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Paresthesias - Is this Diabetes ?

Paresthesias - Is this Diabetes ?. 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

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Paresthesias - Is this Diabetes ?

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  1. Paresthesias -Is this Diabetes?

  2. Your next patient… A 58 year oldmale, 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)

  3. Thoughts? At this point, what is your differential?

  4. 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…

  5. 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.

  6. 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?

  7. 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)

  8. 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)

  9. 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)

  10. Toxicity in General • Pyrethrins • Pyrethroids - Type I • Pyrethroids - Type II • Pyrethroids + synergist or other pesticide Least to most Toxic (a synergist increases toxicity by slowing metabolism)

  11. permethrin pyrethrins bioallethrin cismethrin fenvalerate cyhalothrin deltamethrin cypermethrin Type I - pesticides Type II (cyano) - pesticides Type II - poisonings Type I - poisonings • Profuse watery salivation • Coarse tremor • Increased extensor tone • Sympathetic activation • Choreoathetosis • Seizures (dermal exposure) • Severe fine tremor • Marked reflex hyperexcitability • Sympathetic activation • Paresthesia (dermal exposure)

  12. 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

  13. 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

  14. 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)

  15. 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)

  16. Pyrethroids/thrins - Exposures • Diagnosis from symptoms alone can be difficult- Environmental 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.

  17. 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)

  18. 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)

  19. 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)

  20. 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)

  21. Pyrethroids/thrins - Inhalational • Management • Symptomatic treatment • Monitor for systemic toxicity • Patient Education!

  22. 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)

  23. 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)

  24. 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)

  25. 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

  26. 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)

  27. 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

  28. 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

  29. 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

  30. 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)

  31. 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

  32. 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!

  33. 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

  34. 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

  35. 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): 93-106. • 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.

  36. 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%20Report%202003.pdf

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