CASE REPORTS

Refer to: Longstreth WT Jr, Pierson DJ: Metaldehyde poisoning from slug bait ingestion. West J Med 1982 Aug; 137:134- oculocephalic reflexes and corneal reflexes were 137 present. Tone and tendon reflexes were diffusely increased though there were flexor plantar re- sponses. Chvostek's sign was present. Laboratory testing was remarkable for an unmeasured anion gap of 23 mEq per liter, though the arterial blood Metaldehyde Poisoning gas determinations showed respiratory alkalosis with pH 7.57 and carbon dioxide partial pressure From Slug Bait Ingestion (Pco2) 21 mm of mercury. Urine pH was 5.5 with W. T. LONGSTRETH, Jr, MD ketones present. Serum calcium and magnesium DAVID J. PIERSON, MD levels were normal. Toxicologic studies on blood Seattle and gastric contents were negative except for an unidentified substance. Her hospital course was complicated by severe WE RECENTLY CARED FOR a patient with massive muscle spasms and repeated generalized convul- metaldehyde poisoning and report the case to fam- sions despite therapeutic concentrations of pheny- iliarize physicians with the toxic effects of the toin and phenobarbital in the blood. Diazepam substance, as well as to outline a rational approach administered intravenously only briefly controlled to future cases. the spasms and convulsions. Although the serum creatine kinase level was elevated to four times Report of a Case normal, significant myoglobinuria did not develop. A 32-year-old woman, a grade school teacher, She also had pneumonia, increased oral and tra- had a one-year history of depression and several cheobronchial secretions and elevated serum trans- suicide attempts. Early one morning she swallowed aminase levels, which peaked during the second approximately 470 ml (16 oz) of a commercial week and returned to normal by the time of dis- liquid slug bait (Deadline, Pace National Corpo- charge. Convulsions continued for three days, ration) that contains 4 percent metaldehyde; in during which time an interictal electroencephalo- all, 18.9 grams or approximately 330 mg per kg of gram showed diffuse slowing with scattered epi- body weight was ingested. All other ingredients are leptiform discharges. The coma lasted for seven inert without known toxicity. days but tracheal intubation was prolonged to She soon had nausea and then vomiting. Two nine days due to general weakness and excessive hours after the ingestion she had the first of many secretions. generalized convulsions. Initially she was treated When communication became possible the pa- at a local hospital with gastric lavage, activated tient was noted to have pronounced memory charcoal and diazepam, but later that day was deficits, an exaggerated glabellar reflex and prom- transferred to Harborview Medical Center (Seat- inent snout and palmomental reflexes. Three tle) because of continuing convulsions, decreased months before this admission, the findings of a mental status and muscle spasms. By the time detailed neurologic examination (done during a transfer was completed the patient was comatose. hospital stay for a suicide attempt) had been On examination she was found to weigh 58 kg, entirely normal. her blood pressure was 130/90 mm of mercury, Her strength improved and administration of temperature 38.1°C and respirations 20 per min- anticonvulsant drugs was discontinued. Findings ute. An endotracheal tube was in place. Findings on lumbar puncture and contrast-enhanced cranial on general examination were unremarkable except computerized tomography were normal. Although for healed lacerations on her wrists and neck. On her mental status improved slowly, at best she had neurologic examination she was noted to be un- a poor recent and remote memory, flat affect and responsive to voice or painful stimuli. Pupils were pronounced latency of response. She was subse- reactive, eye movements were full on horizontal quently transferred to the psychiatric service. A repeat electroencephalogram was normal. Psycho- From the Department of Medicine, Division of Neurology ( Dr. Longstreth), and Division of Respiratory Diseases (Dr. Pierson), logical testing showed a verbal intelligence quo- Harborview Medical Center, Seattle. Submitted, revised, July 20, 1981. tient (IQ) of 100 and a performance IQ of 88 Reprint requests to: David J. Pierson, MD, Department of with a full scale IQ of 94; Halstan-Reitan battery Medicine, Harborview Medical Center, 325 Ninth Ave., Seattle, WA 98104. impairment index was 0.7. Primarily she had an

134 AUGUST 1982 * 137 * 2 CASE REPORTS adaptive problem-solving impairment and severe TABLE 1.-Metaldehyde Poisoning: Relation impairment of memory in both verbal and visual- Between Ingested Dose and Clinical Effects* spatial areas. The patient was discharged 51 days Dose Clinical Eflects after the attempted suicide. Traces (a few mg/kg) . . Salivation, facial flushing, One year after the poisoning, the patient re- fever, abdominal cramps, ported by telephone that her memory had returned nausea, vomiting almost to normal. Although still unemployed, she Up to 50 mg/kg ...... Drowsiness, tachycardia, had plans to spasms, irritability, salivation, eventually return to teaching. She abdominal cramps, facial declined a more formal follow-up evaluation. flushing, nausea 50-100 mg/kg ...... increased muscle tone Discussion Ataxia, 100-150 mg/kg ...... Convulsions, tremor, hyper- The first cases of metaldehyde poisoning oc- reflexia curred in the 1920's when metaldehyde was used 150-200 mg/kg ...... Muscle twitching Approximately as a combustible, that is, "meta-fuel" tablets.1-3 400 mg/kg ...... Coma, death The cases reported from Great Britain and con- tinental Europe were similar to the present case, *Adapted from Borbely.7 with vomiting, convulsions and coma being prom- inent features. It was not until the 1930's that by Ludin3 reviews the report of a person who inten- serendipity metaldehyde was discovered to be a tionally ingested approximately 2 grams of metal- potent molluscicide: "A lady who was using 'meta- dehyde to see if it had the same hypnotic effect fuel' to heat her curling tongs and threw the re- as paraldehyde. The acute symptoms were as mains out the window afterwards observed an described in the first two categories in the table assemblage of dead slugs."4 but he also reported a prolonged (weeks) yet There have been few reports of serious metal- reversible memory loss. dehyde poisoning with slug or snail baits in hu- The frequency of poisoning in the United States mans,5-6 and serious accidental poisonings with is unknown. From 1966 to 1980 the Environ- the meta-fuel tablets have been reduced since the mental Protection Agency (EPA) Pesticide and introduction in 1932 of a peppery coating on the Toxic Substance Branch found that 76 of 34,616 tablets. Intentional poisoning with the tablets has incidents reported involved metaldehyde, mostly continued mostly with suicide attempts, though in molluscicides, meta-f4el tablets not being avail- homicides have been reported as well.3 able in the United States.8 There were 52 cases of Borbely7 has reviewed 213 cases of metaldehyde metaldehyde poisoning in humans and 40 of 44 poisoning gleaned from the 15,000 cases in the home exposures involved children. Among the Swiss Toxicological Information Center between children, symptoms were minimal or absent and 1966 and 1969. All the cases of poisoning in there were no deaths. In three cases, including the children were accidental and were divided equally one reported here, the poisoning was severe. In between meta-fuel tablets and molluscicides. In one, nausea, vomiting and coma occurred without adults 20 of 24 cases were intentional and all other known details. In another, a 36-year-old involved the tablets. As would be expected with man ingested metaldehyde in an ethylene glycol the higher concentration of metaldehyde in the base. Vomiting, acidosis, tremulousness, convul- tablets, most of the cases with severe symptoms sions and coma ensued. The course was stormy involved tablets and only one involved a mollus- but not fatal. None of the exposures in humans cicide. In most children there were minimal symp- reported by the EPA is known to have resulted in toms and none died. Both fatalities in the series death.8 had intentionally taken a large number of the Of the approximately 187,000 cases reported to tablets. Although complete information was not the National Poison Center Network in 1979 from available in all cases, Borbely was able to establish all regions of the United States, 25 involved metal- a relationship between amount of metaldehyde dehyde.9 All 25 were children, 24 of whom were ingested and subsequent symptoms, as shown in treated at home, only one being seen in an emer- Table 1.7 gency room. In all, 21 of the 25 were asympto- Long-term sequelae from serious poisonings matic, 4 had mild symptoms and none died. are not well described. Our patient's memory prob- Interestingly, 80 percent of the reports came from lems that improved with time are of interest. Washington State. Unfortunately the reports to

THE WESTERN JOURNAL OF MEDICINE 135 CASE REPORTS the center are not complete and cases from Oregon salsolinol, an alkaloid shown to affect brain and California are not included. Given the density calcium metabolism and to be reversed by nalox- of slugs and snails-and hence molluscicide use- one hydrochloride.20 Whereas acetaldehyde com- on the West Coast, exposures are probably high petitively inhibits the aldehyde dehydrogenase throughout this area.'0 Most of the cases reported pathway, the alternate aldehyde reductase path- by the EPA came from California. Drs. K. Mattie way for breakdown is inhibited by barbiturates and A. Peoples, Worker Health and Safety Bureau and phenytoin.'0 In the treatment of convulsions of Pest Management, State Department of Food in metaldehyde poisoning, therefore, not only is and Agriculture, have monitored metaldehyde paraldehyde-a congener of metaldehyde-prob- poisoning in California and also report that inges- ably contraindicated, but so may be phenobarbital tion is common, almost always in children and and phenytoin. In our case high doses of the latter almost always asymptomatic (oral communica- drugs failed to control the patient's convulsions. tion, January 1981). Unfortunately neither acetaldehyde nor metal- How metaldehyde produces its toxic effects is dehyde levels were measured in our case. Assays unknown. Like paraldehyde it is a cyclic polymer for these substances are not readily available. An- of acetaldehyde, to which it may decompose in other way to monitor someone with known metal- the body.'0-'2 Evidence for such a breakdown is dehyde poisoning might be to measure ethanol minimal, though in two dogs with fatal metalde- levels, since ethanol would be formed from the hyde poisoning acetaldehyde was found in the acetaldehyde by the reverse alcohol dehydrogen- stomach contents,'3 and it is known to depolymer- ase-catalyzed reaction.'7 ize readily in an acid medium. The toxic effects of The mixed metabolic and respiratory alkalosis metaldehyde could be produced directly, through is of note. Although lactic acid formed during re- intermediate breakdown products or through ac- peated convulsions may have contributed to the etaldehyde, which is readily absorbed from the acidosis, metaldehyde itself may have been the gastrointestinal tract.'4 cause by mechanisms similar to those described in Although little is known about metaldehyde or paraldehyde overdoses.21 The respiratory alkalosis its intermediate breakdown products, a great deal may have been caused by acetaldehyde formed is known about acetaldehyde because of its sus- from metaldehyde. Injecting acetaldehyde intra- pected role in the toxicity of ethanol. The effects venously into humans, Asmussen and co-workers22 of metaldehyde poisoning (see Table 1) are sim- found it produced a pronounced increase in minute ilar to those seen with disulfiram (Antabuse) ventilation. reactions, which are presumed due in part to If one assumes the major toxicity from metal- increased acetaldehyde.15 Convulsions have been dehyde poisoning to be through acetaldehyde, are described with severe reactions, especially in an- there therapeutic implications? Numerous agents imals.'6 including D-penicillamine, N-acetylcysteine, thia- The toxic effects of acetaldehyde have been the mine and ascorbic acid have been shown in exper- subject of extensive study.'4"17"18 Central nervous imental animals to lower blood levels of acetalde- system toxicity may be mediated through compe- hyde given orally or induced by alcohol, that tition between acetaldehyde and biogenic alde- is, disulfiram reactions.'o72324 Acetaldehyde is hydes (breakdown products of the biogenic thought to condense nonenzymatically with sulf- amines) for aldehyde dehydrogenase with inhib- hydryl to form thiazolidine compounds, which are ition of oxidative pathways. Dopamine and sero- excreted in the urine. Thus the blood levels of tonin would be affected more than norepinephrine, acetaldehyde are lowered, and its pharmacologic which relies more on aldehyde reductase. The effects are reversed. Although N-acetylcysteine effects of the biogenic aldehydes are unknown, given by mouth is a suggested treatment for aceta- though they may be important in alterations of minophen poisonings,25 more data are needed be- consciousness during sleep.'9 Biogenic aldehydes fore it can be recommended for metaldehyde can also undergo condensation reactions with poisonings. other biogenic amines and aldehydes to produce This information suggests a rational approach alkaloids, similar to the process in poppies that to the treatment of metaldehyde poisoning. Usual leads to the formation of the alkaloid morphine. measures should be carried out, including gastric Such reactions are augmented by acetaldehyde, lavage with bicarbonate solution to decrease acidic which itself can condense with dopamine to form breakdown of metaldehyde to acetaldehyde, in

136 AUGUST 1982 * 137 * 2 CASE REPORTS addition to giving activated charcoal and cathartics. REFERENCES 1. Miller R: Poisoning by "meta fuel" tablets (metacetaldehyde). Flushing, nausea, vomiting, increased secretions Arch Dis Child 1928; 3:292-295 2. Lewis DR, Maldel CA, Drury J: Fatal poisoning by 'meta and decreased mental status should be anticipated fuel" tablets. Br Med J 1939 Jun 24; 1:1283-1284 and the trachea intubated early when airway 3. Ludin VM: Mord mit Meta? Schweiz Med Wochenschr 1958; pro- 88:381-384 tection or controlled ventilation is needed. Con- 4. Gimingham CT: Some recent contributions by English workers to the development of methods of insect control. Ann Appl Biol vulsions are common and should be treated with 1940; 27: 166-175 5. Spighel A, Alroy-Spighel M: Metaldehyde poisoning. Lancet diazepam given intravenously. Paraldehyde should 1958 Nov 8; 2:1017-1018 be avoided because it is a congener of metaldehyde. 6. Hancock BW, Martin JF, Ward JW, et al: Attempted suicide with a pesticide mixture. Resuscitation 1975; 44(4) :265-269 Although phenobarbital and phenytoin theoretical- 7. Borbely A: Beitrag zuir Frage der Metaldehydvergifttungen. Dissertion, Universitat Zurich. Zurich, Juris Druck uind Verlag, 1970 ly may have deleterious effects, convulsions must 8. Summary of Reported Pesticide Incidents Involving Metade- hyde-Pesticide Incident Mcnitcring System Report No. 285. Health be controlled. Dialysis is said not to be effective.7 Effects Branch, Hazard Evaluation Division Office of Pesticide Finally, if convulsions are uncontrolled and ele- Programs. Environmental Protection Agency, Mar 1980 9. National Poison Center Network: Computer System f. r Dcc- vated blood acetaldehyde levels can be docu- uimenting Data on Poisoni Exposures. Pittsburgh, PA, 1979 10. Arena JM: Poisoning: Toxicology, Symptoms, Treatments, mented, a trial of N-acetylcysteine or D-penicilla- 4th Ed. Springfield, III, Charles C Thomas, 1970, p 221, p 604 11. Dreisbach RH: Handbook of Poisoning: Prevention, Diag- mine should be considered. Although it rarely nosis and Treatment, 10th Ed. Los Altos, Calif. Lange Medical causes severe poisoning, metaldehyde can be fatal, Publications, 1980, pp 177-179 12. Moeschlin VS: Klinik und Therapie der Vergiftungen. Stutt- as reported in the literature, and can be associated gart, Georg Thieme Verlag, 1980, pp 284-285 13. Udall ND: The toxicity of the molluscicides metaldehyde and with considerable morbidity as in our case. methiocarb to dogs. Vet Rec 1973 Oct 13; 93:420-422 14. Akabane J: Aldehydes and related compounds, chap 19, in Radouco-Thomas C (Exec Ed): International Encyclopedia of Summary Pharmacology and Therapeutics-Section 20, Alcohols and Deriv- atives, Vol. 2. New York, Pergamon Press, 1970, pp 523-560 15. Ritchie JM: The aliphatic alcohols, chap. 18, In Goodman Metaldehyde poisoning has a long history in AG, Goodman LS, Gilman A (Eds): Goodman and Gilman's The to of Pharmacological Basis of Therapeutics, 6th Ed. New York, Mac- Europe due ingestion meta-fuel tablets, a millan Publishing, 1980, pp 387-388 combustible agent. In the United States, however, 16. Ezrielev GI: Acetaldehyde and alcoholism-Pharmacogen- esis of a disulfiram-alcohol reaction and its management by bind- exposure to metaldehyde occurs with ingestion of ing acetaldehyde with sodium metabisulfite. Sov Neurol Psychiatr 1973; 6:42-51 molluscicides (slug and snail baits) and serious 17. Lindros KO: Acetaldehyde-Its metabolism and role in the poisoning has only rarely been recorded. We de- actions of alcohol. Res Adv Alcohol Drug Prob 1978; 4:111-176 18. Weiner H: Acetaldehyde metabolism, chap 7, In Majchrowicz of E, Noble EP (Eds): Biochemistry and Pharmacology cf Ethanol, scribe the case a 32-year-old woman who inten- Vol 1. New York, Plenum Press, 1979, pp 125-144 tionally ingested a large quantity of liquid slug 19. Tipton KF. Houslay MD, Turner AJ: Metabolism of aIde- hydes in brain. Essays Neurochem Neuropharmacol 1977; 1:103- bait containing approximately 18 grams of metal- 138 20. Ross DH, Medina MA, Cardenas HL: Mcrphine and ethanol: dehyde. During a stormy two-week course, vomit- Selective depletion of regional brain calcium. Science 1974 Oct 4; 186(4158) :63-65 ing, increased salivation, convulsions and coma 21. Emmett M, Narins RG: Clinical use of the anion gap. Medi- cine (Baltimore), 1977 Jan; 56(l):38-54 developed. Recovery was complicated by pro- 22. Asmussen E, Hald J, Larsen V: The pharmacological actionl of acetaldehyde on the human organism. Acta Pharmacol 1948; longed memory and psychomotor dysfunction. 4: 311-320 Metaldehyde may produce its toxic effects 23. Sprince H, Parker CM, Smith GG, et al: Protective action through of ascorbic acid and sulfur compounds against acetaldehyde tox- a icity: Implications in alcoholism and smoking. Agents Actions breakdown to acetaldehyde, of which it is cyclic 1975 May; 5(2):164-173 polymer. Poisoning with this agent may thus be 24. Nagasawa HT, Goon DJW, DeMaster EG, et al: Lowering of ethanol-derived circulating blood acetaldehyde in rats by D- linked with the toxicity of ethanol and disulfiram penicillamine. Life Sci 1977 Jan 1; 20(1):187-194 25. Peterson RG, Rumack BH: Acetaminophen overdose: A high (Antabuse) reactions. index of suispicion. Top Emerg Med 1979; 1:43-49

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