- Email: [email protected]
GSH poisoning1
344 2. Kandil HH, Al-Ghanem MM, Sarwat MA, Al-Thallab FS. Henna (Lawsonia inermis Linn.) inducing haemolysis among G6PD-deficient newborns. A new clinical observation. Ann Trop Paediatr 1996;16:287–91. 3. Kök N, Ertekin MV, Ertekin V, Avcı B. Henna (Lawsonia inermis Linn.) induced haemolytic anemia in siblings Henna (Lawsonia inermis Linn.) induced haemolytic anemia. Int J Clin Pract 2004; 58:530 –2. 4. Sayil I. Review of suicide studies in Turkey. Crisis 1997;18:124–7. 5. Goren S, Gurkan F, Tirasci Y, Ozen S. Suicide in children and adolescents at a province in Turkey. Am J Forensic Med Pathol 2003;24:214–7. 6. Hashim M, Hamza YO, Yahia B, Khogali FM, Sulieman GI. Poisoning from henna dye and paraphenylenediamine mixtures in children in Khartoum. Ann Trop Paediatr 1992;12:3– 6. 7. Deveciogˇlu C, Katar S, Dogˇru Ö, Tas¸ MA. Henna-induced hemoltic anemia and acute renal failure. Turk J Pediatr 2001;43:65– 6. 8. Oztass MO, Onder M, Oztass P, Atahan C. Contact allergy to henna. J Eur Acad Dermatol 2001;15:140 –2.
e GSH POISONING1 e To the Editor: We wish to bring to the attention of providers in the United States, the potential toxicity of glyphosate-surfactant herbicidal (GSH) poisonings. In the United States in 2003, 4420 GSH exposures were reported to Poison Control Centers with 109 moderate to major effects and four deaths (1). With increasing use and prevalence of these agents due to heavy advertising and perceived safety, the number of poisonings is also likely to increase. We report the case of an intentional ingestion of Roundup® brand GSH. A 51-year-old man with a history of depression drank “4 –5 large gulps” of Roundup Weed and Grass Killer Super Concentrate® in a suicide attempt. This product contains 50.2% glyphosate isopropylamine and 15% polyoxyethyleneamine. He immediately began vomiting and complaining of oral pain. Three hours later, a friend brought him to the Emergency Department (ED) after calling the Poison Control Center for advice. On arrival, he was alert, but diaphoretic, and had profuse nausea, vomiting, and watery diarrhea. The initial vital signs were pulse of 72 beats/min, respiratory rate of 22 breaths/min, blood pressure of 159/74 mm Hg with a pulse oximetry reading of 92% on room air. Although he was complaining of oral pain, he was able to swallow
1 This correspondence was co-written by LCDR Michael J. Matteucci, MC, USNR, while a Fellow at UCSD Medical Center training in Medical Toxicology. The views expressed in the correspondence are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.
Letters to the Editor
without difficulty. He was given 50 grams of activated charcoal and normal saline fluid boluses. The vomiting ceased, but the diarrhea continued. The initial laboratory studies were significant for a white blood cell count of 25.5 cells/mm3, hemoglobin of 16.7 gm/dL, and a creatinine of 1.8 mg/dL (his baseline was 1.0). Approximately 24 h after the ingestion, the creatinine increased to 4.9 and urine output became negligible. The nephrology service was consulted and the patient underwent one 4-h course of hemodialysis after which he was started on furosemide. The urine output improved, as did the creatinine to 2.7. He was discharged to a psychiatric facility on hospital day 7. GSH is a widely used herbicide that is generally thought of as safe. In large ingestions, however, it can result in severe toxicity and death. The mechanism of herbicidal action of these products is for the surfactant to allow spread of the glyphosate over the leaf surface. The glyphosate is absorbed and blocks the shikimic acid pathway of plants, leading to their death (2). This shikimic acid pathway is not present in humans. Although glyphosate has been found to accumulate in the kidneys postmortem, most of its renal toxicity has been attributed to the surfactant component (3). Initial symptoms of GSH poisoning include gastrointestinal symptoms, including vomiting and diarrhea with associated massive fluid losses and hypotension, as well as mucosal irritation and erosions (4). Early mild hypoxemia and tachypnea are frequent with normal chest radiographic studies, but non-cardiac pulmonary edema has been reported with more severe ingestions (5). This is thought to be due to increased pulmonary vascular resistance caused by the surfactant component (6). Acute renal failure after GSH ingestion is rare (3 out of 131 cases in one series), but when present, had a 100% rate of mortality (7). Renal injury also may be delayed as it was in this case. Treatment of GSH exposure is generally supportive. Activated charcoal may be of use in binding some of the herbicide early after ingestion. Aggressive fluid rehydration is indicated for the severe gastrointestinal losses. Hemodialysis has not been proven to be of benefit for removal of GSH, but may be required for acute renal failure and electrolyte disbalances. After significant ingestions, mildly symptomatic patients should be observed for a minimum of 12 h before considering discharge (8). When fatalities due to GSH ingestion occur, they usually do so within 72 h of ingestion. Respiratory distress, pulmonary edema, renal failure or acidosis requiring hemodialysis, and hyperkalemia are poor prognostic signs. Roundup® and other brands of GSH are readily avail-
The Journal of Emergency Medicine
able in the United States. Ingestion of these agents can lead to significant toxicity. Michael J. Matteucci, MD Richard F. Clark, MD Division of Medical Toxicology University of California San Diego Medical Center San Diego, California doi:10.1016/j.jemermed.2005.06.004
REFERENCES 1. Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 annual report of the American Association of Poison Control Centers toxic exposure surveillance system. Am J Emerg Med 2004;22:335– 404. 2. Smith EA, Oehme FW. The biological activity of glyphosate to plants and animals: a literature review. Vet Hum Toxicol 1992;34: 531–3. 3. Sawada Y, Nagai Y, Ueyama M, et al. Probable toxicity of surfaceactive agent in commercial herbicide containing glyphosate. Lancet 1988;1:299. 4. Menkes DB, Temple WA, Edwards IR. Intentional self-poisoning with glyphosate-containing herbicides. Hum Exp Toxicol 1991;10: 103–7. 5. Talbot AR, Shiaw M-H, Huang J-S, et al. Acute poisoning with a glyphosate-surfactant herbicide (‘Round-up’): a review of 93 cases. Hum Exp Toxicol 1991;10:1– 8. 6. Tai T, Yamashita M, Wakimori H. Hemodynamic effects of Roundup, glyphosate and surfactant in dogs. Jpn J Toxicol 1990;3: 63– 8. 7. Lee H-L, Chen K-W, Chi C-H, et al. Clinical presentations and prognostic factors of a glyphosate-surfactant herbicide intoxication: a review of 131 cases. Acad Emerg Med 2000;7:906 –10. 8. Stella J, Ryan M. Glyphosate herbicide formulation: a potentially lethal ingestion. Emerg Med Australas 2004;16:235–9.
e TETANUS IN A FULLY IMMUNIZED CHILD e To the Editor: Tetanus is a devastating disease of muscle spasm and autonomic instability with a high mortality. Despite being easily preventable with a highly effective vaccine, tetanus remains a significant source of morbidity and mortality worldwide (1,2). Although the majority of tetanus cases occur in third-world countries, there are still significant numbers of cases occurring in countries such as the United States, where preventive immunization is easily accessible. Tetanus prevention is addressed daily in the Emergency Department (ED) as part of wound care, but acute tetanus is rarely seen. A previously healthy 7-year-old girl was admitted to the hospital after experiencing what was described as an epileptic fit. Before the fit, the patient had flu-like symptoms for 5 days. Her family reported that she had a finger cut on her thumb 10 days before the episode and that she had no history of recurrent infections. Physical exami-
345
nation showed that the patient had a low-grade fever (37.7°C). The blood pressure was 110/70 mm Hg and pulse rate was 104 beats/min. She had trismus, the characteristic facial expression and spasms of tetanus accentuated by external stimuli. The local wound scar due to a knife wound laceration of the thumb was seen on examination. She was alert and coherent, and all other physical and neurological findings were normal. Laboratory studies showed a leukocyte count of 13.500 ⫻ 106/L and a hemoglobin concentration of 12.6 g/L. Serum immunoglobulin values were normal, as were the electroencephalographic findings and computed tomography scans of the brain. Examination of cerebrospinal fluid showed no abnormalities. Phenytoin treatment was started on the first day of admission to hospital. During the following day, however, the patient’s attempts to talk or to get up triggered attacks of risus sardonicus, opisthotonus and trismus. Tetanus was diagnosed clinically, and the patient was treated with 500 U of human tetanus immunoglobulin. Treatment with intravenous metronidazole (250 mg thrice daily) was begun, and the patient was transferred to the intensive care unit. The generalized severe muscular spasms continued, and the patient was sedated. She was treated with intravenous diazepam (2 mg/kg/day intravenously in six divided doses). During the first 8 days in the hospital, repeated attempts to stop the diazepam resulted in recurrence of spasms. Thereafter, we were able to withdraw diazepam. The patient’s immunization record showed that she had been immunized against tetanus according to the recommendations of the Turkey Ministry of Health. After the recent acquired injury, however, she had not been given tetanus booster doses before the present hospital admission. She received active antitetanus vaccination shortly before she was discharged from the hospital. The antibody level of 0.17 IU/mL was found in our patient after vaccination. The development of tetanus despite full immunization is extremely rare. It is estimated at 4 per 100 million immunocompetent vaccinated subjects. There are case reports of tetanus in immunocompetent individuals with “protective” antibody levels. Unfortunately, antitoxin antibody levels are not likely to be available at the time when management decisions must be made. The mechanism of immunization failure is unclear. Theories include a burden of toxin that overwhelms the host immune defenses, antigenic variability between toxin and toxoid, and selective suppression of the immune response (3,4). Fortunately, the presentation of tetanus was so characteristic that a presumptive diagnosis could be made in our case. Even with appropriate immunization and boosters given for wound management, it appears that there will still be cases of tetanus, as described above. The diagnosis is based on clinical recognition,
e GSH POISONING1 e To the Editor: We wish to bring to the attention of providers in the United States, the potential toxicity of glyphosate-surfactant herbicidal (GSH) poisonings. In the United States in 2003, 4420 GSH exposures were reported to Poison Control Centers with 109 moderate to major effects and four deaths (1). With increasing use and prevalence of these agents due to heavy advertising and perceived safety, the number of poisonings is also likely to increase. We report the case of an intentional ingestion of Roundup® brand GSH. A 51-year-old man with a history of depression drank “4 –5 large gulps” of Roundup Weed and Grass Killer Super Concentrate® in a suicide attempt. This product contains 50.2% glyphosate isopropylamine and 15% polyoxyethyleneamine. He immediately began vomiting and complaining of oral pain. Three hours later, a friend brought him to the Emergency Department (ED) after calling the Poison Control Center for advice. On arrival, he was alert, but diaphoretic, and had profuse nausea, vomiting, and watery diarrhea. The initial vital signs were pulse of 72 beats/min, respiratory rate of 22 breaths/min, blood pressure of 159/74 mm Hg with a pulse oximetry reading of 92% on room air. Although he was complaining of oral pain, he was able to swallow
1 This correspondence was co-written by LCDR Michael J. Matteucci, MC, USNR, while a Fellow at UCSD Medical Center training in Medical Toxicology. The views expressed in the correspondence are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.
Letters to the Editor
without difficulty. He was given 50 grams of activated charcoal and normal saline fluid boluses. The vomiting ceased, but the diarrhea continued. The initial laboratory studies were significant for a white blood cell count of 25.5 cells/mm3, hemoglobin of 16.7 gm/dL, and a creatinine of 1.8 mg/dL (his baseline was 1.0). Approximately 24 h after the ingestion, the creatinine increased to 4.9 and urine output became negligible. The nephrology service was consulted and the patient underwent one 4-h course of hemodialysis after which he was started on furosemide. The urine output improved, as did the creatinine to 2.7. He was discharged to a psychiatric facility on hospital day 7. GSH is a widely used herbicide that is generally thought of as safe. In large ingestions, however, it can result in severe toxicity and death. The mechanism of herbicidal action of these products is for the surfactant to allow spread of the glyphosate over the leaf surface. The glyphosate is absorbed and blocks the shikimic acid pathway of plants, leading to their death (2). This shikimic acid pathway is not present in humans. Although glyphosate has been found to accumulate in the kidneys postmortem, most of its renal toxicity has been attributed to the surfactant component (3). Initial symptoms of GSH poisoning include gastrointestinal symptoms, including vomiting and diarrhea with associated massive fluid losses and hypotension, as well as mucosal irritation and erosions (4). Early mild hypoxemia and tachypnea are frequent with normal chest radiographic studies, but non-cardiac pulmonary edema has been reported with more severe ingestions (5). This is thought to be due to increased pulmonary vascular resistance caused by the surfactant component (6). Acute renal failure after GSH ingestion is rare (3 out of 131 cases in one series), but when present, had a 100% rate of mortality (7). Renal injury also may be delayed as it was in this case. Treatment of GSH exposure is generally supportive. Activated charcoal may be of use in binding some of the herbicide early after ingestion. Aggressive fluid rehydration is indicated for the severe gastrointestinal losses. Hemodialysis has not been proven to be of benefit for removal of GSH, but may be required for acute renal failure and electrolyte disbalances. After significant ingestions, mildly symptomatic patients should be observed for a minimum of 12 h before considering discharge (8). When fatalities due to GSH ingestion occur, they usually do so within 72 h of ingestion. Respiratory distress, pulmonary edema, renal failure or acidosis requiring hemodialysis, and hyperkalemia are poor prognostic signs. Roundup® and other brands of GSH are readily avail-
The Journal of Emergency Medicine
able in the United States. Ingestion of these agents can lead to significant toxicity. Michael J. Matteucci, MD Richard F. Clark, MD Division of Medical Toxicology University of California San Diego Medical Center San Diego, California doi:10.1016/j.jemermed.2005.06.004
REFERENCES 1. Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 annual report of the American Association of Poison Control Centers toxic exposure surveillance system. Am J Emerg Med 2004;22:335– 404. 2. Smith EA, Oehme FW. The biological activity of glyphosate to plants and animals: a literature review. Vet Hum Toxicol 1992;34: 531–3. 3. Sawada Y, Nagai Y, Ueyama M, et al. Probable toxicity of surfaceactive agent in commercial herbicide containing glyphosate. Lancet 1988;1:299. 4. Menkes DB, Temple WA, Edwards IR. Intentional self-poisoning with glyphosate-containing herbicides. Hum Exp Toxicol 1991;10: 103–7. 5. Talbot AR, Shiaw M-H, Huang J-S, et al. Acute poisoning with a glyphosate-surfactant herbicide (‘Round-up’): a review of 93 cases. Hum Exp Toxicol 1991;10:1– 8. 6. Tai T, Yamashita M, Wakimori H. Hemodynamic effects of Roundup, glyphosate and surfactant in dogs. Jpn J Toxicol 1990;3: 63– 8. 7. Lee H-L, Chen K-W, Chi C-H, et al. Clinical presentations and prognostic factors of a glyphosate-surfactant herbicide intoxication: a review of 131 cases. Acad Emerg Med 2000;7:906 –10. 8. Stella J, Ryan M. Glyphosate herbicide formulation: a potentially lethal ingestion. Emerg Med Australas 2004;16:235–9.
e TETANUS IN A FULLY IMMUNIZED CHILD e To the Editor: Tetanus is a devastating disease of muscle spasm and autonomic instability with a high mortality. Despite being easily preventable with a highly effective vaccine, tetanus remains a significant source of morbidity and mortality worldwide (1,2). Although the majority of tetanus cases occur in third-world countries, there are still significant numbers of cases occurring in countries such as the United States, where preventive immunization is easily accessible. Tetanus prevention is addressed daily in the Emergency Department (ED) as part of wound care, but acute tetanus is rarely seen. A previously healthy 7-year-old girl was admitted to the hospital after experiencing what was described as an epileptic fit. Before the fit, the patient had flu-like symptoms for 5 days. Her family reported that she had a finger cut on her thumb 10 days before the episode and that she had no history of recurrent infections. Physical exami-
345
nation showed that the patient had a low-grade fever (37.7°C). The blood pressure was 110/70 mm Hg and pulse rate was 104 beats/min. She had trismus, the characteristic facial expression and spasms of tetanus accentuated by external stimuli. The local wound scar due to a knife wound laceration of the thumb was seen on examination. She was alert and coherent, and all other physical and neurological findings were normal. Laboratory studies showed a leukocyte count of 13.500 ⫻ 106/L and a hemoglobin concentration of 12.6 g/L. Serum immunoglobulin values were normal, as were the electroencephalographic findings and computed tomography scans of the brain. Examination of cerebrospinal fluid showed no abnormalities. Phenytoin treatment was started on the first day of admission to hospital. During the following day, however, the patient’s attempts to talk or to get up triggered attacks of risus sardonicus, opisthotonus and trismus. Tetanus was diagnosed clinically, and the patient was treated with 500 U of human tetanus immunoglobulin. Treatment with intravenous metronidazole (250 mg thrice daily) was begun, and the patient was transferred to the intensive care unit. The generalized severe muscular spasms continued, and the patient was sedated. She was treated with intravenous diazepam (2 mg/kg/day intravenously in six divided doses). During the first 8 days in the hospital, repeated attempts to stop the diazepam resulted in recurrence of spasms. Thereafter, we were able to withdraw diazepam. The patient’s immunization record showed that she had been immunized against tetanus according to the recommendations of the Turkey Ministry of Health. After the recent acquired injury, however, she had not been given tetanus booster doses before the present hospital admission. She received active antitetanus vaccination shortly before she was discharged from the hospital. The antibody level of 0.17 IU/mL was found in our patient after vaccination. The development of tetanus despite full immunization is extremely rare. It is estimated at 4 per 100 million immunocompetent vaccinated subjects. There are case reports of tetanus in immunocompetent individuals with “protective” antibody levels. Unfortunately, antitoxin antibody levels are not likely to be available at the time when management decisions must be made. The mechanism of immunization failure is unclear. Theories include a burden of toxin that overwhelms the host immune defenses, antigenic variability between toxin and toxoid, and selective suppression of the immune response (3,4). Fortunately, the presentation of tetanus was so characteristic that a presumptive diagnosis could be made in our case. Even with appropriate immunization and boosters given for wound management, it appears that there will still be cases of tetanus, as described above. The diagnosis is based on clinical recognition,