Paresthesias Is this Diabetes?
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Your next patient…
A 58 year old male, with a history of well-controlled type
II Diabetes, presents to his PCP with numbness
and tingling of his hands. He has had 3
episodes, with the paresthesias in different areas of
his hands; the first episode was a few months ago.
Each episode lasts approximately 12-24 hours. The
symptoms worsen when he washes his hands.
Nothing makes it better.
(Source: Case from Sudakin, 2004)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Thoughts?
At this point, what is
your differential?
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Differential for paresthesias
A few causes…
• Alcoholism
• Diabetes Mellitus
• Entrapment neuropathy (eg Carpal Tunnel)
• Nerve Root compression
• Hypocalcemia
• Vitamin B12 deficiency
• Toxins: metals, pesticides, industrial agents
• Etc, etc…
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Case – Objective Data
Mild decrease in sensation to light touch of the
right index finger, and the dorsum of the left
index finger and thumb.
Paresthesias are exacerbated by warm
temperature stimulus.
No other abnormal findings.
6 months ago his A1C was 6.0
Urine dip today has trace protein.
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Some providers might…
Plan: Assuming diabetes at this point:
• Schedule a nerve conduction study,
• A1C today,
• Follow-up in one week.
Result:
His symptoms went away the next day. And so, he
did not go to the nerve conduction study and
cancelled the follow-up appt with his PCP.
WHAT WOULD YOU DO DIFFERENTLY?
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pesticides - Epidemiology
• 97, 677 human exposures reported to the
Toxic Exposure Surveillance System involved
pesticides in 2003.
• 41 of these resulted in death, 3 involved
pyrethroids
• 50, 938 were in children less than 6 years old
• 36,964 were in adults over 19 years old
(Source: Watson et al., 2004)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Epidemiology
• Of the pesticide exposures, 21,135 involved
Pyrethroids or Pyrethrins in 2003
– 32% were in children < 6 years old
– 2% were intentional
• Outcomes were reported in half of these
– 16% had no adverse health outcomes
– 5% had moderate to severe outcomes or death
THESE ARE JUST REPORTED EXPOSURES
(Source: Watson et al., 2004)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - History
• Pyrethrum is derived from the chrysanthemum
• Pyrethrum is made up of six chemicals with
insecticidal properties, called pyrethrins
• Pyrethroids are synthetic analogs of pyrethrins,
made to last longer and be more toxic to insects.
– Type I – shorter duration of effects
– Type II – longer acting, enhanced by addition of cyano
group
(Source: ATSDR, 2003; Bradberry et al., 2005; Proudfoot, 2005)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Least to most Toxic
Toxicity in General
•
•
•
•
Pyrethrins
Pyrethroids - Type I
Pyrethroids - Type II
Pyrethroids + synergist or other
pesticide
(a synergist increases toxicity by slowing metabolism)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Type I - pesticides
Type II (cyano) - pesticides
•
•
•
•
•
•
•
•
permethrin
pyrethrins
bioallethrin
cismethrin
fenvalerate
cyhalothrin
deltamethrin
cypermethrin
Type I - poisonings
Type II - poisonings
•
Severe fine tremor
•
Profuse watery salivation
•
Marked reflex hyperexcitability
•
Coarse tremor
•
Sympathetic activation
•
Increased extensor tone
•
Paresthesia (dermal exposure)
•
Sympathetic activation
•
Choreoathetosis
•
Seizures (dermal exposure)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Current Uses
• Domestic – e.g. bug bombs, mosquito nets,
insect sprays
• Medical - e.g. treatment of scabies and lice
• Commercial – e.g. insecticide for agriculture
• Veterinary – e.g. pet shampoos, fleas
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Some Pyrethroid/thrin Products
• Nix – Lice treatment
• Elimite – Scabies treatment
• Drione – home pesticide dust: ants,
cockroaches,etc
• Raid! – for many household pests
• Rid – Lice treatment
• Hartz - dog pest control drops
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Mechanism of Action
• Acts primarily on voltage dependent sodium
channels – leading to hyperexcitable state, also
affects chloride channels to increase excitability
• Increases adrenal activation – increasing
adrenaline
• Duration of effect is determined by the structure
of the offending pyrethroid
(Source: ATSDR, 2003; Bradberry et al., 2005; Proudfoot, 2005)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Toxicokinetics/dynamics
• Absorption:
– GI: moderate
– Respiratory Tract: moderate
– Dermal: poor
• Usually metabolized quickly by the liver
• Excreted primarily in urine, less in feces
• Half life – usually 5-20 hours, can be days (Brad, Ray,
Perry)
• Often combined with synergist (e.g. piperonyl) to
enhance killing power & slow degradation
• Lipophilic, may concentrate in fat tissues (ATSDR, 2003;
Ray, 2000)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Exposures
• Diagnosis from symptoms alone can be difficultEnvironmental and Occupational Health History is
essential!
• Do not confuse with other pesticides e.g.
organophosphates, treatment is different!
• Find out exactly what the product was, “inert” or
“inactive” ingredients are important too!
• Ask for the label, or MSDS when possible
• Call a poison control center for assistance.
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Dermal
• Signs/Symptoms
– Paresthesia (from activity on peripheral nerve fibers
delayed closing of sodium channels) stinging, itching,
burning, tingling
•
•
•
•
Most commonly the face is involved
Exacerbated by sunlight, water, scratching, and sweating
Onset: 0.5- 2 hours
Recovery within 30 hours
– Erythema and blisters are rare
– Allergic reactions rare
(Source: Bradberry et al., 2005; Proudfoot, 2005; Reigart & Roberts, 1999)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Dermal
• Management
– Decontamination
• Wash promptly with soap and plenty of water
• Avoid vapor contact with face and eyes, using Protective
Equipment as necessary.
– Vitamin E Oils can be effective in easing
paresthesias (dL-alpha tocopheryl acetate)
– Patient Education to prevent future exposures
• Use of proper Protective Equipment, following pesticide
label instructions
(Source: Bradberry et al., 2005; Proudfoot, 2005; Reigart & Roberts, 1999)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Ocular
• Signs/Symptoms
– Mild eye irritation
– Rarely Miosis
– Can be corrosive!
• Management
–
–
–
–
Prolonged flushing
Flourescein exam for possible corneal injury
Refer to ophthalmology as needed and if irritation persists
Patient Education! Take all precautions to avoid ocular
exposures!
(Source: Bradberry et al., 2005; Proudfoot, 2005; Reigart & Roberts, 1999)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Inhalational
Aerosolized droplets or dust are inhaled
• Signs/Symptoms
– Nasal and respiratory irritation
• Wheezing, chest tightness, SOB, cough, sneezing,
rhinorrhea, lacrimation
• More pronounced in asthmatics and smokers
– May be followed by systemic effects
(Source: Bradberry et al., 2005; Proudfoot, 2005; Reigart & Roberts, 1999)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Inhalational
• Management
– Symptomatic treatment
– Monitor for systemic toxicity
– Patient Education!
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Ingestion
• In the U.S. we regularly ingest tiny amounts when eating
fruits and vegetables sprayed with pyrethroids.
• Pyrethrin, the most commonly used pyrethroid, has an
average daily intake in the U.S. about 1,000 times less
than the acceptable daily intake.
• Little is known about the effects of chronic exposure.
(ATSDR, 2003)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Ingestion
• Signs/Symptoms
– Sore throat
– ~50% have Nausea/vomiting
– Abdominal pain
– +/- GI mucosa ulceration
– +/- increased secretions
– +/- dysphagia
(Source: Bradberry et al., 2005; Proudfoot, 2005; Reigart & Roberts, 1999)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pyrethroids/thrins - Ingestion
• Management
– Potentially toxic dose = 100-1000mg/kg (Lamb, 2007)
– Monitor for systemic toxicity in large doses
– Consider GI decontamination if the patient is seen soon
after exposure, and a possibly toxic amount was ingested
• Consider lavage only if < 1 hour since ingestion
– Not proven benefits over risks!
– Only recommended with deadly amounts ingested
– Contraindicated with hydrocarbon ingestion (a common
ingredient in many pesticide products)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Gastric Lavage
• Not generally recommended as common components of
these product increase aspiration risk
(Bradberry, 2005)
• Consider cuffed endotracheal tube before lavage if the
patient is neurologically impaired
• First control seizures as needed with IV diazepam
• Insert orogastric tube
• Usually normal saline is used, then aspirate back to attempt
removal of poison
• Lavage performed >60 minutes after ingestion increases
risk of perforation, bleeding, and scarring = NOT
RECOMMENDED
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Catharsis
• Increases gut motility to hasten excretion of
poison
• Not to be the only management method
• Contraindications: abdominal trauma,
perforation, obstruction, no bowel sounds,
volume depletion, hypotension, imbalanced
electrolytes
• Sorbitol – one-time dose only
– Adults : 70% sorbitol, 1-2 mL/kg
– Children: 35% sorbitol, 1.5-2.3 mL/kg (max 50g)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Activated Charcoal
• The goal is to have the charcoal absorb the poison,
and the patient does not.
• Limited evidence with pyrethroids (Bradberry, 2005)
• Unknown if it is helpful if > 60 minutes from ingestion
• Some mixtures contain sorbitol!
• May use even if currently vomiting
• Contraindications: unprotected airway, GI trauma
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Syrup of Ipecac
• RARELY recommended
unless poison control suggests otherwise
• Not routinely used for poisonings
• If used, use < 60 min after ingestion
• Use only if patient is alert, airway protected
(reflexes intact)
• Contraindicated: If life support is likely to be
needed in < 60 min
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Systemic Toxicity
• Often complicated by toxicity of other ingredients in the
product
• Signs/Symptoms: sympathetic activation
– Type I Pyrethroids
• Reflex hyperexcitability
• Fine tremor
– Type II Pyrethroids (+cyano group)
•
•
•
•
Salivation
Hyperexcitability
Choreoatheosis
Seizures
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Systemic Toxicity
Management
• Difficult to control with anti-convulsants
• Pentobarbitone for Type II may be helpful (helps rats)
• Physiologic – Detoxification is by ester hydrolysis in
blood and liver
(Source: Bradberry et al., 2005; Proudfoot, 2005; Reigart & Roberts, 1999)
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Back to the Case – Paresthesias?
Your differential now includes pesticide exposures.
Environmental and Occupational Health History
Ask the patient:
– Past and present: occupation, involvement of
hazardous materials, use of protective equipment
– Home location - near farms, industries, etc.
– Recreational activities/hobbies
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Back to the Case – Paresthesias?
He is a cabbage farmer, and uses lamda-cyhalothrin with
no protective equipment. His symptoms start after
working with this pyrethroid! You use one of your
resources and find this pyrethroid is the likely cause of
his paresthesias, and educate him to follow safety
guidelines on the pesticide label…
AND HE AVOIDS THIS PROBLEM IN THE FUTURE!
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Pesticide Related Illness may be a
Reportable Condition in these states:
Alaska
Arizona
Arkansas
California
Florida
Hawaii
Iowa
Louisiana
Maine
Maryland
Massachusetts
Michigan
Mississippi
Missouri
Nebraska
New Jersey
New Mexico
New York
North Carolina
Oregon
South Carolina
South Dakota
Texas
Utah
Virginia
Washington
Wisconsin
Wyoming
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Resources & References
• NPIC – National Pesticide Information Center
http://npic.orst.edu/
• Reigart, J.R. & Roberts, J.R. (1999). Recognition and
Management of Pesticide Poisonings. Available in
English and Spanish:
http://www.epa.gov/oppfead1/safety/healthcare/handbook/
handbook.htm
• Poison control center information at:
http://ace.orst.edu/info/nptn
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Resources & References
• Agency for Toxic Substances and Disease Registry. (2003). Public
health statement: Pyrethrins and pyrethroids. Retrieved May 11,
2009, from: http://www.atsdr.cdc.gov
• Bradberry, S. M., Cage, S. A., Proudfoot, A. T., & Vale, J. A. (2005).
Poisoning due to pyrethroids. Toxicological Reviews, 24(2): 93106.
• Lamb, J. P. (2007). Pyrethrins and pyrethroids. In K. R. Olson
(Ed.), Poisoning and drug overdose (5th ed.). Retrieved May 14, 2009,
from: http://www.accessmedicine.com. offcampus.lib.washington.edu/
content.aspx?aID= 2678811
• Proudfoot, A. T. (2005). Poisoning due to pyrethrins.
Toxicological Reviews 24 (2):107-113.
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010
Resources & References
• Ray, D. E. & Forshaw, P. J. (2000). Pyrethroid insecticides:
Poisoning syndromes, synergies, and therapy. Clinical Toxicology,
38(2), 95-101.
• Sudakin, D. L. (2004). Pesticide poisoning from synthetic
pyrethroids. CD Summary, 53, 6. Retrieved April 7, 2009 from:
http://www.oregon.gov/ DHS/ph/cdsummary/2004/ ohd5306.pdf
• Watson, W. A., Litovitz, T. L., Klein-Schwartz, W., Rodgers, G. C.,
Youniss, J., Reid, N. et al. (2004). 2003 Annual Report of the
American Association of Poison Control Centers Toxic Exposure
Surveillance System.
Retrieved May 21, 2009, from:
http://www.aapcc.org/archive/Annual%20Reports/03report/Annual%20Repor
t%202003.pdf
Pesticide Health Effects Medical Education Database (PHEMED)
Murphy 2010