Transcript ParaquatIntoxication.ppt

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
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).
ferrioxamine, removed by the kidneys
CLINICAL EXPOSURE —
 Skin and lungs —infrequently results in systemic
toxicity
0.4 percent of a topical dose was absorbed from an
unoccluded 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
ingestion 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) -
Proximal tubule dysfunction.
 Metabolic acidosis-- ∵myocardial failure
(myocarditis+ 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
possible ulceration of the pharynx and the esophagus
diatomaceous clays(=bentonite + Fuller's earth 30%
suspension)+ magnesium sulfate, to produce a
catharsis.
bentonite in a 6 to 7.5 percent suspension
suspensions of activated charcoal
the 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
concentrate 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.