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Science Postprint 1(1): e00011. doi:10.14340/spp.2013.12C0006
Science Postprint / www.spp-j.com
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
delayed [1] [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
Clinical Trial
Kouichi Tanabe 1, 2 ,Tomoaki Ikezaki3 ,Atsuko Takano4 ,Takayuki Suzuki4 ,Hidenori Kitazawa3 ,Teiichi Terasaki4 ,Mai Tanaka3 ,Miyako Takeuchi3 ,Kaori
Yamatani3 ,Jun Ohkubo3 ,Aya Handa3 ,Atsumi Nitta2 ,Tatsuhiko Kashii1 ,Nozomu Murakami5
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 nonspecic 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
Abstract
Introduction
A case report of organophosphorus pesticide poisoning resulted in
delayed severe lower intestinal hemorrhage
Author info: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
Recieved: Nov 14 2013 Accepted: Dec 20 2013 Published: Dec 25 2013
Citation: Kouichi 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
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).
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 modications or adaptations are made.
Funding: This case report was not supported by any funds.
Competing interests: No conflict of interest.
Donation message: Your support would be highly appreciated for our further
research.
Ethics statement: This case report was approved by ethical committee of Saiseikai
Takaoka Hospital of Toyama Prefecture. (The approved number is 251202-01.)
Corresponding author: Kouichi Tanabe
Address: Department of Medical Oncology Toyama University Hospital 2630
Sugitani, Toyama-shi, Toyama pref., 930-0194, Japan
E-mail: tanabeko-mi@umin.ac.jp
Case report
Clinical Medicine Emergency and Critical Care
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Science Postprint 1(1): e00011. doi:10.14340/spp.2013.12C0006
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Examination items Laboratory data
AST (GOT) (IU/L) 57
ALT (GPT) (IU/L) 26
LDH (IU/L) 307
ALP (IU/L) 238
γ-GTP (IU/L) 36
CPK (IU/L) 163
Cholinesterase (IU/L) 2
Creatinine (mg/dL) 0.8
Uric acid (mg/dL) 3.6
Urea nitrogen (mg/dL) 25.4
Na (mEq/L) 137
K (mEq/L) 3.7
Cl (mEq/L) 106
GLU (mg/dL) 438
Troponin T(ng/dL) (-)
BNP (human brain natriuretic P) (pg/mL) 13.3
CPR (mg/dL) 0.05
WBC (×104/μL) 20.2
RBC (×106/μL) 5.49
Hb (g/dL) 18.2
Hematocrit (%) 55.9
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
Neutrophils (%) 78.6
Lymphocytes (%) 17.3
Monocytes (%) 2
Eosinophils (%) 1.4
Basophils (%) 0.6
Table 1: Laboratory data on admission
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 conrmed 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
ndings 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.
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 classied 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
Discussion
Course of treatment (Figure 1)
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methanol contained as the solvent [6] and hemorrhagic aspiration
pneumonia caused by other organic solvents has only been
indicated[7]. The main cause of death in organophosphorus
poisoning has been reported to be central respiratory failure [8].
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 inltrative 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 reports[9-11]. Two of these reports described cases of upper
gastrointestinal bleeding and perforation, but did not nd a cause-
effect relationship between the ingestion of organophosphorus
compounds and these symptoms [9] [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
Figure 1 : Clinical course
resulted in severe constipation, leading to rectal ulceration and
bleeding from it [11]. 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 acceleration [12] [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 impairment [14]. A
few cases of pulmonary thromboembolism associated with
organophosphorus poisoning have been reported previously [15].
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,
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Science Postprint 1(1): e00011. doi:10.14340/spp.2013.12C0006
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Figure 3 : Imaging studies
A pipe-like segmental narrowing of the sigmoid colon with mural
sclerosis was noted.
Figure 2 : Imaging studies
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.
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 difcult.
Barium enema examination (59th hospital day): A 10-cm, apple-core stricture was observed in the sigmoid colon.
a.
b.
c.
Figure 4 : Microscopic image of the narrowed sigmoid colon segment
Chronic full-thickness ulcer (ul-IV). Regeneration of the mucosal surface with associated hemorrhage was
incomplete in some areas (HE, ×20).
Subserosal brosis was marked, and thrombotic occlusion of middle- and small-sized arteries was observed (HE,
×40).
Mucosal epithelium had regenerated, but incompletely in the glandular body (HE, ×100).
a.
b.
c.
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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 subcutaneously [16].
Although the pharmacokinetic disposition of NPE is unclear,
it has been reported that nonyphenol (NP) is produced
through microbial degradation [17]. 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 chronicity [18]. 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 gures.
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.
Acknowledgement
Author contributions
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