Paraquat Toxicity- update 2

A) MANAGEMENT OF MILD TO MODERATE TOXICITY 

• Following decontamination, supportive care is the mainstay of care. 
• Glucocorticoids (dexamethasone 5 mg IV every 6 hours) with cyclophosphamide (15 mg/kg) in 200 mL of D5NS over 2 hours daily for 2 days) should be administered to a patient at risk of moderate or severe pulmonary toxicity and those with symptoms consistent with moderate to severe toxicity. 

B) MANAGEMENT OF SEVERE TOXICITY 

• Following decontamination, supportive care is the mainstay of care. 
• Aggressive fluid resuscitation should aim to replace fluid losses and maintain renal blood flow in order to augment toxin elimination. 
• Glucocorticoids (dexamethasone 50 mg IV every 6 hours until PaO2 is greater than 80 mmHg then gradual taper) with cyclophosphamide (15 mg/kg in 200 mL of D5NS over 2 hours daily for 2 days) should be administered. 

C) DECONTAMINATION 
PREHOSPITAL: DERMAL EXPOSURE: 

• Remove contaminated clothing and wash thoroughly with soap and water. 

HOSPITAL: DERMAL EXPOSURE: 

• Remove contaminated clothing and wash thoroughly with soap and water. 
• Care should be taken not to abrade the skin because disruption of the stratum corneum may lead to increased toxin absorption. 

INGESTION: 

• Patients with a recent ingestion should receive nasogastric suction with a soft, small gauge tube in order to remove any liquid remaining in the stomach. 
• After gastric decontamination with an NG tube, aggressive antiemetic therapy should be provided to facilitate administration of the adsorbent agent. 
• Patients with an ingestion should be given one of the following: 
• ACTIVATED CHARCOAL: 
• ADULT: 50 to 100 g; CHILD: 1 g/kg)
• BENTONITE CLAY (7% solution): 
• ADULT: 100 to 150 g; CHILD less than 12 years of age: : 2 g/kg; or 
• FULLER'S EARTH (30% solution) 
• ADULT: 100 to 150 g; CHILD less than 12 years of age: 2 g/kg). 
• AVOID: Gastric lavage is NOT recommended because of corrosive injuries imparted by the solution itself may increase the risk of iatrogenic perforation. 
• OCULAR EXPOSURE: Copious irrigation with saline or sterile water and ophthalmology consultation. 

D) AIRWAY MANAGEMENT 

• Airway support should be considered for patients with severe CNS depression or those at risk of aspiration. 

E) ANTIDOTE 

• There is NO antidote available for paraquat toxicity. 

F) HYPOTENSION 

• Treat hypotension with isotonic fluid resuscitation until the patient is felt to be euvolemic, followed by addition of vasopressors in standard doses. 
• Cardiac dysrhythmias should be treated according to typical ACLS protocols. 

G) OXYGEN THERAPY 

• In general, oxygen therapy should be withheld until the PaO2 is below 50 mmHg, because supplemental oxygen may lead to increased production of oxygen free radicals and increased pulmonary toxicity. 
• Lung transplantation may be considered late in the course for patients with severe pulmonary injury and subsequent hypoxia after the serum paraquat concentration is zero. 

H) NAUSEA AND VOMITING

• Treatment is supportive with care to ensure replacement of gastrointestinal fluid losses. Antiemetics should be provided liberally (Ondansetron: Adult: 4 to 8 mg IV; Children: 0.15 mg/kg IV). Stress ulcer prophylaxis should be provided, since patients are likely to have corrosive injury due to the ingestion. 

I) ACUTE TUBULAR NECROSIS 

• Renal injury is due to acute tubular necrosis and is largely reversible. Adequate fluid resuscitation is key to limiting secondary renal injury. 
• Hemodialysis for oliguric renal failure is occasionally necessary as a temporizing measure until renal function improves. 

J) SEIZURES 

• Seizures should be treated with benzodiazepines. 

K) ENHANCED ELIMINATION 

• In general, NO method of enhanced elimination (ie, dialysis, hemofiltration, or hemoperfusion) has been effective at improving survival. 
• However, due to the inherent toxicity of the agent, the rapid progression of renal injury, and the lack of effective interventions, hemoperfusion, hemodialysis or hemofiltration is recommended early in the course of significant ingestions to decrease serum paraquat concentrations. 
• Hemoperfusion, if done during the first 2 hours of exposure, is the preferred method of extracorporeal elimination, if available. 

F) IMMUNOSUPPRESSIVE THERAPY 

• The combination of corticosteroids and cyclophosphamide has been shown in a randomized, controlled study to reduce mortality in severe paraquat poisoning (Lin et al, 2006). 
• The protocol used in one study was as follows (Lin et al, 2006): 
• Gastric lavage followed by administration of 1 gram/kilogram of activated charcoal in 250 milliliters of magnesium citrate in patients presenting within 24 hours of ingestion. 
• Two 8 hours courses of activated charcoal hemoperfusion within 24 hours of paraquat ingestion. 
• After hemoperfusion, administer intravenous cyclophosphamide 15 milligrams/kilogram/day in 200 ml D5NS infused over 2 hours for two consecutive days. Also administer 1 gram methylprednisolone in 200 milliliters D5NS infused over 2 hours daily for 3 consecutive days. 
• After the initial pulse therapy, administer dexamethasone 5 milligrams intravenously every 6 hours until PaO2 is 80 mmHg (11.5 kPa) or greater. 
• If PaO2 < 60 mmHg (8.64 kPa), repeat intravenous methylprednisolone 1 gram in 200 milliliters D5NS infused over 2 hours daily for 3 consecutive days. If WBC > 3000/m(3) and it has been 2 weeks since the initial pulse of cyclophosphamide, repeat intravenous infusion of cyclophosphamide 15 milligrams/kilogram in 200 milliliters D5NS infused over 2 hours as a single dose. 
• Then continue intravenous dexamethasone 5 milligrams every 6 hours until PaO2 is 80 mmHg (kPa 11.5) or greater. Then reduce dexamethasone dose gradually. 

NAC Regimen

• The New Zealand Poison Centre (TOXINZ) on the other hand suggested NAC for the treatment of paraquat poisoning as follows:
• The use of N-acetylcysteine for bipyridylium herbicide poisoning has not been proven effective.
• N-acetylcysteine is recommended following any moderate to severe exposure to bipyridylium herbicides. It is considered unlikely to alter the course of those suffering fulminant poisoning where death occurs within one week from multiple organ failure.
• Dose and Administration
• CHILD
• As yet to be determined, but likely the same as the adult regimen
• ADULT
• Loading dose:
• 150 mg/kg N-acetylcystein in 200 mL 5% dextrose in water infused IV over 15 minutes
• Continued infusion: 300 mg/kg N-acetylcysteine in 1,000 mL 5% dextrose in water infused IV over 24 hours

reference:

1. Pusat Racun Negara
2. Micromedex
3. New Zealand Poison Centre (TOXINZ)