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Seizures Caused by Ingestion of Composition C-4
CASE REPORT
eizures Caused by Ingestion of Composition C-4 From the Emergency Medicine Department, Naval Hospital, Camp Pendleton, California*; and the Clinical Investigation Department, Naval Medical Center, 5an Diego, California.~
Receivedfor publication January 23, 1995. Revision received June 12, I995. Accepted for publication June 30, 1995. The chief of the Bureau of Medicine and Surgery, Navy Department, Washington DC, Clinical Investigation Program, sponsored this report, 84-16-1968-515, as required by Health Science Education aand Training Command Instruction 6000.41A. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States government. Copyright © by the American College of Emergency Physicians.
Beverly HarrelI-Bruder, MD** Keith L Hutchins, BS, PA-C**
Composition C-4 (C-4)is a plastic explosive widely used in both military and civilian settings. Ingestion of the active ingredient, RDX (cyclonite), can cause generalized seizures. Accidental and intentional C-4 (RDX)intoxications have occurred during manufacture or in wartime. In the literature the intentional ingestion of C-4 has been reported but not verified. We present a case of intentional C-4 abuse. [HarrelI-Bruder B, Hutchins KL: Seizures caused by ingestion of composition C-4. Ann EmergMed December 1995;26:746-748.]
INTRODUCTION RDX (cyclotrimethylenetrinitramine [cyclonite]), a highly explosive compound, is the main constituent (91%) of the plastic explosive composition C-4.1 When ingested or inhaled in sufficient quantities (calculated dose of. 1 mg RDX/kg/day; no 50% lethal dose has been calculated for the plasticized version of the compound), dramatic clinical symptoms develop rapidly. 2,3 Generalired seizures, gross hematuria, nausea and vomiting, muscle twitching, and changes in mentation are frequently observed. <5 We present a case of generalized seizures following C-4 ingestion.
CASE REPORT A 20-year-old active duty military man was brought to the emergency department by ambulance after sustaining a witnessed generalized tonic-clonic seizure that lasted less than 5 minutes. On arrival, the patient appeared confused and kept referring to his watch to recall the time and date. He denied any recall of the seizure or the events of the preceding 6 hours. The patient's supervisors reported that he had complained of a headache that morning. He had been found around the same time to be chewing on a piece (size undetermined) of C-4 explosive, which he reportedly refused to stop chewing.
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ANNALS OF EMERGENCY MEDICINE
26:6 DECEMBER
1995
C O M P O S I T I O N C-4 Harrell-Bruder & Hutchins
m
On presentation, blood pressure was 130/65 mm Hg, respirations 16, pulse 120, and oral temperature 36.6°C. The findings of the initial physical and neurologic examinations were normal, except for the patient's postictal state. The results of a metabolic panel (sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, creatinine, and glucose) were within normal limits. Assay of arterial blood gases on room air revealed a pH of 7.32, PO2 of 94 mm Hg, and Pco 2 of 42 mm Hg. The WBC count was 14,500/InL with 87% neutrophils, hematocrit and hemoglobin were normal, mean corpuscular volume was 90.3 l~m3, and the platelet count was 348,000/1~L. Urinalysis revealed specific gravity of 1.030, pH of 5.0, 6 to 10 RBCs, and otherwise normal findings. Results of a screen for marijuana, cocaine, opiates, benzodiazepines, and amphetamines were negative. Findings of noncontrast computed tomography of the head were normal. Approximately 2 hours after arrival, the patient had a second generalized tonic-clonic seizure. It lasted approximately 2 minutes; the patient had urinary incontinence, and the postictal state lasted approximately 30 minutes. He was treated with 30 g of activated charcoal administered through a nasogastric tube, IV lorazepam 1 mg, and a loading dose of phenytoin 400 rag. The findings of a lumbar puncture were normal. The patient was admitted to the ICU, and phenytoin administration was continued. The findings of serial neurologic examinations were normal, with the exception of brisk deep-tendon reflexes. Two EEGs were performed, one on hospital day 2 and the second after sleep deprivation on hospital day 3; the findings of both were normal. Psychiatric evaluation revealed a borderline-personality disorder. The patient was able to recall events leading to his hospitalization but could not explain why he had chewed C-4. He was transferred to a general medicine ward on hospital day 1, with continued administration of phenytoin. He had no further seizures or symptoms in 30 days of follow-up. The patient was continued on phenyloin for a total of 10 days. DISCUSSION
Composition C-4 is a plasticized explosive containing RDX in 91% concentration. It also contains small amounts of polyisobutylene (2.1%), motor oil (1.6%), and di-(2-ethyl-hexyl) sebacate (5.3%). 6 C-4 was used mainly during the Vietnam War in demolition blocks, and it is still used for demolition and in flares in both civilian and military settings. It was common knowledge during the Vietnam War that ingestion of small amounts
DECEMBER t995
26:6
ANNALS OF EMERGENCY MEDICINE
of C-4 would produce a high similar to that of ethanol, r Several serious intoxications from this agent were noted during the Vietnam War. t,5,6 Such intoxications have also been reported in civilians in the United States, particularly in factory workers who handle and package this explosive, s The toxic effects of C-4 on the central nervous system (CNS) were first reported in workers in whom seizures developed when they handled and packed the material. These seizures were thought to be a result of inhalation of the chemical dust. s Ingestion of C-4 was identified during the Vietnam War as the cause of a toxic encephalopathy on the basis of presenting symptoms and EEG changes associated with generalized seizures. 5 After composition C-4 is ingested or inhaled, its breakdown products cause CNS (most common), renal, and gastrointestinal toxicitT~r CNS signs (in order of presentation) are confusion, marked hyperirritability, myoclonic seizures, and severe generalized tonic-ctonic seizures with subsequent amnesia. 5 Renal and hepatic involvement are rare, consisting of oliguria, gross hematuria, proteinuria, and increased blood urea nitrogen. Increased aminotransferase and serum bilirubin levels have also been reported. 9 Toxic CNS effects, both clinically and electroencephalographically, generally resolve within weeks or, occasionally, several months. 5,6 Review of the literature showed no reported seizure activity after 3 days but did reveal that RDX has been reported to be present in stool and blood as long as 144 hours after ingestion) Management of C-4 intoxication consists of airway maintenance, early gastric lavage 3,r, seizure control with anticon~m]sants, monitoring of urine output to detect and prevent acute renal insufficiency, and maintenance of normal fluid and electrolyte balances. Because of its chemical structure and solubility characteristics, RDX would not be removed by peritoneal dialysis or hemodialysis in significant quantities. 5,6,to, 1s SUMMARY
Composition C-4 is a soft, puttylike plastic explosive widely used in military and civilian settings. When ingested, C-4 may cause CNS, renal, and gastrointestinal toxicity. These effects appear to be reversible, and acute ingestion may be handled with supportive measures. Seizure control can be carried out with standard anticonvulsant therapy: Steps to detect C-4 toxicity should be part of the diagnostic workup for the sudden onset of multiple generalized seizures in previously healthy patients with possible exposure, especially in a military or construction, environment.
747
COMPOSITION C-4 Harrell-Brt¢der & Hutchins
REFERENCES 1. Stone w J, Paletta TL, Heiman EM, et al: Toxic effects following ingestion of C-4 plastic explosive. Arch Intern Med 1989;124:726-730. 2. Burdette LJ, Cook LL, Dyer RS: Convulsant properties of cyclotrimethylenednitramine {RDXI: Spontaneous,audiogenic, and amygdaleid kindled seizure activity. ToxicolApplPharmacol 1988;92:436-444. 3. Woody RC, KearneGL, Brewster MA, et ah The neurotoxicity of cyclotdmethylenetrinitramine (RDX) in a child: A clinical and pharmocokinetics evaluation. J Toxicol Clin Toxicol 1986;24:305319. 4. Kaplan AS, Berghout CF, PeczenikA: Human intoxication from RDX; Arch Environ Health 1965;10:877-883.
Reprint no. 47/1/68847 Address for reprints: ENS Keith L Hutchins, MSC, USN Clinical Investigation Department Naval Medical Center San Diego, Oalifornia 92134-5000 619-532-8134/8140 Fax 619-532-8137
5. Ketel WB, HughesJR: Toxic encephalopathy with seizuressecondary to ingestion of composition C-4. Neurology 1972;22:871-876. 9. HorlanderAI, Oolbach EM: Composition 0-4 induced seizures:A repert of five cases. Milit Meal 1969;134:1529-1530. 7. Von Ottengen WF, Donahue DD, Yagoda H, eta[: Toxicity and potential dangers of cyclotrimethylenetrinitramine {BDX). J Industrial Hyg Texico11949;31:21-31. 8. Hathaway JA, Buck CR: Absence of health hazardsassociated with RDX manufacture and use. J Occup Meal 1977;19:269-272. 9. Levine BS, Furedi EM, Gordon DE, et al: Toxic interactions of the munitions compoundsTNT and RDX in F344 rats. FundamAppl Toxico11990;15:373-380. 10. Goldberg DJ, Nathwani D, Hamlet N, et al: RDX intoxication causing seizures and a wide spread petechial rash mimicking meningococcaemia.J R Soc Med1982;85:181. 11. Schneider NR, Bradley SL, Anderson ME: The distribution and metabolism of cyclotrimethylene-trinitramine (RDX)in the rat after subchronic administration. Toxico/ApplPharmaco/ 1978;46:163-172.
748
ANNALS OF EMERGENCY MEDLCINE 26:6
DECEMBER 1995
eizures Caused by Ingestion of Composition C-4 From the Emergency Medicine Department, Naval Hospital, Camp Pendleton, California*; and the Clinical Investigation Department, Naval Medical Center, 5an Diego, California.~
Receivedfor publication January 23, 1995. Revision received June 12, I995. Accepted for publication June 30, 1995. The chief of the Bureau of Medicine and Surgery, Navy Department, Washington DC, Clinical Investigation Program, sponsored this report, 84-16-1968-515, as required by Health Science Education aand Training Command Instruction 6000.41A. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States government. Copyright © by the American College of Emergency Physicians.
Beverly HarrelI-Bruder, MD** Keith L Hutchins, BS, PA-C**
Composition C-4 (C-4)is a plastic explosive widely used in both military and civilian settings. Ingestion of the active ingredient, RDX (cyclonite), can cause generalized seizures. Accidental and intentional C-4 (RDX)intoxications have occurred during manufacture or in wartime. In the literature the intentional ingestion of C-4 has been reported but not verified. We present a case of intentional C-4 abuse. [HarrelI-Bruder B, Hutchins KL: Seizures caused by ingestion of composition C-4. Ann EmergMed December 1995;26:746-748.]
INTRODUCTION RDX (cyclotrimethylenetrinitramine [cyclonite]), a highly explosive compound, is the main constituent (91%) of the plastic explosive composition C-4.1 When ingested or inhaled in sufficient quantities (calculated dose of. 1 mg RDX/kg/day; no 50% lethal dose has been calculated for the plasticized version of the compound), dramatic clinical symptoms develop rapidly. 2,3 Generalired seizures, gross hematuria, nausea and vomiting, muscle twitching, and changes in mentation are frequently observed. <5 We present a case of generalized seizures following C-4 ingestion.
CASE REPORT A 20-year-old active duty military man was brought to the emergency department by ambulance after sustaining a witnessed generalized tonic-clonic seizure that lasted less than 5 minutes. On arrival, the patient appeared confused and kept referring to his watch to recall the time and date. He denied any recall of the seizure or the events of the preceding 6 hours. The patient's supervisors reported that he had complained of a headache that morning. He had been found around the same time to be chewing on a piece (size undetermined) of C-4 explosive, which he reportedly refused to stop chewing.
746
ANNALS OF EMERGENCY MEDICINE
26:6 DECEMBER
1995
C O M P O S I T I O N C-4 Harrell-Bruder & Hutchins
m
On presentation, blood pressure was 130/65 mm Hg, respirations 16, pulse 120, and oral temperature 36.6°C. The findings of the initial physical and neurologic examinations were normal, except for the patient's postictal state. The results of a metabolic panel (sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, creatinine, and glucose) were within normal limits. Assay of arterial blood gases on room air revealed a pH of 7.32, PO2 of 94 mm Hg, and Pco 2 of 42 mm Hg. The WBC count was 14,500/InL with 87% neutrophils, hematocrit and hemoglobin were normal, mean corpuscular volume was 90.3 l~m3, and the platelet count was 348,000/1~L. Urinalysis revealed specific gravity of 1.030, pH of 5.0, 6 to 10 RBCs, and otherwise normal findings. Results of a screen for marijuana, cocaine, opiates, benzodiazepines, and amphetamines were negative. Findings of noncontrast computed tomography of the head were normal. Approximately 2 hours after arrival, the patient had a second generalized tonic-clonic seizure. It lasted approximately 2 minutes; the patient had urinary incontinence, and the postictal state lasted approximately 30 minutes. He was treated with 30 g of activated charcoal administered through a nasogastric tube, IV lorazepam 1 mg, and a loading dose of phenytoin 400 rag. The findings of a lumbar puncture were normal. The patient was admitted to the ICU, and phenytoin administration was continued. The findings of serial neurologic examinations were normal, with the exception of brisk deep-tendon reflexes. Two EEGs were performed, one on hospital day 2 and the second after sleep deprivation on hospital day 3; the findings of both were normal. Psychiatric evaluation revealed a borderline-personality disorder. The patient was able to recall events leading to his hospitalization but could not explain why he had chewed C-4. He was transferred to a general medicine ward on hospital day 1, with continued administration of phenytoin. He had no further seizures or symptoms in 30 days of follow-up. The patient was continued on phenyloin for a total of 10 days. DISCUSSION
Composition C-4 is a plasticized explosive containing RDX in 91% concentration. It also contains small amounts of polyisobutylene (2.1%), motor oil (1.6%), and di-(2-ethyl-hexyl) sebacate (5.3%). 6 C-4 was used mainly during the Vietnam War in demolition blocks, and it is still used for demolition and in flares in both civilian and military settings. It was common knowledge during the Vietnam War that ingestion of small amounts
DECEMBER t995
26:6
ANNALS OF EMERGENCY MEDICINE
of C-4 would produce a high similar to that of ethanol, r Several serious intoxications from this agent were noted during the Vietnam War. t,5,6 Such intoxications have also been reported in civilians in the United States, particularly in factory workers who handle and package this explosive, s The toxic effects of C-4 on the central nervous system (CNS) were first reported in workers in whom seizures developed when they handled and packed the material. These seizures were thought to be a result of inhalation of the chemical dust. s Ingestion of C-4 was identified during the Vietnam War as the cause of a toxic encephalopathy on the basis of presenting symptoms and EEG changes associated with generalized seizures. 5 After composition C-4 is ingested or inhaled, its breakdown products cause CNS (most common), renal, and gastrointestinal toxicitT~r CNS signs (in order of presentation) are confusion, marked hyperirritability, myoclonic seizures, and severe generalized tonic-ctonic seizures with subsequent amnesia. 5 Renal and hepatic involvement are rare, consisting of oliguria, gross hematuria, proteinuria, and increased blood urea nitrogen. Increased aminotransferase and serum bilirubin levels have also been reported. 9 Toxic CNS effects, both clinically and electroencephalographically, generally resolve within weeks or, occasionally, several months. 5,6 Review of the literature showed no reported seizure activity after 3 days but did reveal that RDX has been reported to be present in stool and blood as long as 144 hours after ingestion) Management of C-4 intoxication consists of airway maintenance, early gastric lavage 3,r, seizure control with anticon~m]sants, monitoring of urine output to detect and prevent acute renal insufficiency, and maintenance of normal fluid and electrolyte balances. Because of its chemical structure and solubility characteristics, RDX would not be removed by peritoneal dialysis or hemodialysis in significant quantities. 5,6,to, 1s SUMMARY
Composition C-4 is a soft, puttylike plastic explosive widely used in military and civilian settings. When ingested, C-4 may cause CNS, renal, and gastrointestinal toxicity. These effects appear to be reversible, and acute ingestion may be handled with supportive measures. Seizure control can be carried out with standard anticonvulsant therapy: Steps to detect C-4 toxicity should be part of the diagnostic workup for the sudden onset of multiple generalized seizures in previously healthy patients with possible exposure, especially in a military or construction, environment.
747
COMPOSITION C-4 Harrell-Brt¢der & Hutchins
REFERENCES 1. Stone w J, Paletta TL, Heiman EM, et al: Toxic effects following ingestion of C-4 plastic explosive. Arch Intern Med 1989;124:726-730. 2. Burdette LJ, Cook LL, Dyer RS: Convulsant properties of cyclotrimethylenednitramine {RDXI: Spontaneous,audiogenic, and amygdaleid kindled seizure activity. ToxicolApplPharmacol 1988;92:436-444. 3. Woody RC, KearneGL, Brewster MA, et ah The neurotoxicity of cyclotdmethylenetrinitramine (RDX) in a child: A clinical and pharmocokinetics evaluation. J Toxicol Clin Toxicol 1986;24:305319. 4. Kaplan AS, Berghout CF, PeczenikA: Human intoxication from RDX; Arch Environ Health 1965;10:877-883.
Reprint no. 47/1/68847 Address for reprints: ENS Keith L Hutchins, MSC, USN Clinical Investigation Department Naval Medical Center San Diego, Oalifornia 92134-5000 619-532-8134/8140 Fax 619-532-8137
5. Ketel WB, HughesJR: Toxic encephalopathy with seizuressecondary to ingestion of composition C-4. Neurology 1972;22:871-876. 9. HorlanderAI, Oolbach EM: Composition 0-4 induced seizures:A repert of five cases. Milit Meal 1969;134:1529-1530. 7. Von Ottengen WF, Donahue DD, Yagoda H, eta[: Toxicity and potential dangers of cyclotrimethylenetrinitramine {BDX). J Industrial Hyg Texico11949;31:21-31. 8. Hathaway JA, Buck CR: Absence of health hazardsassociated with RDX manufacture and use. J Occup Meal 1977;19:269-272. 9. Levine BS, Furedi EM, Gordon DE, et al: Toxic interactions of the munitions compoundsTNT and RDX in F344 rats. FundamAppl Toxico11990;15:373-380. 10. Goldberg DJ, Nathwani D, Hamlet N, et al: RDX intoxication causing seizures and a wide spread petechial rash mimicking meningococcaemia.J R Soc Med1982;85:181. 11. Schneider NR, Bradley SL, Anderson ME: The distribution and metabolism of cyclotrimethylene-trinitramine (RDX)in the rat after subchronic administration. Toxico/ApplPharmaco/ 1978;46:163-172.
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ANNALS OF EMERGENCY MEDLCINE 26:6
DECEMBER 1995