Journal of Toxicology CLINICAL TOXICOLOGY Vol. 42, No. 3, pp. 299–303, 2004
CASE REPORT
Toxicity Following Unintentional DDT Ingestion D. Niyazi Ozucelik, M.D.,1 Ozgur Karcioglu, M.D.,2,* Hakan Topacoglu, M.D.,2 and John R. Fowler, M.D.2 1
Department of Emergency Medicine, School of Medicine, Hacettepe University, Ankara, Turkey 2 Department of Emergency Medicine, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey
ABSTRACT Introduction: Dichlorodiphenyltrichloroethane (DDT) ingestion is an uncommon cause of poisoning worldwide. To date, no cases of renal impairment after oral intake of DDT in humans have been reported. We describe the clinical course and management of two patients presenting after DDT ingestion, one of whom developed acute oliguric renal failure. Case Report: A father and son mistook DDT powder for flour while preparing fish for a meal, and after eating they developed symptoms compatible with acute organochlorine insecticide poisoning. Both were intubated endotracheally due to recurrent convulsions and loss of consciousness followed by admission to the intensive care unit. Both cases developed severe metabolic acidosis. Acute oliguric renal failure (ARF) was diagnosed in the son in the second day, with a blood urea nitrogen level of 47 mg/dl and creatinine 6.4 mg/dl. Urinalysis disclosed abundant RBCs on the third day. Vigorous fluid resuscitation and strict monitoring helped reverse its clinical course by the tenth day. Both patients recovered within two weeks and were discharged without sequelae. Conclusion: Clinicians should not overlook the possibility of DDT poisoning in the differential diagnosis of acute renal failure and seizures. More strict measures should be taken to prohibit misidentification of DDT and similar products, particularly in the developing world. Key Words:
DDT; Poisoning; Renal failure; Organochlorine pesticides.
*Correspondence: Ozgur Karcioglu, M.D., Dept. of Emergency Medicine, Dokuz Eylul University School of Medicine, Inciralti, Izmir 35340, Turkey; Fax: + 90-232-2590541; E-mail:
[email protected]. 299 DOI: 10.1081/CLT-120037432 Copyright D 2004 by Marcel Dekker, Inc.
0731-3810 (Print); 1097-9875 (Online) www.dekker.com
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UNINTENTIONAL INGESTION IN TWO PATIENTS
INTRODUCTION Chlorinated hydrocarbon pesticides and insecticides are known to persist in their active form in the environment after its agricultural use. Dichlorodiphenyltrichloroethane (DDT) is an organochlorine pesticide and also one of the most commonly utilized pesticides in the twentieth century. Use has declined sharply worldwide after production and use of DDT was prohibited in the United States in 1973 (1 –3). Domestic use of DDT is illegal in Turkey but is still available on the black market. DDT rarely causes significant intoxications in human beings. Availability in various forms—dermal, ocular, oral, and inhalational absorbability—also enhance toxicity (4). The severity of the course depends on molecular size and CNS effects (5). Factors of the exposure such as the route, duration, and amount of the offending agent determine the severity of clinical findings (3). Accidental intoxications occur most commonly in children whereas adults generally ingest intentionally (5). The lethal dose in an adult is estimated to be 30 g (6). Estimated oral DDT doses as low as 10 –16 mg/kg have caused seizures (4,7). Fatality usually occurs within 4 to 8 h because of respiratory failure and the sequelae of metabolic acidosis secondary to prolonged seizure activity (4). No specific antidote has been established, though benzodiazepines are beneficial in the management of seizure activity. The medical literature cites only a few cases of DDT poisoning with significant clinical courses (8). We report two cases of DDT poisoning occurring following the unintentional ingestion of a powder containing DDT.
Table 1.
BUN (mg/dl) Creatinine (mg/dl) Na (mEq/l) K (mEq/l) AST (U/l) ALT (U/l) Hemoglobin Hematocrit (%)
A 47-year-old man brought some fish home from the local market and searched for flour with which to fry them for himself and his 15-year-old son. He found a light whitish-gray powder in a jar on the kitchen shelf and assumed it was flour. The father and son ate the breaded and fried fish with a small amount of alcoholic beverage. About 2 h after the meal they both complained of severe abdominal pain, nausea, and vomiting, for which they called for the ambulance. Case 1 (The Father) In the ED, the father was awake (GCS 15) but illappearing with a blood pressure of 135/85 mmHg, pulse 80 bpm, respiratory rate 18 per minute, body temperature 36.9°C, and pulse oximetry 97%. Physical exam findings were otherwise normal. A few minutes after arrival to the ED, the father had tonic – clonic seizures, which were controlled after IV diazepam, given over several minutes (total 15 mg). The patient received 1 mEq/kg sodium bicarbonate to reverse metabolic acidosis. A nasogastric tube was inserted and activated charcoal was administered. After an additional 10 min, tonic – clonic seizures recurred and persisted despite an additional 10 mg of IV diazepam. He was intubated using midazolam, fentanyl, and vecuronium and admitted to the medical ICU for further management. Laboratory results revealed mildly elevated blood glucose, leukocytosis, and metabolic acidosis (pH: 7.035, bicarbonate: 9.2 mEq/l). The activity level of plasma cholinesterase was normal and screening did not identify cannabinoids, amphetamine, cocaine,
Summary of the laboratory data of the father.
Day 0
Day 1
Day 2
Day 6
Day 10
14 0.79
23 1.7
36 1.5
23 1.3
22 0.9
151.8 4.59 40 41 16 48
143 4.7
150 4.6 37 56 13.7 42
145 4.2 132 255
144 4.2 104 33
N value 7 – 21 1 136 – 146 3.5 – 5.5 5 – 34 5 – 40 13.6 38 – 42
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benzodiazepines, or opiates. His EKG rhythm strip was normal. In the ICU, the patient was treated with mechanical ventilation for two days and then placed in the ward. He was weaned at the end of the first day following relief of seizures and acidosis. Metabolic acidosis resolved without further bicarbonate treatment by the second day, and no other biochemical or hematological abnormalities were detected (Table 1). Renal function tests were normalized after the first day. He did not receive any treatment other than diazepam. An EEG was not obtained because of cessation of seizure activity and the patient was not paralyzed. He was discharged without any sequelae after an uneventful 4-day stay in the hospital. Case 2 (The Son) This patient had a major motor tonic – clonic seizure on the way to the hospital. Shortly after receiving diazepam 10 mg IV, his seizures stopped. He was postictal on presentation. On examination, the patient was comatose (GCS = E2, V1, M4) and had a blood pressure of 125/80 mmHg, pulse 92 bpm, respiratory rate 22 per minute, body temperature 37.2°C, and pulse oximetry 100%. Physical exam findings were otherwise normal, with a non-focal neurologic exam and no papilledema. Laboratory results from the son revealed leukocytosis (WBC = 14000/mm3) concurrent with a severe
metabolic acidosis (pH: 6.920, bicarbonate: 8.3 mEq/l). Tests for plasma cholinesterase activity and screening for cannabinoids, amphetamine, cocaine, benzodiazepines, and opiates were normal. The son received 1 mEq/kg sodium bicarbonate to reverse metabolic acidosis. A nasogastric tube was inserted to give activated charcoal. After an additional 10 minutes, tonic – clonic seizures recurred and persisted despite an additional 10 mg of IV diazepam. As a result, he was intubated orotracheally using midazolam, fentanyl, and paralyzed with vecuronium and then was admitted to the medical ICU. Standard ventilation settings for age and weight were administered as no pulmonary complication was encountered. Seizures did not recur after resolution of the metabolic acidosis so an EEG was not obtained. The metabolic acidosis resolved at the end of the first day, but acute oliguric renal failure (ARF) was identified in the second day, with a BUN level of 47 mg/dl and creatinine 6.4 mg/dl (see Table 2). CPK (1020 IU) and myoglobin (426 ng/ml) levels also rose significantly in the second day despite the absence of myoglobinuria. Aggressive fluid treatment was followed by a decrease in BUN (35 mg/dl), creatinine (1.7 mg/dl), CPK (62 IU/l), and myoglobin (44 ng/ml). The ARF, which was thought to result from rhabdomyolysis, resolved. The clinical picture improved by the tenth day. Nearly 2 months later, his serum BUN and creatinine were within normal limits.
Table 2. Laboratory follow-up results of the son. Test
Day 0
Day 1
Day 2
Day 4
Day 6
Day 10
Day 13
Day 25
N value
BUN (mg/dl) Creatinine (mg/dl) Na (mEq/l) K (mEq/l) CPK (IU/l) Myoglobin (ng/ml) AST (U/l) ALT (U/l) Hemoglobin (g/dl) Hematocrit (%) Creatinine (urine) Na (urine) mEq/lt Density (urine) pCO2 (mmHg)* pO2 (mmHg)* pH (blood)
16 0.7 138 3.5
20 1.4 140 4.2
47 6.4 137 3.7 1020 426 171 61 11.6 40
57 8.3 135 3.6 1150 438
66 7.2 137 3.5 847 175 83 59 11.4 33.8
35 1.7 135 5 62 44
21 1 139 4.2 25
13 0.9 138
7 – 21 1 136 – 146 3.5 – 5.5 10 – 200
*Arterial blood gases.
28 19 13.7 42 19.9 69.5 1005 28.6 105 7.08
7.38
7.49
5 – 34 5 – 40 13.6 38 – 42
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DISCUSSION Humans commonly experience sweating, headache, vomiting, and dizziness after ingestion of DDT (3). The agent specifically blocks nerve transmissions of impulses in the brain and inhibit GABA receptors. These effects result in agitation, confusion, and generalized convulsions with abrupt onset. Seizures can be the sole manifestation of toxicity and appears within 1 to 2 h following empty-stomach ingestions. They can be delayed for 5 to 6 h in the case of a full stomach (1,3,5). Hyperthermia can be seen as protracted muscle fasciculations, agitation, and seizure activity. Treatment encompasses measures to alleviate body temperature (e.g., wetting and fanning) (4). Fever is reported to have no correlation with symptom severity (9). Additional findings in severe poisoning include respiratory insufficiency, aspiration pneumonitis, hyperthermia, and metabolic acidosis that may develop in 4 to 8 h (8). In the present report, both cases experienced seizures as generalized convulsions associated with loss of consciousness (i.e., grand mal), nearly 2 h after the ingestion. Seizure activity is one of the manifestations expected in the poisoning (10 –13). Both patients were documented to have severe metabolic acidosis following DDT ingestion. Severe poisoning with these compounds has been associated with metabolic acidosis (8), probably secondary to protracted seizure activity (4). Our 15-year-old patient exhibited transient oliguric ARF a few days after the toxic exposure. There was no evidence of hypotension, hypoxia, or other drug ingestions. Although there was no myoglobinuria in our case, the renal failure could result from myoglobin deposition in the renal tubules, a consequence of rhabdomyolysis. In one study, 26 percent of patients with rhabdomyolysis did not have myoglobinuria (14). Myoglobin is expected to be excreted via urine only when plasma concentration is in excess of 1.5 mg/dl. The absence of myoglobinuria in the patient could be related to the low levels documented. No report of ARF attributed to DDT ingestion was found, but related compounds were involved in two fatal exposures (15,16). Koschier et al. demonstrated that a major metabolite of DDT [bis(p-chlorophenyl) acetic acid] could cause some form of impairment in the nephron function (17). Seizures resulting from DDT toxicity could be the main culprit triggering the metabolic acidosis in the son. Consequent high levels of CPK and myoglobin might
have caused the rhabdomyolysis-related ARF. The absence of ARF in the father may have been due to dose-dependent factors and was understood only later during his admission. Then we were able to obtain a more detailed history and learned that his son had eaten most of the fish. This might explain the nephrotoxicity occurring in the son, but not in the father. In our patients, DDT poisoning was presumed depending on the clinical picture. DDT metabolites were not looked for in body parts and fluids; instead, the laboratory confirmed that the ‘‘dust’’ ingested by the patients was ‘‘pure’’ DDT. Blood levels of DDT have not been available, and they are irrelevant to the clinical course (4). Searching for myriad types of substances in the busy ED environment is not practical. Many diagnostic studies such as adipose tissue biopsy or gas chromatography are time consuming and thus are of no use in the management of patients with acute poisoning (2,4,5). Several reports have mentioned suicidal or accidental poisoning with DDT, mainly in agricultural and underdeveloped regions (4,9,18,19). Our report is unique in describing two patients with severe DDT poisoning due to ‘‘misuse’’ of the agent, which has long been banned in many countries. The patients kept the pesticide among household supplies under illegal circumstances. More importantly, use and distribution of these materials are illegal in the country. The mistake made at this dinner fortunately did not result in any fatalities. Official measures should be strengthened and public awareness enhanced in the developing world regarding use of these insecticides. Obtaining a detailed history is of utmost importance in the management. The patient’s spouse reported that the ingested powder was DDT that she had bought as a pesticide. Since the admission was late for routine laboratory workup, we kept a sample of the substance and sent it for analysis the following day. The laboratory confirmed that the agent was DDT.
CONCLUSION An accurate history and general supportive care are of critical importance in the management of any poisoning. The differential diagnosis of patients presenting with acute seizures should include DDT, particularly in developing countries. Public health and legal measures have reduced the number of unintentional ingestions of DDT but stricter regulation and control of the distribution, labeling, and marketing of such products may be needed.
Toxicity Following Unintentional DDT Ingestion
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