Paraquat intoxication

INTRODUCTION —

Paraquat (1,1-dimethyl-4,4'-bipyridylium chloride) (since 1962)

completely denatured upon contact with the earth

PREPARATIONS —

liquid concentrate (29 percent) dissolved in water (2.5 to 10 percent) aerosol (0.2 percent). 估計的致死劑量（ lethal dose ）：在成人約為 2 到 4

克（＝ 20% 的巴拉刈溶液食入 10 到 20 毫升） 農藥生產商在巴拉刈農藥中添加催吐劑，可引起中毒

者早期的嘔吐，以減少吸收。 台灣常見的產品種類包括： 24﹪ 的速草淨（正豐）、

綜免刈（功力）、全草滅日農、巴拉刈、草蕪松（興農）、克無蹤以及 42﹪ 的巴達刈

TOXICITY AND METABOLISM — herbicidal activity :

by inhibiting the reduction of NADP to NADPH during photosynthesis → superoxide, singlet oxygen, hydroxyl, and peroxide radicals → destroy lipid cell membranes by polymerization of unsaturated lipid compounds → oxidative destruction → recruitment of inflammatory cells → late and irreversible pulmonary fibrosis

In Vivo

pulmonary toxicity : highest oxygen tensions (alveoli) found in the body.

kidney toxicity : acute tubular necrosis (within 24 hours) → enhancing overall toxicity.

口服的巴拉刈僅有 5 到 10% 會經由腸胃道被吸收，其餘部分由糞便排出。

巴拉刈於腸胃道的吸收相當快速，約於 0.5 至2 小時內即達到血中濃度的高峰

林口腎臟科 許翔皓 腎臟 -- 第三個小時即達到頂點 / 最主要的排泄器官。 肺臟，多胺系統（ polyamine system ）主動運輸的方

式累積在肺泡細胞內 : 第五至七個小時之後，肺的巴拉刈濃度會是所有身體的器官中最高的。

腎臟功能正常，百分之八十至九十的巴拉刈都會在 6小時內從尿液中排出，在 24 小時以內則幾乎百分之百都會由腎臟排出。

腎功能不正常，則巴拉刈的排泄會受到很大的影響，組織中（尤其是肺臟）和血液中的巴拉刈濃度將大幅增高，且其濃度將延遲到 15 至 20 小時之後才達到頂點，甚至於存留體內更長的時間。

ameliorate the toxic effects of paraquat: deferoxamine (Complexes with trivalent ions (ferric ions) to form fe

rrioxamine, removed by the kidneys removal of iron) : Lipid peroxidation may be enhanced by iron radicals.

Vitamin E (a potent antioxidant) : only in cultured cells ; no clinical effect

Exogenous glutathione and n-acetylcysteine, a donor of glutathione, may protect against injury.

Sulfite or thiosulfite (redox agents) (reversing oxidized glutathione).

CLINICAL EXPOSURE —

Skin and lungs —infrequently results in systemic toxicity0.4 percent of a topical dose was absorbed from an unoc

cluded site;

1.4 percent was absorbed from an occluded site; and

3.8 percent was absorbed from an occluded and damaged dermal site [13].

thermal-dependent conversion of paraquat to non-toxic bipyridines.

GI tract —cause systemic toxicity + direct injury to the gastrointestinal tract

CLINICAL TOXICITY —

due to absorption via the gastrointestinal tract.

Direct local toxicity Systemic toxicity — results from the oral

ingestion

Direct local toxicity

GI tract — result from the caustic properties of paraquat:1. Within a few minutes to hours → a burning sensation in the buccal cavity. 2. within one to two days → Ulceration of the lips, tongue, and pharynx ("pseudomembrane") → esophageal perforation.

Skin — skin rashes (particularly on scrotal and intergluteal areas), cracked nails, and epistaxis

Lungs —hemoptysis. Eyes — Corneal ulceration and scarring.

Systemic toxicity — results from the oral ingestion Ingestion of moderate amounts — oral inge

stion of amounts of paraquat approximately between 4 to 30 mL/kg of the liquid concentrate:

Ingestion of massive amounts — greater than 30 mL/kg or 50 mL of concentrate.

Ingestion of moderate amounts —

Buccal and/or esophageal ulcerations. Renal failure (within two to six days) - Proxim

al tubule dysfunction. Metabolic acidosis-- myocardial failure (my∵

ocarditis+ epicardial hemorrhage with arrhythmias), adrenal gland insufficiency (due to necrosis), systemic hypotension, severe hypoxemia, and/or renal failure.

Ingestion of moderate amounts —

Pulmonary edema (24 to 48 hours after ingestion) → adult respiratory distress syndrome (first week after ingestion) : diffuse consolidation, pneumomediastinum with or without pneumothorax and subcutaneous emphysema, and cardiomegaly with widened superior mediastinum→ pulmonary fibrosis.

喘的出現時間相對上會較晚，約在中毒後第 3 至 14 天才逐漸出現

Death usually occurs within one to two weeks, but may be observed up to six weeks after ingestion.

LABORATORY DETECTION —

A qualitative urine test for paraquat : concentrations of 1 mg/mL or above (1 ppm)

Gas chromatography and high pressure liquid chromatography : levels of 0.1 to 0.2 mg/dL.

Radioimmunoassay : levels well below 0.1 mg/mL.

Association with prognosis — Fatal outcomes : plasma levels > 0.2 mg/mL

at 24 hours after ingestion / 0.1 mg/mL at 48 hours.

TREATMENT —

Prevention of gastrointestinal absorption —

Removal from blood —ineffective in removing paraquat → maintenance of renal function

Ancillary treatment —

Prevention of gastrointestinal absorption — Gastric lavage : performed cautiously in view of possi

ble ulceration of the pharynx and the esophagusdiatomaceous clays(=bentonite + Fuller's earth 30% suspension)+ magnesium sulfate, to produce a catharsis.bentonite in a 6 to 7.5 percent suspensionsuspensions of activated charcoalthe ion-exchange resin sodium resonium (Kayexalate®)

Total gut lavage polyethylene glycol solutions for bowel irrigation

Removal from blood —maintenance of renal function Extracorporeal removal — (moderate to low dose 4 to 30 mL/kg) : hemoperfusion within 12

hours of poisoning may reduce mortality > hemodialysis. -- up to two to three weeks after an ingestion

charcoal hemoperfusion more rapid reduction in plasma concentrations.

a new zeolite resin tested in vitro shows promise of a high degree of adsorption, although it has not yet been used clinically

血液灌注應儘快於巴拉刈中毒 12 小時內執行，黃金時間為食入 6小時內。必須 24 小時內做血液灌注才有臨床意義，超過 24 小時則因巴拉刈皆已被肺、肌肉等組織所吸收及累積，此時移除血液中少量緩慢釋出的巴拉刈分子效果相當有限。

Ancillary treatment —

Immunosuppression — use of cyclophosphamide combined with corticosteroids:

Nitric oxide (not an established therapy, case report) — addition of nitric oxide (NO 25 ppm) to inspired gases→ transient improvement in arterial oxygenation in a single case report. In this,

Deferoxamine —Complexes with trivalent ions (ferric ions) to form ferrioxamine, which are removed by the kidneys

Pulmonary transplantation —without success

SUMMARY AND RECOMMENDATIONS — ingested greater than 4 mL/kg of paraquat concentrat

e - administration of intestinal decontaminants + daily four to six hour hemoperfusion (or high efficiency hemodialysis) sessions. Daily hemoperfusion or hemodialysis treatment × 2~3 weeks. until paraquat is no longer detectable in blood.

Low-inspired oxygen therapy should be given until it becomes impractical in the face of hypoxemia.

The administration of steroids and cyclophosphamide may be considered.

More unconventional therapy with deferoxamine and nitric oxide inhalation may also prove useful.