A man in his 50’s attempted suicide by ingesting a pesticide, and was emergently admitted to our hospital. On arrival, his consciousness level was GCS 3 (E1VTM1), blood pressure 136/86 mmHg, and pulse rate 57/min. His pupils were miotic (1 mm), and his serum cholinesterase level was 2 IU/L. Since an empty bottle found near his body raised the suspicion of organophosphorus pesticide poisoning, he underwent gastric lavage and gastrointestinal decontamination therapy with activated charcoal, and was administered PAM under mechanical ventilation. Six hours after the ingestion of the organophosphorus pesticide, he responded when his name was called. He was extubated after the return of spontaneous respiration. However, he developed massive melena 2 weeks after the ingestion of the organophosphorus pesticide, and received a total of 30 units of blood. Although melena subsided 2 months after admission, colonoscopy revealed severe stenosis and passage disturbance in the colon, for which he underwent partial colectomy, and was ultimately discharged. The clinical presentation of organophosphorus pesticide poisoning was nonspecific in this patient, and included chemical gastroenteritis and hemorrhagic ulcers. The organophosphorus pesticide ingested by the patient was a 50% emulsion of Dipterex containing approximately 30% methanol as a solubilizer and 5-10% polyoxyethylene nonylphenyl ether (NPE) as a spreading agent. Due to the possibility of NPE adhering to the gastrointestinal tract and causing mucosal injury in this patient, it is necessary to identify the drug composition and ingredients of the pesticide as soon as possible when managing organophosphorus poisoning.
Key words Organophosphorus pesticide poisoning, Gastrointestinal bleeding, Spreading agent
1. Department of Medical Oncology, Toyama University Hospital
2. Department of Pharmaceutical Therapy & Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
3. Department of Pharmacy, Saiseikai Takaoka Hospital of Toyama Prefecture
4. Department of Internal Medicine, Saiseikai Takaoka Hospital of Toyama Prefecture
5. Department of Surgery, Saiseikai Takaoka Hospital of Toyama Prefecture
RecievedNov 14 2013 AcceptedDec 20 2013 PublishedDec 25 2013
CitationKouichi Tanabe, Tomoaki Ikezaki, Atsuko Takano, Takayuki Suzuki, Hidenori Kitazawa, Teiichi Terasaki, Mai Tanaka, Miyako Takeuchi, Kaori Yamatani , Jun Ohkubo, Aya Handa, Atsumi Nitta, Tatsuhiko Kashii, Nozomu Murakami (2013) A case report of organophosphorus pesticide poisoning resulted in delayed severe lower intestinal hemorrhage. Science Postprint 1(1): e00011. doi:10.14340/spp.2013.12C0006
Copyright©2013 The Authors. Science Postprint published by General Healthcare Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 2.1 Japan (CC BY-NC-ND 2.1 JP) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
FundingThis case report was not supported by any funds.
Competing interestsNo conflict of interest.
Donation messageYour support would be highly appreciated for our further research.
Ethics statementThis case report was approved by ethical committee of Saiseikai Takaoka Hospital of Toyama Prefecture. (The approved number is 251202-01.)
Corresponding authorKouichi Tanabe
AddressDepartment of Medical Oncology Toyama University Hospital 2630 Sugitani, Toyama-shi, Toyama pref., 930-0194, Japan
E-mailIf you want to contact author,Please register as a member.
Organophosphorus pesticide poisoning is known to present with a complex of symptoms caused by additives (such as organic solvents, emulsifiers, and spreading agents), as well as neurological symptoms due to the effects of the main ingredient (organophosphate)1. The symptoms of organophosphorus pesticide poisoning have been classified into three categories according to the timing of their appearance: acute, subacute, and delayed1, 2. There have been few reported cases of acute, subacute, or delayed significant lower gastrointestinal bleeding following organophosphorus pesticide poisoning. Recently, we encountered a patient who developed delayed severe gastrointestinal bleeding after ingesting an organophosphorus pesticide, and was treated by blood transfusion and surgical resection for cicatricial sigmoid colon stenosis. We report this patient with a review of the literature because a spreading agent as an additive may have caused delayed gastrointestinal damage.
The patient was a man in his 50’s who had attempted suicide by ingesting a pesticide. He had hypercholesterolemia, for which he received outpatient treatment at a local hospital. He had no remarkable family history. He had a history of discectomy for a lumbar herniated disc at 17 years of age and appendectomy at 28 years of age. He went out of his home, leaving a message saying, "I will have to leave the rest to you." His family members made a frantic search for him, and found him lying in a nearby bush. He was emergently admitted to our hospital.
On admission, his consciousness level was GCS 3 (E1VTM1), blood pressure 136/86 mmHg, and pulse rate 57/min (Table 1). His pupils were miotic (1 mm), and his serum cholinesterase level was 2 IU/L. He had miosis, and bradycardia. He was intubated immediately after admission because he had unstable spontaneous respiration and we needed to prevent him from chemical pneumonia caused by organic solvent contained in pesticide when performing his gastric lavage. The police reported that he may have ingested an organophosphorus pesticide according to the information on the empty bottle found nearby the patient. Because we could not confirm the amount that remained in the bottle before the patient ingested its contents, the amount he ingested remains unknown. (no information was provided regarding the trade name or ingredients of the pesticide product ingested).
|Examination items||Laboratory data|
|AST (GOT) (IU/L)||57|
|ALT (GPT) (IU/L)||26|
|Uric acid (mg/dL)||3.6|
|Urea nitrogen (mg/dL)||25.4|
|BNP (human brain natriuretic P) (pg/mL)||13.3|
|Mean corpuscular volume (MCV, fL)||102|
|Mean corpuscular hemoglobin (MCH, pg)||33.1|
|Mean corpuscular hemoglobin concentration (MCHC, %)||32.5|
|Platelet count (×103/μL)||219|
Gastric lavage was started with 12 L of saline immediately after his admission, and he was administered activated charcoal (50g via nasogastric tube), sodium picosulfate hydrate (0.75%, 10mL via nasogastric tube), pralidoxime iodide (PAM, i.v. at 500 mg/hr until the 2nd hospital day), and an injection of omeprazole (20 mg × 2/day until the 30th hospital day). Thirty minutes after being admitted, he was able to nod when spoken to, and was able to answer questions by shaking his head after 2.5 hours. He was subsequently placed on a respirator, and managed in the ICU. He was extubated approximately 6 hours after admission because his conscious level improved and respiratory condition stabilized, although miosis persisted. However, he displayed marked perspiration and his respiratory condition deteriorated again 25 hours after admission; therefore, he was re-intubated and sedated under mechanical ventilation. His liver function, which had initially deteriorated, normalized, and his ChE levels were slightly higher from the 5th hospital day. He exhibited abnormal behaviors, such as nodding with his eyes open. He was extubated on the 6th hospital day when his respiratory condition stabilized on the 6th hospital day. On the 7th hospital day, his consciousness level improved to GCS 15 (E4V5M6). Atropine sulfate was not administered because he appeared to recover uneventfully after the administration of PAM until the 2nd hospital day.
However, he exhibited strong pharyngeal pain when drinking water, and an upper gastrointestinal endoscopy on the 14th hospital day revealed an acute gastric mucosal lesion (Figure 2 a). On the 15th hospital day, his consciousness level worsened again, and he was placed on mechanical ventilation. We started administration of vancomycin (0.5g × 2 times/day, until the 35th hospital day) because a combination of MRSA pneumonia was suspected from the MRSA detected in his sputum. He developed melena, a nonspecific sign of organophosphorus pesticide poisoning, on the 17th hospital day and we searched for its cause while treating it. When we once again requested the police to provide detailed information on the pesticide ingested, we were informed that its trade name was 50% Dipterex emulsion (Sankei Chemical Co. Ltd.). It contains 50% organophosphate dimethyl-2,2,2-trichloro-1-hydroxyethyl phosphonate (DEP) as the main ingredient, an emulsifier, and an organic solvent (no specific information on the ingredients other than DEP was available). Since DEP alone was unlikely to be the cause of melena, we considered the other ingredients to be the cause. A further search of relevant literature revealed that the organophosphorus pesticide in question contains approximately 30% methanol and 5-10% polyoxyethylene nonylphenyl ether (NPE)3. Since methanol was an unlikely primary cause of melena, NPE was suspected. However, a considerable amount of time had passed since the ingestion of the pesticide; therefore, we decided to administer symptomatic treatment only and perform a follow-up observation.
Since his blood Hb level was slightly reduced, the patient received intermittent blood transfusions on an almost daily basis until the 27th hospital day. Colonoscopy on the 30th hospital day revealed an approximately 20 cm-long, circumferential ulcer in the distal sigmoid colon with easily bleeding mucosa, but confirmed that the bleeding had almost stopped (Figure 2 b). Thereafter, his consciousness level improved, and his respiratory condition gradually stabilized; therefore, he was extubated on the 55th hospital day. The administration of famotidine powder 20 mg in 2 divided doses was continued after he started to intake meals. However, since he exhibited lower abdominal pain, colonoscopy and a barium enema examination were performed on the 56th through 59th hospital days (Figure 2 c), which revealed a narrowing of the sigmoid colon. Therefore, a left colectomy was performed on the 72nd hospital day (the histopathological findings of the resected specimen are shown in Figure 3, Figure 4 a-c). Ultimately, bilateral peroneal paralysis, which appears to be a sequela to organophosphate-induced neuropathy, remained; however, he was discharged on the 122nd hospital day after rehabilitation.
a. Upper gastrointestinal endoscopy (14th hospital day): A deep, undermined ulcer was found in the gastric cardia, and a hypertrophic mucosal fold extending from the proximal side was interrupted at the ulcer margin.
b. Lower gastrointestinal endoscopy (30th hospital day): A circumferential erosion was present in the sigmoid colon, the proximal part of which was severely stenosed, making colonoscope insertion difficult.
c. Barium enema examination (59th hospital day): A 10-cm, apple-core stricture was observed in the sigmoid colon.
A pipe-like segmental narrowing of the sigmoid colon with mural sclerosis was noted.
a. Chronic full-thickness ulcer (ul-IV). Regeneration of the mucosal surface with associated hemorrhage was incomplete in some areas (HE, ×20).
b. Subserosal fibrosis was marked, and thrombotic occlusion of middle- and small-sized arteries was observed (HE, ×40).
c. Mucosal epithelium had regenerated, but incompletely in the glandular body (HE, ×100).
To the best of our knowledge, this is the first report of organophosphate poisoning causing delayed, life-threatening lower gastrointestinal bleeding. It is important to study the causes of bleeding in the present case.
The symptoms of organophosphorus poisoning, mainly including neurological symptoms, have been classified into three categories according to the timing of their appearance: acute symptoms (muscarinic, nicotinic, and central nervous symptoms)4, 5,), subacute symptoms (intermediate syndrome due to the inhibition of neurotoxic esterase and fatty acid amide hydrolase)5, and delayed symptoms (delayed neurotoxicity due to the inhibition of neurotoxic esterase, such as lower extremity motor paralysis and nervous erethism)1, 2, 5. Organophosphorus poisoning is also known to present with a complex of symptoms caused by additives (such as organic solvents, emulsifiers, and spreading agents)1. Specifically, the risk of poisoning by methanol contained as the solvent6 and hemorrhagic aspiration pneumonia caused by other organic solvents has only been indicated7. The main cause of death in organophosphorus poisoning has been reported to be central respiratory failure8. In this study, spontaneous respiration level became low 25 hours after ingestion. This indicated the possibility of intermediate syndrome because we observed marked perspiration and did not observe any infiltrative shadows on a chest X-ray. Furthermore, we observed an aggravation of state of consciousness again on the 15th hospital day, which indicated the cause by gastrointestinal bleeding appeared immediately after the day, anemia, and MRSA pneumonia.
Gastrointestinal bleeding has been described in the following three reports9, 10, 11. Two of these reports described cases of upper gastrointestinal bleeding and perforation, but did not find a cause-effect relationship between the ingestion of organophosphorus compounds and these symptoms9, 10. The remaining report noted that hardened lumps of activated charcoal had been excreted as feces several days before the gastrointestinal bleeding, and concluded that repeated activated charcoal administration resulted in severe constipation, leading to rectal ulceration and bleeding from it11. The basic principles of treating acute poisoning are: digestive tract decontamination, detoxification and antagonist administration, respiratory and circulatory management, metabolic pathway alteration, distribution change, and excretion acceleration12, 13. Based on these principles, we performed gastric lavage on this patient, and administered an antagonist, activated charcoal, and a cathartic. However, despite the absence of constipation and excretion of hardened lumps of activated charcoal, delayed-onset significant lower gastrointestinal bleeding occurred. Organophosphorus poisoning is known to cause vascular endothelial dysfunction, thereby facilitating thrombosis with blood flow impairment14. A few cases of pulmonary thromboembolism associated with organophosphorus poisoning have been reported previously15.
On the other hand, spreading agents contain ingredients that have a protein-denaturing action and cause bleeding on contact with the mucosa. Spreading agents are added to enhance the adhesiveness of pesticides to plants and pests, prolong the duration of action, and improve the insecticidal effect. Of these, NPE contained in the Dipterex Emulsion used by the present patient is a non-ionic surfactant belonging to polyoxyethylene alkylphenyl ethers (AE). Such spreading agents include NPE and polyoxyethylene octylphenyl ether (OPE). All of them have a protein-denaturing action, and have been designated as harmful under the Pollutant Release and Transfer Register (PRTR) Law. In particular, NPE has a potent spermicidal action, and was previously used as the main ingredient of vaginal contraceptive films; however, despite its low dosage, its mucosa-irritating effects posed problems, resulting in it being removed from the market. NPE has also been shown to cause subcutaneous bleeding when administered subcutaneously16.
Although the pharmacokinetic disposition of NPE is unclear, it has been reported that nonyphenol (NP) is produced through microbial degradation17. Previous studies have indicated the possibility that, because the orally administered organophosphorus pesticide becomes pultaceous on the gastrointestinal wall and dissolves gradually, it causes the late development of symptoms and their chronicity18. In this study, the sigmoid-descending colon junction (SDJ) was the region with the most serious stenosis and bleeding. We conjecture that the patient acquired more severe toxicity because he lay supine on the bed for a long time; therefore, gravity and the morphological formation of the colon allowed organophosphorus pesticide to accumulate in the SDJ.
Thus, the possibility that the organophosphorus pesticide caused lower gastrointestinal bleeding in this patient could not be excluded, and its spreading agent was suspected of having aggravated the symptoms. It is necessary to identify the drug composition and ingredients of the pesticide as soon as possible to design and implement the best treatment plan.
In conclusion, delayed-onset lower gastrointestinal bleeding was suspected, and could not be excluded of having been caused by the ingested organophosphorus pesticide and spreading agent as an additive; therefore, when managing organophosphorus poisoning, attention should also be focused on the presence or absence of spreading agents such as NPE, and identifying the ingredients of the pesticide as soon as possible.
We thank Dr. Kazuhiro Matsui of the Department of Pathology at Saiseikai Takaoka Hospital for providing the resected colon specimen.
Tanabe K: Wrote the article and designed the discussion.
Ikezaki T: Wrote the course of treatment and designed figures.
Terasaki T: Performed gastrointestinal endoscopy and colonoscopy on the patient, and edited the article.
Takano A and Suzuki T: Treated the patient, and edited the article.
Kitazawa H: Edited and approved the article.
Tanaka M, Takeuchi M, Yamatani K, Ohkubo J, Handa A and Nitta A: Edited the article and contributed to the quality of the discussion.
Kashii T: Approved the quality of the study, and coordination of the teamwork.
Murakami N: Performed left colectomy on the patient, and edited the article.