.2.1 Ingestion Clinitest(R) tablets A 71 year old woman developed gastritis and eschar formation in the lower two thirds of the stomach after accidentally ingesting 47 Clinitest(R) tablets over a period of 1 month. Her oesophagus was normal. She made a full recovery (Mallory and Schaefer, 1977). 5.2.2 Inhalation Obstructive airway disease has been reported following chronic occupational exposure to sodium hydroxide mist. The patient developed cough, dyspnoea and tachypnoea after a 20 year exposure to sodium hydroxide. The solution was used to clean jam containers which were boiled in it for two hours. He had a barrel chest with limited movements and diffuse expiratory wheezing. A chest X-ray showed severe pulmonary hyperinflation (Rubin et al, 1992). 5.2.3 Dermal No data. 5.2.4 Ocular No data. 5.2.5 Other routes No data. 5.3 Systematic description of clinical effects 5.3.1 Cardiovascular Tachycardia and hypotension may occur in patient with severe corrosive damage to the gastrointestinal tract resulting in haemorrhage or perforation. Oesophago-aortic fistulae and rupture of the aorta are rare complications of corrosive ingestion (Ottoson, 1981), they has also been reported following ingestion of Clinitest(R) tablets (O'Connor et al, 1984). Pericarditis may occur (McCabe et al, 1969; Matenga et al, 1987). 5.3.2 Respiration Acute Dyspnoea and stridor may occur and in severe cases there may be upper airway obstruction. Recurrent atalectasis and pneumonia developed in two adults who suffered bronchial burns after ingestion of sodium hydroxide (Meredith et al, 1988) Mediastinitis may occur (McCabe et al, 1969; Matenga et al, 1987; Allen et al, 1970). Tracheo-oesophageal fistulae and less commonly, broncho-oesophageal fistulae, have been reported following ingestion of alkalies (McCabe et al, 1969; Sarfati et al, 1987; Balasegaram, 1975). They have also been reported to form as a complication of oesophageal dilatation (Mutaf et al, 1995). The main symptoms of a tracheo-oesophageal fistula are persistent pneumonia, choking and cyanosis while feeding. Pulmonary oedema may occur following inhalation of vaporised caustics. Chronic Obstructive airway disease has been reported following chronic occupational exposure to sodium hydroxide mist. The patient developed cough, dyspnoea and tachypnoea after a 20 year exposure to sodium hydroxide. The solution was used to clean jam containers which were boiled in it for two hours. He had a barrel chest with limited movements and diffuse expiratory wheezing. A chest X-ray showed severe pulmonary hyperinflation (Rubin et al, 1992). 5.3.3 Neurological Neurological effects are not expected with sodium hydroxide exposure, except the psychiatric complications of patients requiring long-term therapy and the effects of inability to speak or swallow. 5.3.4 Gastrointestinal Ingestion of sodium hydroxide may cause an immediate burning pain in the mouth, oesophagus and stomach (retrosternal and epigastric pain), with swelling of the lips. This is followed by vomiting, haematemesis, increased salivation, ulcerative mucosal burns and dysphagia. Oesophageal and pharyngeal oedema may occur. It should be noted that oesophageal damage may occur in the absence of oral burns (Krenzelok and Clinton, 1979; Kynaston et al, 1989). Acute complications These include gastrointestinal haemorrhage and perforation of the gut (suggested by increasing abdominal pain, persistent vomiting, direct and indirect tenderness and a rigid abdominal wall). Gastric ulcers on the greater curvature and the antrum have been reported following ingestion of capsules filled with sodium hydroxide (Gill et al, 1986; Carroll et al, 1994; Oakes et al, 1982; Lowe et al, 1979). Late complications Oesophageal stricture and pyloric stenosis may occur as late complications. Stricture formation usually begins to develop 14-21 days after ingestion. Most strictures become manifest within the first two months. Strictures may prevent an adequate nutritional intake and in severe cases patients may be unable to swallow their own saliva. Healing of oesophageal injury depends on the severity of the injury. In the study by Di Costanzo et al (1980) first degree burns healed in about a week, second degree burns in 20-30 days and third degree burns within 90 days. Gastric necrosis and stricture may occur, usually in patients who have oesophageal injury as well. Gastric injury is more likely to occur following ingestion of liquid sodium hydroxide than ingestion of the solid. The small intestine may also be involved, dudodenal and colonic necrosis has also been reported with ingestion sodium hydroxide solution (Guth et al, 1994). Oesophago-aortic fistulae and rupture of the aorta are rare complications of corrosive ingestion (Ottoson, 1981). Tracheo-oesophageal fistulae and less commonly, broncho-oesophageal fistulae, have been reported following ingestion of alkalies (McCabe et al, 1969; Sarfati et al, 1987; Allen et al, 1970). They have also been reported to form as a complication of oesophageal dilatation (Mutaf et al, 1995). The main symptoms of a tracheo-oesophageal fistula are persistent pneumonia, choking and cyanosis while feeding. Severe corrosive injury to the stomach may result in small scarred immobile stomach and in such cases small, frequent intakes of food may be necessary to prevent dumping syndrome (Meredith et al, 1988. Achlorhydria with reduced or absent intrinsic factor may also occur. (Dumping syndrome is a complex reaction thought to be secondary to excessively rapid emptying of gastric contents into the jejunum. Clinical effects include nausea, sweating, palpitations, syncope and diarrhoea). Alkalis are known to increase the risk of oesophageal cancer, which can occur years after the initial injury (Isolauri and Markkula, 1989; Appelqvist and Salmo, 1980; Ti, 1983; Hopkins and Postlethwait, 1981; Benirschke, 1981; Kinnman et al, 1968). The incidence of carcinoma following oesophageal injury from sodium hydroxide is 0.8-4% - see section 9.1. Clinitest(R) tablets These are easily mistaken for oral medication and can cause severe oesophageal injury if ingested. They can become lodged in the oesophagus and cause stricture formation. Strictures are usually short and located at about the level of carina (Burrington, 1975), they generally take. Gastric ulcerations have also been reported (Oakes et al, 1982). A 71 year old woman developed gastritis and eschar formation in the lower two thirds of the stomach after accidentally ingesting 47 Clinitest(R) tablets over a period of 1 month. Her oesophagus was normal. She made a full recovery (Mallory and Schaefer, 1977). Death from an oesophago-aortic fistula has been reported (O'Connor et al, 1986). 5.3.5 Hepatic Jaundice with an elevated alkaline phosphatase concentration has been reported in a fatal case of sodium hydroxide ingestion. The authors postulated that biliary obstruction due to oedema, following burns of the ampulla as a possible explanation for this finding (Matenga et al, 1987). 5.3.6 Urinary No data. 5.3.7 Endocrine and reproductive system No data. 5.3.8 Dermatological Sodium hydroxide causes deep penetrating burns and necrosis. The skin is discoloured brown or black which may make initial assessment of the injury difficult. There may be recurring skin breakdown over a long period (O'Donoghue et al, 1996). Dermal alkali injuries differ from those of other burns for a number of reasons: * The injury may be painless and not be immediately evident. This initial lack of pain may lead to a delay in treatment. * Injury can progress over several hours. * Also initial assessment of the burn depth may be difficult because the skin may be discoloured brown or black within a short period of time. 5.3.9 Eye, ears, nose and throat Ocular Sodium hydroxide is responsible for some of the most severe, blinding injuries to the eye. There is intense pain with blepharospasm. Visual acuity is decreased due to injury to the corneal epithelium and corneal oedema. In mild cases there may be sloughing of the corneal and conjunctival epithelium. In more severe cases there may be conjunctival swelling (chemosis) and necrosis with hazing or opacity of the cornea. There is a rise in intraocular pressure initially as the sclera of the eye shrinks and then with a release of prostaglandins. Severe burns are characterised by ischaemic necrosis. This is due to reduced or absent blood flow as a result of thrombosed blood vessels which leaves the conjunctiva and sclera white. If the eye has been penetrated fibrin may be present in the anterior chamber with infiltration of inflammatory cells. The pupil may be dilated and unreactive due to damage to the sphincter and dilator muscles. Retinal damage may also occur in severe ocular burns. Assessment of the injury and a prognosis may be difficult until 48-72 hours after the exposure (Pfister and Koshi, 1982). There may be involvement of the lids with erythema, oedema or blistering or in severe cases ischaemic necrosis. Late complications of severe ocular burns include: persistent oedema, glaucoma, vascularisation of cornea, fibrous tissue scarring of cornea, growth of vessels throughout cornea, ulceration, perforation, permanent opacity, staphyloma, phthisis bulbi (shrinkage and wastage of eyeball), cataract and symblepharon (adhesion between tarsal conjunctiva and bulbar conjunctiva). 5.3.10 Haematological Neutropaenia and thrombocytopenia have been reported in a fatal case of sodium hydroxide ingestion (Matenga et al, 1987). 5.3.11 Immunological No data. 5.3.12 Metabolic 5.3.12.1 Acid-base disturbances Lactic acidosis may occur in severe cases due to tissue damage and shock (Okonek et al, 1981). 5.3.12.2 Fluid and electrolyte disturbances None. 5.3.12.3 Other None. 5.3.13 Allergic reactions No data. 5.3.14 Other clinical effects None. 5.4 At risk groups 5.4.1 Elderly Since the elderly are not involved in occupations involving sodium hydroxide they are at less risk of exposure. However they may still be exposed in the domestic setting or from motor car air bags. Accidental ingestion of Clinitest(R) tablets is also a problem in this age group. 5.4.2 Pregnancy Not applicable. 5.4.3 Children Children are at particular risk of exposure to sodium hydroxide in the home where they may sustain dermal, ocular or gastrointestinal injury. Ocular injury has been reported in a child following activation of an motor car air bag (Ingram et al, 1991). Children are also at risk from accidental ingestion of Clinitest(R) tablets. 5.4.4 Enzyme deficiencies Not applicable. 5.4.5 Enzyme induced Not applicable. 5.4.6 Occupations There is a risk of exposure to sodium hydroxide in a number of occupations including chemical workers, those involved in the manufacture of sodium hydroxide and cleaners using sodium hydroxide containing products. 5.4.7 Others Dermal (Swanson-Biearman et al, 1993) and ocular (White et al, 1995; Smally et al, 1992; Swanson-Biearman et al, 1993) burns have been reported from exposure to sodium hydroxide following activation of motor car air bags. 6 MANAGEMENT 6.1 Decontamination Ingestion Gastric lavage and emesis are contraindicated because of the risks of further injury on re-exposure of the oesophagus. Nasogastric aspiration of the stomach contents is probably less effective for ingestion of alkali than for acids, since alkalis tend to damage the oesophagus rather than the stomach. Oral fluids should be given (Homan et al, 1994) unless there is evidence of severe injury. Neutralising chemicals should never be given because heat is produced during neutralisation and this could exacerbate any injury (Rumack and Burrington, 1977). Ingestion of Clinitest(R) tablets Orange juice or milk should be given to drink as soon as possible after ingestion of a Clinitest(R) tablet as this reduces the rate of release of heat of reaction. Water should be given if milk is not available. Even late administration of diluents may be beneficial because of the non-uniform break up of tablets (Lacoutre et al, 1986). Ocular Copious and immediate irrigation of exposed eyes is essential. Water (preferably sterile) or normal saline may be used, although other solutions have been employed in an emergency including tap water, Hartmans solution and universal buffer solution. Particulate matter should be removed with cotton wool buds or forceps. The pH of the cornea and irrigating fluid from the eye should be monitored with universal indicator paper. Irrigation should be continued until the pH of the eye is normal and remains so for 2 hours. Pain and blepharospasm may make irrigation difficult and the use of anaesthetic drops (e.g. amethocaine, lignocaine) may be needed to facilitate thorough irrigation. A lid speculum may be used if required. It is essential that the whole eye is irrigated including under the upper and lower lids. The use of an irrigating contact lens or an anterior chamber tap (paracentesis) have also been recommended (Nelson and Kopietz, 1987; Pfister and Koshi, 1982). Dermal All contaminated clothing must be removed. Copious irrigation of the skin should be commenced immediately. If an extensive area has been exposed whole body irrigation should be undertaken preferably using a high-flow shower unit. The burnt areas should then be covered with wet compresses during transfer to hospital (Herbert and Lawrence, 1989). See supportice care for further details. 6.2 Supportive care Ingestion Asymptomatic/mildly symptomatic patients It should be noted that oesophageal damage may occur in the absence of oral burns (Krenzelok and Clinton, 1979; Kynaston et al, 1989). These patients must be admitted for observation until the extent of the injury (if any) can be determined. Oral fluids may be given if the patient is willing to drink. Oral feeding should be maintained if the patient is able to tolerate it, otherwise tube feeding or parenteral nutrition should be provided. On discharge all patients must be advised on the possibility of late onset sequelae and advised to return if necessary. Severely affected patients Treatment is supportive. In severely affected patients aggressive intervention is essential (Meredith et al, 1988; Hendrickx et al, 1990; Andreoni et al, 1995). Urgent assessment of the airway and endoscopic evaluation is required (see section 6.6 Investigations). A supraglottic-epiglottic burn with erythema and oedema is usually an sign that further oedema will occur which will lead to airway obstruction and is an indication for early intubation or tracheostomy (Meredith et al, 1988). See section 6.7 Management controversies. Give plasma expanders/intravenous fluids for shock and check and correct the acid/base balance. Analgesia will almost certainly be needed. Intubation and ventilation may be necessary for patients with respiratory distress. Appropriate antibiotic therapy should be given if necessary. Parenteral feeding will be necessary. Late complications Strictures that prevent adequate nutritional intake and do not respond to dilatation require oesophagectomy and colonic interposition. Oesophageal strictures which result in a lumen >10mm do not impede normal life and should not require intervention (Sarfati et al, 1987). Surgical intervention may also be required for gastrointestinal perforation or haemorrhage. There may be loss of speech and inability to swallow as a result of severe corrosive injury. Speech and swallowing rehabilitation is a complex subject and is discussed by Shikowitz et al (1996) with description of the surgical techniques used and the tools used to determine the success of the reconstruction. Severe cases of sodium hydroxide ingestion may result in long-term hospitalisation and repeated surgical procedures. Psychological support is recommended. Ocular After irrigation further treatment is aimed at preventing optic nerve damage from raised intraocular pressure and to protect the cornea from ulceration, perforation and infection (Nelson and Kopietz, 1987). Raised intraocular pressure can be managed with topical beta-blockers (e.g timolol). Broad spectrum antibiotic drops (e.g. gentamicin, chloramphenicol) are recommended in cases of epithelial damage. Delayed epithelial healing is common after severe alkali burns and the use of 'bandage' soft contact lenses have been recommended to speed up the process (Nelson and Kopietz, 1987; Pfister and Koshi, 1982). Mydriatic drops, such as atropine, may alleviate pain but a short acting mydriatic may be better, particularly in the elderly who are at risk of glaucoma from mydriasis (Beare, 1990b). In the long-term care of chemical injuries to the eye the main problem is dry eyes due to damage to the Meibomian glands, presence of mucin- secreting globlet cells on the eye surface or scarring of the tear ducts. The use of tear film substitutes (e.g. hypromellose drops) may be beneficial in such cases. Chronic glaucoma and recurrent epithelial breakdown are other common problems and make patients with alkali damaged corneas poor candidates for corneal grafting. Corneal grafting should not be attempted until 12-18 months after the injury once the inflammatory response has settled. The failure rate is high, about 50-70% (Pfister and Koshi, 1982) because of the reasons stated above. In cases where grafting fails a keratoprosthesis is a last resort but this has a high complication and failure rate (Pfister and Koshi, 1982). Plastic surgery may be required for correction of other problems including cicatricial lid deformities, trichiasis (ingrowing eyelashes) and symblepharon. See also section 6.7 Management Controversies. Dermal On arrival at hospital analgesia, oxygen therapy and intravenous fluid replacement should be commenced if the clinical condition of the patient warrants it. Assessment of the depth and extent of injury is not reliable at an early stage. The most important therapy for dermal alkali injuries is prolonged copious irrigation. This effectively cleanses the wound of unreacted chemical, dilutes the chemical already in contact with tissue and restores tissue water lost to the hygroscopic effect of alkalis (Leonard et al, 1982). The earlier the irrigation is begun the greater the benefit. Irrigation should, therefore, be started as soon as possible and continued, in hospital, until the pH of the skin is no longer alkaline. In the 273 cases reported by Bomberg et al (1965) irrigation was continued for between 6 hours and 6 days (mean 24 hours). In this study, irrigation was shown to reduce the length of stay in hospital, the time to grafting and the number of cases requiring surgery. Irrigation of the injury site at the scene of the accident has also been shown to decrease the incidence of full thickness skin loss and to significantly reduce hospital stay and morbidity (Leonard et al, 1982). Testing the pH of the skin immediately after irrigation may be misleading. It is recommended that 15 minutes elapse before this is undertaken to allow residual alkali to diffuse up from the deeper regions of the dermis (Herbert and Lawrence, 1989; O'Donoghue et al, 1996). Spontaneous separation of the eschar (the slough produced by a burn) following a chemical burn takes about 30 days, which is much longer than with thermal burns. Waiting for this to occur prolongs treatment and O'Donoghue et al (1996) recommend irrigation followed by early excision of the injury site followed by immediate skin grafting for the best results. (Debridement is the removal of foreign material or dead skin from or adjacent to a traumatic or infected lesion until healthy tissue is exposed). Referral to a burns unit is recommended. 6.3 Monitoring Ingestion/dermal exposure In severely affected patients it will be necessary to monitor the airway and respiratory status and blood gases. The patient should also be monitored for signs of shock. Ocular exposure Intraocular pressure should be monitored. 6.4 Antidotes None relevant. 6.5 Elimination techniques None relevant. 6.6 Investigations Ingestion Abdominal and chest X-rays need to be taken to check for perforation. Endoscopic examination If facilities allow gastro-oesophagoscopy should be undertaken to assess the extent and severity of the injury. This procedure can be safely undertaken within 9-96 hours of the ingestion. It should be avoided 5-15 days post-ingestion because this is the time period over which the tissues slough and there is increased risk of perforation. Endoscopy is contraindicated in patients with third degree burns of the hypopharynx, burns involving the larynx or those with respiratory distress. Where there is complete obliteration of the oesophageal lumen the procedure should be terminated and repeated 48 hours later (Ali Zargar et al, 1991). Traditionally the endoscopist terminates the procedure at the first deep, penetrating and/or circumferential burn because of the risk of perforation. However with a flexible endoscopy the stomach and small intestine (panendoscopy) can be examined regardless of the presence of second or non-perforating third degree burns to the oesophagus (Ford, 1991). Ali Zargar et al (1991) recommend examination of the stomach and the first part of the duodenum. Pharyngolaryngoscopy and bronchoscopy are also recommended in severely affected patients. Laparotomy evaluation of the gastrointestinal tract beyond the oesophagus may also be indicated if there are second or third degree circumferential burns of the oesophagus (Meredith et al, 1988). Oesophageal burns are generally classified by the following description (Ford, 1991): * first degree - erythema and oedema. * second degree - erythema, blistering, superficial ulceration, fibrinous exudate. * third degree - erythema, deep ulceration, friability, eschar formation, perforation. First degree burns do not cause strictures, second degree burns result in strictures in 15-30% of cases but third degree injury results in stricture formation in over 90% of cases (Howell, 1986). Follow up appointments should be made on discharge because of the risk of delayed damage and the patient should be advised to return in the meantime if there is any evidence of oesophageal stricture (suggested by vomiting, weight loss, bloating and anorexia). Patients who develop strictures will require monitoring for life for the development of malignant disease of the oesophagus. Ocular Ophthalmological referral is essential for alkali burns to the eye. Visual acuity and intraocular pressure should be checked if possible. The eye stained with fluorescein since this will reveal the full extent of conjunctival and corneal epithelial loss (Beare, 1990b). 6.7 Management controversies Ingestion Management of severe corrosive injury Although it is agreed that the aim of initial management is the prevention of strictures, there is no consensus on the management of severe corrosive injury to the oesophagus and stomach. A number of very useful reviews have been published on the subject (Shaffer et al, 1994; Andreoni et al, 1995; Ford, 1991; Moore, 1986; Postlethwait, 1983; Klein-Schwartz and Oderda, 1983; Knopp, 1979). There is no question of the value of endoscopic investigation to determine the extent and severity of the injury although there is some debate on the relative usefulness of different types of endoscope (rigid and flexible). Some authors recommend early aggressive treatment (Andreoni et al, 1995; Hendrickx et al, 1990; Meredith et al, 1988; Gossot et al, 1987; Thompson, 1987; Estrera et al, 1986; Kirsh et al, 1978; Allen et al, 1970) while others recommend more conservative therapy (Ribet et al, 1990), particularly in children (Gandhi et al, 1989; Rappert et al, 1993; Gundogdu et al, 1992). Oesophagogastrectomy or gastrectomy (partial or total) has been recommended for large areas of necrosis to prevent perforation and subsequent peritonitis or mediastinitis. In practice this will only be necessary in a small number of patients. In the experience of Gossot et al (1987), which includes ingestion of acids as well as alkalies, a necrotic stomach always leads to perforation. There is also the risk of fistula formation which can occur between the oesophagus and the trachea, bronchus or aorta. Gossot et al (1987) found a high mortality rate with oesophagectomy performed transthoracically (76%) and recommend the removal of a necrotic oesophagus by a transhiatal blunt dissection and stripping technique. In the small number of patients on which this was performed the mortality rate was 38%. The authors suggest that the avoidance of thoracotomy may prevent the occurrence of tracheobronchial lesions. Meredith et al (1988) recommend gastrostomy with placement of a string to guide future dilatations for patients not undergoing gastrectomy or oesophagogastrectomy. Early implacement of a intraluminal stent has also been recommended to prevent the formation of strictures (Estrera et al, 1986; Wijburg et al, 1989). Gandhi et al (1989) recommend the use of string-guided oesophageal dilatation with endoscopically guided steroid injection as a safe and reliable method for the treatment of oesophageal strictures in children. In these cases there was no need for oesophageal replacement or resection in most patients. In the study by Gundogdu et al (1992) it was found that conservative treatment of strictures was more successful in children under 8 years of age. The use of steroids and antibiotics in the management of corrosive oesophageal injury Steroids have an anti-inflammatory effect and decrease fibroblastic activity and scar tissue formation. Animal data has demonstrated that strictures formed in subjects given steroids have been less well structured with fewer inflammatory changes and less fibrin deposition (Spain et al, 1950; Rosenberg et al, 1953). The use of steroids for corrosive injury in man is a controversial subject which has generated a huge amount of literature. Middlekamp et al (1969) reported thirty-two cases of oesophageal burns due to alkali injury, none of the patients with first degree burns (nineteen cases) developed oesophageal stricture. One patient (out of six) with second degree burns and all patients with third degree burns (seven) developed oesophageal stricture. In a study by Anderson et al (1990) on the use of steroids in children with corrosive injury of the oesophagus, of one hundred and thirty-one children sixty had oesophageal burns. Of these burns, fifty-five were caused by known agents, 91% of which were alkaline. Oesophageal stricture developed in ten of the thirty-one children treated with steroids and in eleven of the twenty-nine controls. Nine of the ten patients in the steroid group had third degree burns and one had second degree injuries, all eleven patients in the control group had third degree burns. Twenty-one patients given steroids and eighteen controls did not develop strictures, of these children all but one had first or second degree injuries. Several authors have found that it is the depth of the initial burn rather than the initial treatment which determines the outcome (Anderson et al, 1990; Moazam et al, 1987; Webb et al, 1970; Oakes et al, 1982). The main aim of the management of alkali injury is to reduce stricture formation. The role of steroids in alkali injury is still the subject of much debate, however most authors agree that patients with first degree burns do not require steroids since these burns usually heal without stricture formation. The difficulty here is determining the severity of the injury from oesophagoscopy since it is difficult to determine the depth of the burn and the endoscope cannot be passed beyond the first identified burn due to the risk of perforation. Some burns are so severe and extensive that strictures may develop despite steroid therapy (Haller et al, 1971) and may be delayed (Middlekamp et al, 1969). In summary, steroids are probably most effective for second degree or moderately severe burns (Klein-Schwartz and Oderda, 1983; Hawkins et al, 1980; Webb et al, 1970). They are not necessary for first degree burns and appear to be ineffective in preventing stricture formation following third degree burns. However, there is no clinical evidence that steroid therapy is more effective than non-steroid therapy in reducing oesophageal stricture in any patient, even those with second degree burns. Some authors believe there is no place for steroid therapy in the management of corrosive injury (Wijburg et al, 1989; Di Costanzo et al, 1980). As Oakes et al (1982) state, clinicians should not feel compelled to institute steroid therapy for caustic oesophagitis simply because it is considered 'standard therapy'. Contraindications and problems in steroid therapy It should be noted that there are definite contraindications to the use of steroids, these are as follows:- a) active infection b) perforation of the gastrointestinal tract or secondary mediastinitis c) significant gastrointestinal bleeding d) history of or active ulcer Steroids depress the immune system and as a result the patient is more susceptible to infection. Also steroids may mask the signs and symptoms of infection as well as those of perforation and peritonitis. Steroid therapy may also result in a thin-walled oesophagus vulnerable to perforation due to reduced wound healing and scar formation (Cardona and Daly, 1971). When to begin therapy Once the decision has been made to use steroids therapy should be started within 24-48 hours of the injury because the major inflammatory insult occurs within the first 48 hours and after this time steroids have little antifibroblastic activity. Therapy started later may reduce scar formation but all evidence indicates that the best results are obtained with early institution of therapy (Haller et al, 1971). The short duration of steroid therapy should not produce a significant reduction in intrinsic steroid production or alter the metabolic balance. Antibiotics Antibiotics should be used in all patients with evidence of infection. Some authors suggest that prophylactic antibiotics should be given in patients on steroid therapy (Howell et al, 1992; Hoffman et al, 1990; Adam and Birck, 1982), but others considered this unnecessary (Wijburg et al, 1989; Klein-Schwartz and Oderda, 1983; Wijburg et al, 1985) since the risk of infection is low (Knopp, 1979). Lathyrogens Lathyrogens are drugs which decrease the strength of collagen fibres through interruption of the covalent crosslinks between newly formed collagen molecules. Although animal data has demonstrated that lathyrogens are effective in preventing stricture formation (Butler et al, 1977) their efficacy in man is as yet undetermined (Moore, 1986). Ocular burns A number of substances have been investigated in the treatment of alkali burns of the eye with the aim of reducing the severity of damage. Ascorbate (ascorbic acid) Ascorbate is required for the formation of collagen and production is reduced when the ciliary body is damaged by alkali burns. It may also act as a scavenger of free radicals released by the infiltrating polymorphonuclear leucocytes. Animal experiments with systemic and topical ascorbate has produced conflicting results (Grant and Schuman, 1993; Pfister, 198; Pfister et al, 1982). Wright (1982) suggests the use of 10% sodium ascorbate drops hourly by day for 4-6 weeks. Systemic ascorbate may also be given (1g daily), but topical ascorbate is favoured over systemic because damage to the ciliary epithelium impairs transport of ascorbate across the blood-aqueous barrier. Collagenase inhibitors These have been used because there is evidence that collagenases released by infiltrating polymorphonuclear leucocytes can cause the breakdown of corneal stroma. Various agents have been tried including cysteine, acetylcysteine, sodium and calcium EDTA, penicillamine. Animal experiments have produced conflicting results (Wright, 1982; Grant and Schuman, 1993) and there are currently no recommendations for the use of collagenase inhibitors in alkali injury to the eye. Sodium citrate Citrate is thought to prevent the degranulation of polymorphonuclear leucocytes and thereby reduce the production of free radicals and proteolytic enzymes, and it has been suggested that the use of topical 10% citrate may be beneficial in the treatment of alkali-induced corneal ulcers (Pfister et al, 1988). Steroids Steroid therapy in the treatment of alkali-induced ocular injury is controversial. Is should only be considered for the treatment of severe burns. Wright (1982) suggests topical steroid therapy in cases of severe burns but only where stromal melting is absent and then to change to a collagenase inhibitor such as sodium citrate. However, clinical data to support their use is lacking and Pfister and Koshi (1982) advise avoiding topical steroids where possible because they interfere with the healing process. Prostaglandin inhibitors Prostaglandins are important in the recruitment of polymorphonuclear leucocytes but an effective topical prostaglandin preparation is not readily available and data on the benefit of such therapy is lacking. Numerous other treatments have been recommended (as reviewed in Grant and Schuman, 1993) but with no outstanding success. 7 CASE DATA Literature Case 1: Accidental ingestion, child A 16 month old female refused to drink and began drooling after ingesting the residue of a sodium hydroxide solution which the mother had been using for cleaning. She vomited several times with the vomitus containing a small amount of blood. The pharynx was red and there was slight bleeding of the upper gums. The chest was initially clear but 90 minutes after admission inspiratory and expiratory wheezes were present and a chest X-ray suggested aspiration pneumonia. At 15 hours post-ingestion laryngoscopy and oesophagoscopy were performed. The false cords and epiglottis were found to be red and oedematous. The cricopharyngeus was ulcerated and bleeding. The oesophageal mucosa was bleeding and circumferential second and third degree burns were present. The child required intubation and ventilation and was started on methylprednisolone and ampicillin. Ventilatory support was necessary for three weeks. Subsequent laryngoscopy revealed laryngeal oedema and burns which resulted in laryngeal stenosis. An oesophagoscopy at five weeks post-ingestion revealed oesophageal narrowing. A barium swallow showed multiple oesophageal strictures and hypoperistalsis of the proximal segment of the oesophagus. The child required nine oesophageal dilatations, and was eventually able to take oral feedings. She was discharged one year after the ingestion (Klein-Schwartz and Oderda, 1983). Case 2: Accidental ingestion, fatal A 14 year old boy took a sodium hydroxide solution (30%) in to his mouth. He immediately spat it out. He drank some milk and water and vomited. On arrival about 30 minutes later he had retrosternal pain and had difficulty swallowing. He was given antibiotics and steroids. Oesophagoscopy was performed two days later and revealed mucosal lesions in the upper oesophagus. He began to improve and was able to take mashed food orally. He then began to develop difficulty in swallowing and a X-ray on day 23 revealed a stricture at the level of the carina of trachea. On the 38th day oesophagoscopy with dilatation of the stricture was performed. About 2 hours later he suffered immediate retrosternal pain. An X-ray showed perforation of the stricture. This was sown up via a left side thoracotomy. Serious inflammatory changes were observed with mediastinal emphysema and a purulent pleuritis. A nasogastric tube and three drains were left in place. On the 44th day after ingestion profuse bleeding was observed through the nasogastric tube and drains was noted. He became shocked and the decision was made to operate. He suffered a cardiac arrest while general anaesthetic was being given. A right side thoracotomy showed a 4-5 mm rupture of the descending part of the aorta with bleeding into the left pleura. After cardiac massage, blood transfusion and repair of the rupture he stabilised. Part of the oesophagus was removed due to inflammation. On day 52 another haemorrhage occurred. He was operated on again and the haemorrhage was seen to arise from the aortic rupture. The aorta wall was fragile and could not be repaired. The patient died on the operating table. A purulent mediastinitis, bilateral purulent pleuritis, lung atalectasis and pericarditis were observed at postmortem (Ottoson, 1981). Case 3: Accidental ingestion, adult A 19 year old male vomited immediately after ingestion of 2 mouthfuls of sodium hydroxide. He had drunk it thinking it was wine. He was seen in hospital within 6 hours. He had deep oral and hypopharyngeal burns, full thickness necrosis of the entire oesophagus and stomach and mucosal burns of the bronchus. He required an emergency treacheostomy and oesophagogastrectomy with establishment of a cervical oesophagostomy. A chimney jejunostomy was constructed to provide access for enteral feeding. His post-operative course was complicated by recurrent atelectasis and pneumonia secondary to the bronchial burns, bowel obstruction and wound complications. He was discharged 6 weeks after the incident with a tracheostomy and jejeunostomy. He developed dense scarring and stenosis of the hypopharynx which required multiple laser excisions to restore pharyngeal lumen. After 9 months he underwent oesphagagogastric reconstruction with an antiperistaltic left colon interposition from the hypopharynx to the duodenum. Supraglottic scarring required further laser excisions and dilatations over the next 18 months. More than 2 years after the event, he was eating a normal diet and speaking clearly but still occasionally required dilatation of the pharynx (Meredith et al, 1988). This patient was one of nine individuals (aged 15-25 years) who sustained severe corrosive injury to the stomach and oesophagus after drinking sodium hydroxide solution in mistake for wine. The solution had been kept in the fridge for the making of pretzels. The container resembled a wine bottle and was labelled in German (Meredith et al, 1988; Chen et al, 1988; Thompson, 1987). Case 4: Clinitest(R) ingestion, fatal A 77 year old partially deaf diabetic woman accidentally swallowed 2 Clinitest(R) tablets. There was no evidence of oropharyngeal ulceration. She was given milk to drink and discharged the next day. She returned 2 weeks later with increasing dysphagia and could only swallow fluids. An endoscopy revealed an oesophageal stricture. She died three days later after a massive haematemesis. Postmortem revealed an ulcer in the upper oesophagus which had penetrated and perforated the aortic wall to form a oesophago-aortic fistula. There was no evidence of pharyngeal or gastric ulceration (O'Connor et al, 1984). Case 5: Clinitest(R) ingestion, child A 17 month old child was brought to hospital because of increasing dysphagia of 2 weeks duration. Clinitest(R) tablets were kept in the home. A barium swallow revealed a short oesophageal stricture. Repeated dilatation were of no lasting benefit even after gastrostomy and passage of a string through the oesophagus. After 19 dilatations in 3 months she underwent resection and primary anastomosis. Post-operatively she required 8 dilatations over 12 months before she could eat normally (Burrington, 1975). Case 6: Ingestion of encapsulated sodium hydroxide A 31 year female was admitted to hospital after ingestion that day of 3 gelatin capsules which she had filled with sodium hydroxide drain cleaner. She complained of abdominal cramping. Endoscopy revealed ulcerative, exudative oesophagitis in the mid to distal region. There were three deep ulcers along the greater curvature of the stomach with black necrotic debris in the centre. She was given antibiotics and corticosteroids and discharged after 7 days. One month after ingestion she returned with haematemesis and melaena. Endoscopy revealed persistence of the ulcers in the stomach, one had evidence of recent bleeding. She discharged herself after 4 days. Similar gastric ulceration was observed in another patient who ingested four capsules of the same drain cleaner. These had healed by 6 weeks post-ingestion (Gill et al, 1986). Case 7: Dermal exposure, fatal A 32 year old man was working in an area of a plant were hot sodium hydroxide was being used. It is thought that he was accidentally exposed to a spray and aerosol of the alkali which caused him to run for the shower. Before he reached it he fell or collapsed into a pool of sodium hydroxide. He was found next to the shower face down. He was turned over and sprayed with copious amounts of water but was found to be dead. A postmortem was performed 40 hours later but chemical damage was observed to be progressing 3 days later, just prior to the funeral. At postmortem the cotton clothing was found to be in good condition but the leather gloves and boots were badly disintegrated. The left boot had dissolved, only the steel toe cap and sole remained. There were severe burns present, in some cases with total soft tissue destruction down to the bone. Both eyes were severely damaged with perforation of one. On the left side of the neck the skin and fat was totally absent revealing the underlying muscles and vasculature. The left side of the body was most severely damaged. There were some changes to the respiratory tract indicating a minor degree of inhalation. There was extensive epithelial loss of the tongue and the stomach wall was found to be neutral indicating ingestion of a small amount of alkali. In a re-enactment of the accident it was found that the time taken for work boots to become damaged to the same degree as the victim's under similar circumstances was about 13 minutes (Lee and Opeskin, 1995). Case 8: Dermal exposure requiring skin graft A 20 year old patient presented 2 hours after accidentally spraying herself in the face with an oven cleaner containing 4% sodium hydroxide. She had removed the excess liquid but did not irrigate the area. She did not experience any pain until nearly 2 hours later. On examination she was in moderate distress with no ocular involvement. The right side of her face was erythematous and blistering in a serpiginous pattern extending from the infraorbital rim to the body and angle of her mandible. The area of the right cheek had a bronze discolouration. The body surface area involved was about 2%. The area was irrigated for 60 minutes. Despite this the burn continued to show signs of third degree burn involvement. She was transferred to a burns unit and underwent surgical debridement and skin graft. Follow up six weeks later revealed good healing and no complications (Lorette and Wilkinson, 1988). Case 9: Ocular injury A 31 year man had sodium hydroxide blown into his amblyopic left eye after an explosion caused by placing solid sodium hydroxide into a plugged drain. He washed the eye immediately in a shower and arrived at hospital within 5 minutes. On examination the cornea was opaque and the lower two thirds of the conjunctiva was ischaemic. Topical irrigation was repeated and he was transferred to the operating room where intraocular irrigation was commenced. About 100-120ml of Ringer's solution was used in this procedure over 90 minutes. At this time the cornea was slightly clearer. Methylprednisolone was given by retobulbar and subconjunctival injection. Continuous slow topical irrigation was continued for a further 24 hours. On the first post-operative day visual acuity was present to light, intraocular pressure was high and a cataract was present. Topical antibiotics, systemic and topical corticosteroids and carbonic anhydrase inhibitors were given. Two weeks after the injury aspiration-irrigation of the cataract was undertaken with an improvement in visual acuity. Acetylcysteine drops were used and a soft contact lens was put in place. He was discharged three weeks after the injury but returned three days later with severe pain, hypopyon and hyphema. The cornea ulcerated and perforated 27 days after the injury. The perforation was repaired with a corneoscleral free hand graft. Despite the presence of light perception the eye was enucleated at the patient's request 70 days after the injury (Burns and Hikes, 1979). Internal cases 1) A 63 year old male died within 1 hour of admission after ingestion of sodium hydroxide. He had ingested 10 teaspoons in a glass of water. He developed pain in the mouth and chest and was given milk to drink. On postmortem the pH of the stomach contents was 13.4. There was blue-black discolouration of the mucosa from the lips to the pylorus. There was no perforation, but milk was found in the lungs (NPIS (London) 75/8481). 2) A 44 year old male was admitted to hospital after ingestion of 6 tablespoons of sodium hydroxide in a pint of water. He had severe burns to the lips, mouth and pharynx. Twelve hours after admission he developed laryngeal stricture and a tracheostomy was performed. His condition remained satisfactory and the tracheostomy was removed three days later. Four days after this he developed haematemesis and continued to vomit blood for a month. He required 34 pints of blood by transfusion. He began to improve after this time with occasional diarrhoea. He then lost a stone in weight and developed electrolyte problems, particularly hypokalaemia. It was thought he may have developed a gastro-colic fistula. A gastro-graffin swallow revealed narrowing of the oesophagus and of the distal part of the stomach with dye passing straight through into the ascending colon via a gastric-colonic fistula. Seven days after this a laparotomy was performed and a feeding jejunostomy tube inserted into the jejunum. He began to maintain his weight. About two weeks after this a barium meal confirmed the presence of the fistula and he was started on oral fluids. Three days later he complained of abdominal pain after ingestion of soup. There was abdominal tenderness and rigidity. A laparotomy revealed free fluid in the right para-colic gutter with an inflamed appendix. An appendectomy and partial gastrectomy were performed. Post-operatively he recovered well and was started on oral fluids. Three weeks later he developed another episode of severe abdominal pain. He deteriorated and another laparotomy showed a closed duodenal perforation. His condition remained poor with pyrexia, tachycardia and hypotension. Septicaemia was diagnosed and he was continued on ampicillin and IV fluids. He continued to deteriorate and died 3 days after the last operation, 94 days post-ingestion (NPIS (London) 73/9664) 8 ANALYSIS 8.1 Agent/toxin/metabolite Not relevant. 8.2 Sample containers to be used 8.3 Optimum storage conditions 8.4 Transport of samples 8.5 Interpretation of data 8.6 Conversion factors 8.7 Other recommendations 9 OTHER TOXICOLOGICAL DATA 9.1 Carcinogenicity Alkalis are known to increase the risk of oesophageal cancer, which can occur years after the initial injury (Isolauri and Markkula, 1989; Ti, 1983; Hopkins and Postlethwait, 1981; Benirschke, 1981; Appelqvist and Salmo, 1980; Kinnman et al, 1968). The incidence of carcinoma following oesophageal injury from sodium hydroxide is 0.8-4%. Of the fifteen patients (age range 38-83) in the study by Isolauri and Markkula (1989) twelve had accidentally swallowed sodium hydroxide at the age of two or three years, one at fifteen years and one at twenty-three years of age. The time between ingestion and the diagnosis of oesophageal cancer was 22-81 years. Appelqvist and Salmo (1980) describe similar results, out of sixty patients with oesophageal cancer for which the time of ingestion was known, fifty-two had ingested the sodium hydroxide at the age of ten years or younger. 9.2 Genotoxicity No data. 9.3 Mutagenicity 9.4 Reprotoxicity No data. 9.5 Teratogenicity No data. 9.6 ADI The acceptable daily intake is not determined. 9.7 MRL 9.8 AOEL 9.9 TLV TLV = 2 mg m-3. long term exposure limit = 5 mg m-3 (EH 40/95). 9.10 Relevant animal data Leape et al (1971) demonstrated that 5ml of a 30.5% solution of sodium hydroxide was uniformly fatal when introduced into a cat's oesophagus, even if neutralised 3 seconds later. Exposure of cat oesophagus to 8.3% sodium hydroxide for 30 seconds resulted in destruction of the superficial layer of squamous mucosa along with submucosal and transmural thrombosis in blood vessels (Ashcraft and Padula, 1974). 9.11 Relevant in vitro data 10 ENVIRONMENTAL DATA 10.1 Ecotoxicological data No data. 10.2 Behaviour No data. 10.3 Biodegradation No data. 10.4 Environmentally important metabolites None. 10.5 Hazard warnings 10.5.1 Aquatic life 10.5.2 Bees 10.5.3 Birds 10.5.4 Mammals 10.5.5 Plants 10.5.6 Protected species 10.6 Waste disposal data Sodium hydroxide may occur in waste from the following industries: soaps, cleaning compounds, pulp and paper, petroleum, mineral and vegetable oils, leather, dyes and textile dyeing, cotton, coal distillation, etc. Author Nicky Bates National Poisons Information Service (London Centre) Medical Toxicology Unit Guy's & St Thomas' Hospital Trust Avonley Road London SE14 5ER UK This monograph was produced by the staff of the London Centre of the National Poisons Information Service in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Peer review was undertaken by the Directors of the UK National Poisons Information Service. June 1996 REFERENCES Adam JS and Birck HG. 1982 Pediatric caustic ingestion. Ann Otol Rhinol Laryngol 91:656-658 Ali Zargar S, Kochhar R, Mehta S and Mehta SK. 1991 The role of fibreoptic endoscopy in the management of corrosive ingestion and modified endoscopic classificatiion of burns. Gastrointest Endosc 37:165-169 Allen RE, Thoshinsky MJ, Stallone RJ and Hunt TK. 1970 Corrosive injuries of the stomach. Arch Surg 100:409-413 Anderson KD, Rouse TM and Randolph JGH. 1990 A controlled trial of corticosteroids in children with corrosive injury of the oesophagus. N Eng J Med 323 (10):637-640 Andreoni B, Marini A, Gavinelli M, Biffi R, Tiberio G, Farina ML and Rossi A. 1995 Emergency management of caustic ingestion in adults. Surg Today 25:119-124 Appelqvist P and Salmo M. 1980 Lye corrosion carcinoma of the oesophagus. A review of 63 cases. Cancer 45:2655-2658 Arif A and Karetzky MS. 1991 Complications of caustic ingestion. N J Med J 88 (3):201-204 Ashcraft KW and Padula RT. 1974 The effect of dilute corrosives on the esophagus. Pediatrics 53 92):226-232 Balasegaram M. 1975 Early management of corrosive burns of the oesophagus. Br J Surg 62:444-447 Beare JDL. 1990a Eye injuries from assault with chemicals. Br J Opthalmol 74:514-518 Beare J. 1990b Management of chemical burns to the eye. In Major Chemical Disasters - Medical Aspects of Management. Murray V (ed). International Congress and Symposium Series 155 Royal Society of Medicine Benirschke K. 1981 Time bomb of lye ingestion? Am J Dis Child 135:17-18 Bomberg BE, Sung CL and Walden RH. 1965 Hydrotherapy for chemical burns. Plast Reconstr Surg 35:85-95 Burns RP and Hikes CE. 1979 Irrigation of the anterior chamber for the treatment of alkali burns. Am J Ophthalmol 88 (1):119-120 Burrington JD. 1975 Clinitest burns of the esophagus. Ann Thorac Surg 20 (4):400-404 Butler C, Madden JW, Davis WM and Peacock EE. 1977 Morphological aspects of experimental esophageal lye strictures. II. Effect of steroid hormones, bougienage and induced lathyrism on acute lye burns. Surgery 81:431-435 Cardona JC and Daly JF. 1971 Current mangement of corrosive esophagitis. An evaluation of results of 239 cases. Ann Otol 80:521-527 Carroll L, Agnone F and Vance M. 1994 Laproscopic evaluation after lye ingestion (abstract 140). Vet Hum Toxicol 36 (4):373 Cello JP, Fogel RP and Boland R. 1980 Liquid caustic ingestion. Spectrum of injury. Arch Intern Med 140:501-504 Chen YM, Ott DJ, Thompson JN and Gelfand DW. 1988 Progressive roentgenographic appearance of caustic esophagitis. South Med J 81 (6):724-744 Christesen HBT. 1995 Prediction of complications following unintentional caustic ingestion in children. Is endoscopy always necessary? Acta Paediatr 84:1177-1182 Christesen HBT. 1994a Epidemiology and prevention of caustic ingestion in children. Acta Paediatr 83:212-215 Christesen HBT. 1994b Caustic ingestion in adults - epidemiology and prevention. Clin Toxicol 32 (5):557-568 Clausen JO, Nielsen TLF and Fogh A. 1994 Admission to Danish hospitals after suspected ingestion of corrosives. A nationwide survey (1984-1988) comprising children aged 0-14 years. Dan Med Bull 41:234-237 Crain EE, Gershel JC and Mezey AP. 1984 Caustic ingestions. Symptoms as predictors of esophageal injury. Am J Dis Child 138:863-865 Di Costanzo J, Noirclerc M, Jouglard J, Escoffier JM, Cano N, Martin J and Gauthier A. 1980 New therapeutic approach to corrosive burns of the upper gastrointestinal tract. Gut 21:370-375 Edmonson MB. 1987 Caustic ingesion by farm children. Pediatrics 79 (3):413-416 EH 40/95 Occupational exposure limits. 1995 HSE Estrera A, Taylor W, Mills LJ and Platt MR. 1986 Corrosive burns of th esophagus and stomach: a recommendation for an aggressive surgical approach. Ann Thorac Surg 41:276-283 Ferguson MK, Migliore M, Staszak VM and Little AG. 1989 Early evaluation and therapy for caustic esophageal injury. Am J Surg 157:116-119 Ford M. 1991 Alkali and acid injuries of the upper gastrointestinal tract. in Contemporary management in critical care 1 (3):225-249 Tobin MJ and Grenvik A (eds). Churchill Livingstone Friedman EM. 1987 Caustic ingestions and foreign body aspirations: an overlooked form of child abuse. Ann Otol Rhinol Laryngol 96:709-712 Gandhi RP, Cooper A and Barlow BA. 1989 Successful management of esophageal strictures without resection or replacement. J Pediatr Surg 24 (8):745-750 Gaudreault P, Parent M, McGuigan MA, Chicoine L and Lovejoy FH. 1983 Predicability of eosophageal injury from signs and symptoms: a study of caustic ingestions in 378 children. Pediatrics 71 (5):767-770 Gill RA, Pentel PR and Merritt VE. 1986 Encapsulated alkali ingestion has a characteristic endoscopic appearance. Gastrointest Endoscopy 32 (2):121-122 Gossot D, Sarfati E and Celerier M. 1987 Early blunt esophagectomy in severe caustic burns of the upper digestive tract. J Thorac Cardiovasc Surg 94:188-191 Grant WM and Schuman JS. 1993 Toxicology of the eye 4th ed. Charles C Thomas, Springfield Illinois Grenga TE. 1983 A new risk of lye ingestion by children. N Engl J Med 308 (3):156-157 Gundogdu HZ, Tanyel FC, Buyukpamukcu N and Hicsonmez A. 1992 Conservative treatment of caustic esophageal strictures in children. J Pediatr Surg 27 (6):767-770 Guth AA, Pachter HL, Albanese C and Kim U. 1994 Combined duodenal and colonic necrosis. An unusual sequela of caustic ingestion. J Clin Gastroenterol 19 (4):303-305 Hawkins DB, Demeter MJ and Barnett TE. 1980 Caustic ingestion: controversies in management. A review of 214 cases. Laryngoscope 90:98-109 Hendrickx L, Hubens A and Van Hee W. 1990 Emergency oesophageal stripping, an aggressive approach to acute, necrotic caustic burns of the oesophagus and stomach. Acta Chir Belg 90:46-49 Herbert K and Lawrence JC. 1989 Chemical burns. Burns 15 (6):381-384 Hoffman RS, Howland MA, Kamerow HN and Goldfrank LR. 1989 Comparison of titratable acid/alkaline reserve and pH in potentially caustic household products. Clin Toxicol 27 (4&5):24261 Homan CS, Maitra SR, Lane BP, Thode HC and Sable M. 1994 Therapeutic effects of water and milk for acute alkali injury of the esophagus. Ann Emerg Med 241:14-20 Hopkins RA and Postlethwait RW. 1981 Caustic burns and carcinoma of the esophagus. Ann Surg 194:146-148 Howell JM, Dalsey WC, Hartsell FW and Butzin CA. 1990 Steroids for the treatment of corrosive esophageal injury. A statistical analysis of past studies. Am J Emerg Med 10:421-425 Howell JM. 1986 Alkaline ingestions. Ann Emerg Med 15:820-825 Ingraham HJ, Perry HD and Donnerfeld ED. 1991 Air-bag keratitis. N Engl J Med 324 (22):1599-1600 Isolauri J and Markkula H. 1989 Lye ingestion and carcinoma of the oesophagus. Acta Chir Scand 155:269-271 Kinnman J, Shin HI and Wetteland P. 1968 Carcinoma of the oesophagus after lye ingestion. Report of a case in 15 year old Korean male. Acta Chir Scand 134:489-493 Kirsh MM, Peterson A, Brown JW, Orringer MB, Ritter F and Sloan H. 1978 Treatment of caustic injuries of the esophagus. Ann Surg 188:675-678 Klein-Schwartz W and Oderda GM. 1983 Management of corrosive ingestions. Clin Toxicol Consult 5 (2):39-55 Knopp R. 1979 Caustic ingestions. JACEP 8:329-336 Krenzelok EP and Clinton JE. 1979 Caustic esophageal and gastric erosion without evidence of oral burns following detergent ingestion. JACEP 8:194-196 Kynaston JA, Patrick MK, Shepherd RW, Raivadera PV and Cleghorn GJ. 1989 The hazards of automatic dishwasher detergent. Med J Aust 151:5-7 Lacoutre PG, Gaudrealt and Lovejoy FH Jr. 1986 Clintest tablet ingestion: an in vitro investigation concerned with intial emergency management. Ann Emerg Med 15:143-146 Leape LL, Ashcraft KW, Scarpelli DG and Holder TM. 1971 Hazard to health - liquid lye. N Engl J Med 284:578-581 Lee KAP and Opeskin K. 1995 Fatal alkali burns. Forensic Sci Int 72:219-227 Leonard LG, Scheulen JJ, Munster AM. 1982 Chemical burns: effects of prompt first aid. J Trauma 22 (5):420-423 Lorette JJ and Wilkinson JA. 1988 Alkaline chemical burn to the face requiring full thickness skin grafting. Ann Emerg Med 17:739-741 Lowe JE, Graham DY, Boisaubin EV and Lanza FL. 1979 Corrosive injury to the stomach: the natural history and role of fiberoptic endoscopy. Am J Surg 137:803-806 Mallory A and Schaefer JW. 1977 Clinitest ingestion. Br Med J 2:105-107 Matenga JA, Russell J, Paul B and Thomas JEP. Suicide due to caustic soda - a case report with some unusual complications. Cent Af J Med 33 (3):77-79 Mauger T. 1988 Sodium hydroxide masquerading as a contact lens solution. Arch Ophthamol 106:1037 McCabe RE, Scott JR and Knox WG. 1969 Fistulisation between the esophageal, aorta and trachea as a complication of acute corrosive esophagitis: report of a case. Am Surg 35 (6):450-454 Middlekamp JN, Ferguson TB, Roper CL and Hoffman FD. 1969 The management and problems of caustic burns in children. J Thorac Cardiovasc Surg 57:341-347 Moazam F, Talbert JL, Miller D and Mollitt DL. 1987 Caustic ingestion and its sequelae in children. South Med J 80:187-190 Moon MEL and Robertson IF. 1983 Retrospective study of alkali burns of the eye. Aust J Opthalmol 11:281-286 Moore WR. 1986 Caustic ingestions. Pathophysiology, diagnosis and treatment. Clin Pediatr 25 (4):192-196 Mutaf O, Avanoglu A, Mevsim A and Ozok G. 1995 Management of tracheosophageal fistula as a complication of esophageal dilatations in caustic esophageal burns. J Pediatr Surg 30 (6):823-826 Nelson JD and Kopietz LA. 1987 Chemical injuries to the eyes. Emergency, intermediate and long-term care. Postgrad Med 81 (4):62-75 Nelson R, Walson P and Kelley M. 1983 Caustic ingestion. Ann Emerg Med 12:559-562 Nuutinen M, Uhari M, Karvali T and Kouvalainen K. 1994 Consequences of caustic ingestions in children. Acta Paediatr 83:1200-1205 Oakes DD, Sherck JP and Mark JBD. 1982 Lye ingestion. Clinical patterns and therapeutic implications. J Thorac Cardiovasc Surg 83:194-204 O'Connor HJ, Dixon MF, Grant AC, Sooltan MA, Axon ATR and Henry JA. 1984 Fatal ingestion of Clinitest in an a adult. J R Soc Med 77:963-965 O'Donoghue JM, Al-Ghazal SK and McCann JJ. 1996 Caustic soda burns to the extremities: difficulties in management. BJCP 50 (2):108-109 Okonek S, Bierbach H and Atzpodien W. 1981 Unexpected metabolic acidosis in severe lye poisoning. Clin Toxicol 18 (2):225-230 Ottoson A. 1981 Late aortic rupture after lye ingestion. Arch Toxicol 47:59-62 Payten RJ. 1972 Clintest tablet stricture of the oesophagus. Br Med J 4:728-729 Pfister RR. 1983 Chemical injuries to the eye. Ophthalmology 90:1246-1253 Pfister RR and Koshi J. 1982 Alkali burns of the eye: pathophysiology and treatment. South Med J 75 (4):417-422 Pfister RR, Haddox JL and Lank KM. 1988 Citrate or ascorbate/citrate treatment of established corneal ulcers in the alkali-injured rabbit eye. Invest Ophthalmol Vis Sci 29 (7):1110-1115 Pfister RR, Paterson CA and Hayes SA. 1982 Effect of topical 10% ascorbate solution on established corneal ulcers after severe alkali injury. Invest Ophthamol Vis Sci 22:382-385 Postlethwait RW. 1983 Chemical burns of the esophagus. Surg Clin N Am 63 (4):915-924 Rabinovitz M, Udekwu AO, Campbell WL, Kumar S, Razack A and Van Thiel DH. 1990 Tracheosophageal-aortic fistula complicating lye ingestion. Am J Gastroenterol 85 (7):868-871 Rappert P, Preier L, Korab Wa nd Neubauer T. 1993 Diagnostic and therapeutic management of esophageal and gastric caustic burns in childhood. Eur J Pediatr Surg 3:202-205 Ribet M, Chambon JP and Pruvot FR. 1990 Oesophagectomy for severe corrosive injuries: is it always legitimate? Eur J Cardiovasc Surg 4:347-350 Rosenberg N, Kunderman PJ, Vroman L and Moolten SE. 1953 Prevention of experimental esophageal stricture by cortisone. II. Arch Surg 66:593-598 Rubin AE, Bentur L and Bentur Y. 1992 Obstructive airway disease associated with occupational sodium hydroxide inhalation. Br J Ind Med 49:213-214 Rubin MM, Jui VJ and Cozzi GM. 1989 Treatment of caustic ingestion. J Oral Maxillofac Surg 47:286-290 Rumack BH and Burrington JD. 1977 Caustic ingestion: a rational look at diluents. Clin Toxicol 11:27-34 Shaffer RT, Carrougher JG, Kadakia SC and Levine SM.1994 Update on caustic ingestions: how therapy has changed. J Crit Ill 9 (2):161-173 Schlatter-Lanz I. 1985 Veratzungen durch Testtabletten zur semiquantitativen Harnzuckerbestimmung (Clinitest). Schweiz Rundschau Med 74 (50):1402-1406 Shikovitz MJ, Levy J, Villano D, Graver LM and Pochaczevsky R. 1996 Speech and swallowing rehabilitation following devastating caustic ingestion: techniques and indicators for success. Laryngoscope 106 (Suppl 78):1-12 Smally AJ, Binzer A, Dolin S and Viano D. 1992 Alkaline chemical keratitis: eye injury from air bags. Ann emerg med 21 (11):1400-1402 Spain DM, Molomut N and Haler A. 1950 The effect of cortisone on the formation of granulation tissue in mice. Am J Pathol 26:710-711 Swanson-Biearman B, Mvros R, Dean BS and Krenzelok EP. 1993 Air bags: lifesaving with toxic potential? Am J Emerg Med 11:38-39 Tewfik TL and Schloss MD. 1980 Ingestion of lye and other corrosive agents - a study of 86 infant and child cases. J Otolaryngol 9 (1):72-77 Thompson JN. 1987 Corrosive esophageal injuries. I. A study of nine cases of concurrent accidental caustic ingestion. Laryngoscope 97:1060-1068 Ti TK. 1983 Oesophageal carcinoma associated with corrosive injury - prevention and treatment by oesophageal resection. Br J Surg 70:223-225 Vilogi J, Whitehead B and Marcus SM. 1985 Oven cleaner pads: new risk for corrosive injury. Am J Emerg Med 3:412-414 Webb WR, Koutras P, Ecker RR and Sugg WL. 1970 An evaluation of steroids and antibiotics in caustic burns of the esophagus. Ann Thorac Surg 9:95-102 Whiter JE, McClafferty K, Orton RB, Tokarewicz AC and Nowak ES. 1995 Ocular alkali burn associated with motor car air-bag activation. Can Med Assoc J 153 (7):933-934 Wijburg FA, Beukers MM, Heymans HS, Bartelsman JF and den Hartog Jager FC. 1985 Nasogastric intubation as sole treatment of caustic esophageal lesions. Ann Otol Rhinol Laryngol 94:337-341 Wijburg FA, Heymans HSA and Urbanus NAM. 1989 Caustic esophageal lesions in childhood: prevention of stricture formation. J Pediatr Surg 24 (2):171-173 Winek CL, Rozin L, Wahba WW and Rafizadeh V. 1995 Ingestion of lye. Forensic Sci Int 73:143-147 Wright P. 1982 The chemically injured eye. Trans Ophthal Soc UK 102:85-87