Insecticides, Herbicides, Rodenticides

Chapter 182

Feb. 23, 2006

Poisonings

• 2001 – 90,000 pesticide exposures reported

• Of these, 46, 929 were children under the age of 6

• There were 17 deaths

Types of Exposure

• Three kinds…– Intentional– Accidental– Occupational

– Multiple formulations of the different compounds – always consult Poison Control

Insecticides

• Toxic to nervous system– Four kinds

• Organophosphates• Carbamates• Organochlorines• Pyrethrins

Organophosphates

• Diazinon, Malathion, Orthene, Parathion and chlorpyrifos have been used as chemical warfare agents since WWII

• Sarin, another compound used in the Tokyo subway in 1995

Organophosphates

• Poisoning usually results in accidental exposure in the home, industrial accidents, agricultural sprayings, and in transport of these chemicals

• But also involved in intentional poisonings in homicides

Organophosphates

• If patient presents with poisoning, clinician should ask about first-aid, prehospital interventions, decontamination, product name, manufacturer, product concentration and formulation, circumstances of exposure, amount , onset of symptoms and patient age and medical history

Pathophysiology

• Inhibits the enzyme cholinesterase in the nervous system leading to an accumulation of the neurotransmitter acetylcholine in the CNS, the autonomic nervous system and at neuromuscular junctions.

Pathophysiology

• This accumulation results in overstimulation of the receptors

• The initial overstimulation is followed by paralysis of cholinergic synaptic transmission in the CNS and autonomic ganglia

• A cholinergic crisis results

Aging

• Aging describes the permanent irreversible binding of the compound to the cholinesterase

• Once aging occurs the enzymatic activity is permanently destroyed

• Can take weeks to synthesize new enzyme

Clinical Features

• CNS symptoms of cholinergic excess include anxiety, restlessness, emotional lability, tremor, HA, dizziness, confusion, delirium, hallucinations and seizures

Mnemonic Heaven

• S – Salivation• L – Lacrimation• U – Urination• D – Defecation• G – GI Pain• E - Emesis

• D – Defecation• U – Urination• M – Muscle wkness• B – BBB (Killer B’s)• E – Emesis• L – Lacrimation• S - Salivation

Nicotinic Receptors

• Overstimulation results in pallor, mydriasis, tachycardia, HTN, muscle cramps and fasiculations, and then weakness and paralysis

Special Considerations

• Children are at a greater risk of toxicity due to their size and lower baseline levels of cholinesterase activity

Diagnosis

• Suspicion based on history

• Presence of a suggestive toxidrome

• Laboratory assays

• Testing for specific compounds

Diagnosis

• Diagnosis can be difficult due to a constellation of clinical findings

• Misdiagnoses such as flu or viral syndrome have occurred

Diagnosis

• Noting a hydrocarbon or garlic odor may help

• An initial test dose of atropine that does not result in expected improvement may help in making the diagnosis

Diagnosis

• Unless 2-Pam (pralidoxime) is given before aging occurs, plasma cholinesterase takes up to 4-6 weeks and RBC acetylcholinesterase as long as 90-120 days to return to baseline

Routine Labs

• Routine labs are non-diagnostic but may include evidence of pancreatitis, hypo or hyperglycemia, leukocytosis, and liver function abnormalities

• CXR may show pulmonary edema in severe cases

EKG

• Common abnormalities include ventricular dysrhythmias, torsade de pointes, and idioventricular rhythms. Heart blocks and prolongation of QTC interval are common

Treatment

• ABC’s

• Protective clothing must be worn to prevent contamination of health care workers (use neoprene or nitrile gloves instead of latex)

• Patient’s clothing must be removed and then disposed of in hazardous waste

Treatment

• Patient must be washed in copious amounts of soap and water, with possible a second washing of dilute ethanol

• Body fluids are contaminated as well

• Runoff water must be contained and disposed of in hazardous materials

Treatment

• Place patient on 100% O2, cardiac monitor and continuous pulse ox

• Suction airway as needed for bronchorrhea or emesis

• Coma, respiratory failure or seizures may necessitate intubation

Treatment

• A nondepolarizing agent should be used for intubation, as Succinylcholine is metabolized by cholinesterase. Therefore prolonged paralysis may result

Treatment

• Hypotension may need fluid boluses

• Charcoal is recommended for all ingestions

• Protect airway if you lavage, as lavage can be considered in recent or in large ingestions

• Hemodialysis has no proven value

Treatment

• Atropine and pralidoxime are antidotes• Atropine is used to reverse muscarinic and

central effects• Large amounts may be needed – the dose

is titrated until copious bronchial secretions attentuate

• Pupillary dilatation is NOT the endpoint

Atropine

• Atropine should not be withheld in the face of a tachycardia (heart rate may be the result of hypoxia)

• Initial test dose – 1 mg IV in adults, 0.01 to 0.04 mg/kg in children (but never less than 0.1mg)

Atropine

• Normally that dose should produce antimuscarinic symptoms, but if no response to trial dose, then this is indicative of an organophosphate poisoning

2-Pam

• Restores acetylcholinesterase activity by regenerating phosphorylated acetylcholinesterase

• Clinically, improves the muscarinic, nicotinic and CNS symptoms

2-Pam

• Administer as soon as possible, though is still can be administered 24 to 48 hours after exposure

• Can reverse muscle paralysis if given soon enough before aging has occurred

2-Pam

• Dose: 1-2 grams for adults and 20 to 40mg/kg – up to 1 gram in kids

• This is infused in NS over 5-10 minutes

• Can also be given IM

• A continuous infusion can be done (500 mg/hr in adults – 5-10 mg/kg/hr for kids) if paralysis does not resolve

2-Pam

• Not administered to asymptomatic patients or to patients with known carbamate exposures presenting with minimal symptoms

• Response should occur within 10-40 minutes of administration

Disposition

• Minimal exposure may just be decontamination and observation in ER for 6-8 hours

• Do not return clothing and discarded items to patient – DISCARD in hazardous waste

Disposition

• For significant poisonings – ICU

• If toxins are fat soluble, then patient may be symptomatic for weeks

• Supportive care will be needed during this time, such as respiratory support

• End point of therapy is determined by absence of signs and symptoms

Death

• Death usually occurs in 24 hours if patient is not treated

• Respiratory failure secondary to resp. muscle paralysis, CNS depression or bronchorrhea is usual cause of death

Carbamates

• Sevin, Baygon, Lannate, Carbaryl, Aldicarb

• Cholinesterase inhibitors that are structurally related to organophosphates

• Medicinal forms include physostigmine, pyridostigmine and neostigmine

Pathophysiology

• Transiently and reversibly inhibit cholinesterase

• Regeneration of enzyme occurs within minutes to hours, therefore aging does not occur

Clinical Features

• Symptoms of intoxication are similar to organophosphates, but are of shorter duration

• Carbamates do not effective penetrate into CNS, so less central toxicity and no seizures

Diagnosis

• Cholinesterase levels may return spontaneously to normal after 4-8 hours

• Measurement of cholinesterase activity generally is not useful as it will be relatively normal

Treatment

• Atropine therapy usually not needed for longer than 6-12 hours

• Avoid 2-Pam. Since irreversible binding does not occur, it is not needed, and potentially can worsen some carbamate poisonings

Organochlorines

• DDT is prototype

• Most have been restricted or banned in US due to their long half-life and toxicity

• Lindane is another common one used to treat head lice and scabies

Pathophysiology

• CNS stimulant that can be toxic after dermal, inhalation and GI exposure

• Toxicity results from repetitive neuronal discharge following the action potential due to a decrease in the sodium channel permeability

Pathophysiology

• Capable of inducing hepatic enzyme system, so the efficacy of other chemicals and drugs that use this system is reduced

Clinical Features

• Neurologic symptoms predominate

• Mild poisonings present as dizziness, malaise, HA, irritability, delirium, myoclonus and facial paresthesias. Fever is common

Clinical Features

• Severe poisonings may have seizures, coma, respiratory failure and death

• Seizures may occur early, have no prodromal syndromes and are short-lived

• Organochlorines are delivered dissolved in hydrocarbon solvents that can cause sedation, coma and pneumonitis

Clinical Features

• Sensitization of the myocardium to endogenous cathecholamines with cardiac dysrythmias can occur from both the organochlorines and the solvents

• Chronic effects from low-level exposure to chlordane include deficits in balance, reaction times and verbal recall

Diagnosis

• History is important!

• Read package label for the chemical involved and the vehicle involved

• Differential includes other causes of CNS stimulation and other insecticides

• Basic labs are not helpful but organochlorines can be detected in serum and urine by special laboratories

Treatment

• O2, intubation if needed to treat hypoxia secondary to seizures, aspiration or resp. failure

• Benzos for seizure control

• Dysrhythmia control may be indicated but avoid atropine and epinephrine as the myocardium is sensitized to endogenous catecholamines

Treatment

• Removal of clothing and washing skin with soap and water are important

• Avoid oils on skin as they promote absorption

• Charcoal and possibly gastric lavage in large recent ingestions are indicated

• Exchange resin Cholestyramine should be used in symptomatic Chlordecone exposures

Disposition

• Observed for 6 hours and admitted to hospital if signs of significant toxicity develop or if ingestion involved a hydrocarbon solvent

Pyrethrins

• Naturally occuring botanical substance found in chrysanthemum plants

• Used commonly as aerosols in insect sprays, so inhalation is most common exposure

• But also can be found in liquids and dusts in over the counter insecticides

Pathophysiology

• Block the sodium channel at the neuronal cell membrane causing repetitive neuronal discharge

• Other effects include increased nicotinic cholinergie transmission, norepinephrine release and interference with sodium-calcium exchange

Clinical Features

• Allergic hypersensitivity most common effect

• Manifest as dermatitis, asthma, rhinitis, pneumonitis and anaphylaxis

• Dermal absorption is minimal, but compounds are well-absorbed from GI tract

Clinical Features

• Skin contact may lead to tingling and burning 30 minutes after exposure, but that dissipate within 24 hours

• Allergic reactions including fatal asthma attacks have been reported

• When absorbed, metabolized rapidly in liver, so minimal systemic toxicity

Clinical Features

• Systemic symptoms would include paresthesia, hyperexcitablity, tremors, seizures, muscle weakness, respiratory failure, dizziness, HA and nausea.

• Vomiting and diarrhea seen in significant intentional ingestions

• Pulmonary edema, seizures, muscle fasciculations seen in severe poisonings

Dx and Tx

• Differential includes allergic and neurologic diseases. Lab tests are of little value

• Treatment includes removal from exposure, dermal, ocular and gut decontamination, tx of allergic manifestations and supportive care. Hydrocarbon aspiration must be avoided

Disposition

• Usually related to severity of exposure. Usually benign and hospitalization is not necessary

DEET

• In OFF! and Skintastic

• In a variety of formulations ranging in concentrations of 5% to 100%

• Large margin of safety

• Absorbed through the skin

• Neurotoxin that causes seizures in large ingestions

DEET

• Systemic toxicity manifests as restlessness, insomnia, altered behavior, confusion, CNS depression, slurred speech, ataxia, tremors, muscle cramps and hypertonia

• DEET induced hypotension and bradycardia have also been reported

DEET

• Tx includes benzos for seizures, skin decontamination with soap and water, and activated charcoal for ingestions

• Most patients recover with supportive care

Herbicides

• Chemicals used to kill weeds

• Formulations contain multiple ingredients such as solvents, surfactants and preservatives that may have their own toxic effects.

Herbicides

• In 2001, there were 9378 exposures to herbicides

• Of these, 127 were intentional

• 2594 occurring in children younger than 6

• 4 deaths from Paraquat

Chlorophenoxy Herb.

• Agent Orange was a mixture of two types (2,4-D and 2,4,5-T)

• These compounds are effective against broadleaf plants and also used as weed killers in lawns and grain crops

Pathophysiology

• Metabolic pathway unknown

• Skeletal muscle toxicity can result in resp. failure or rhabdo

• Toxicity results from dermal contact, inhalation or ingestion

Clinical Features

• After ingestion, N/V/D result

• Tachypnea may indicate pulmonary edema

• CV findings include hypotension, tachycardia and dysrhythmias

• Muscle toxicity findings include muscle tenderness, fasiculations, myotonia and rhabdo

Clinical Features

• Patient may become hyperthermic

• Peripheral neuropathy has been described in the recovery phase and in chronic exposure

Diagnosis

• Based on history• Ancillary tests nonspecific but may

demonstrate a metabolic acidosis and evidence of hepatorenal dysfunction

• Toxin levels not immediately available• Myoglobinuria and elevated CPK indicate

rhabdo• Differential includes other causes of

myopathy

Treatment

• Supportive

• Decontamination measures and resp. support

• Alkalinization is suggested but not proven to increase the elimination of these compounds

• Treat the rhabdo

Disposition

• Severe toxicity and serious complications are not common

• Since effects usually appear within 4-6 hours, patients with mild symptoms can be observed and discharged after that time

• Significant toxicity warrants admission

Bipyridyl Herbicides

• Paraquat and diquat

• Ingestion responsible for most deaths

• Death has also been reported after transdermal exposure, ingestion and inhalation

Pathophysiology

• Severe local irritant and devastating systemic toxin

• Ingested, it is absorbed rapidly

• Plasma concentrations peak within 2 hours of ingestion

• Distributed to most organs, with kidneys and lungs having the highest concentration

Pathophysiology

• Acute exposure causes liver and renal necrosis, that is followed within a few weeks by pulmonary fibrosis

• Accumulated in the alveolar cells of the lungs, where it is transformed into a reactive oxygen species – a superoxide radical

Pathophysiology

• Responsible for lipid peroxidation that leads to degradation of cell membranes, cell dysfunction and cell death

• Two phases – Initial destructive phase causes inflammatory cells and hemorrhage, but these changes may be reversible

Pathophysiology

• Second proliferative phase involves fibrosis in the interstitium and alveolar spaces

• Myocardial injury and necrosis of the adrenals may occur

Clinical Features

• Caustic effects produce local skin irritation and ulceration, as well as corneal injury in eye exposures

• Upper Resp Tract exposure may result in mucosal injury and epistaxis

• Inhalation may lead to cough, dyspnea, chest pain, pulmonary edema and hemoptysis

Clinical Features

• Ingestion causes gastrointestinal mucosal lesions and ulcerations

• Hypovolemia occurs from GI fluid losses and decreased PO intake

• CV collapse may occur early in intoxication

• Seizures, GI perforation and hemorrhage and hepatic failure may occur

Clinical Features

• Massive ingestions lead to multisystem failure and death within a few days

• Renal and hepatocellular necrosis develop b/w the 2nd and 5th days, with pulmonary fibrosis leading to hypoxemia 5 days to several weeks later

Diagnosis

• History is important

• Qualitative and quantitative analyses for paraquat in urine and blood can assist you

• Nomograms used to predict survival based on plasma paraquat concentration and time of ingestion

• A 10 hour level greater than 0.4 mg/L carries a high probability of death

Diagnosis

• Chemistry abnormalities may reflect multiorgan necrosis

• Hypokalemia may be present

• CXR show pneumonmediastinum or pneumothroax in the case of corrosive rupture of esophagus

• EGD should be performed to identify the extent of mucosal lesions

Treatment

• Early and vigorous decontamination!

• Any exposure to paraquat is a medical emergency with hospitalization indicated even if patient is asymptomatic

• Attempt should be made to discourage superoxide radical formation by using low inspired oxygen to produce a hypoxemia to reduce pulmonary injury

Treatment

• Using oxygen mixtures (FiO2 <21%) with positive pressure ventilation reduces pulm toxicity in experimental models and may be of therapeutic benefit

• Clothing removed and skin decontaminated with soap and water, but do not cause further abrasions that might increase systemic absorption

Treatment

• Ocular irrigation with copious amounts of water or saline must take place

• Fluid and electrolyte losses need to be replaced

• Treat pain (from lesions) with opioids

• Emesis is common but gastric lavage via orogastric tube is recommended despite risk of perf.

Treatment

• Gut decontamination is indicated as well

• Charcoal (1-2 g/kg), diatomaceous Fuller’s earth (1-2 g/kg in 15% aqueous suspension) or bentonite (1-2 g/kg in a 7% aqueous slurry)

• Repeat every 4 hours

• Sorbitol (70%) using 2ml/kg cathartic should be administered initially

Treatment

• Charcoal hemoperfusion is known to remove paraquat and should be instituted as soon as possible and continued for 6-8 hours

• Support includes airway, maintaining intravascular volume, monitor vitals and ABG’s, pain relief, tx of renal failure and tx of infection

• MAINTAIN RENAL FUNCTION

Disposition

• Attempt to determine prognosis

• Mortality rate from ingestion is as high as 75 %

• Recovery is usually without sequelae

• Ingestions of 20-40mg/kg usually results in death in 5 days to several weeks

Disposition

• If more than a mouthful (50mg/kg) is ingested, death occurs within 72 hours

Urea-Substituted Herb.

• Chlorimuron, diuron, fluometron, isopturon

• Low systemic toxicity

• Methemoglobinuria may occur

• Tx includes decontamination, supportive care and tx with methylene blue

Organophosphorous Herb.

• Glyphosate (Roundup) is widely used

• Clinical effects include mucous membrane irritation and erosions, widespread organ dysfunction and refractory CV collapse

• Tx options are limited to charcoal and supportive care

Rodenticides

• In 2001, there were 19,294 rodenticide exposures

• Long-acting superwarfarin agents accounted for 16,423 of these, most of which were in children less than 6 years of age

• 2 deaths, but none from the superwarfarins

Rodenticides

• Nonanticoagulants– High toxicity

• Arsenic• Barium• Phosphorous• Strychine

– Moderate toxicity -Naphthylthiourea

– Low Toxicity• Red Squill• Norbormide• Bromethalin

Rodenticides

• Anticoagulants– Warfarin types– Superwarfarins

– Single ingestions of Warfarin types are insignificant poisonings and do not usually cause bleeding problems

– Half-life of some superwarfarins are 120 days and can cause problems for weeks

Clinical Approach

• Identifying product name is essential for management

• Specific odors or CNS, cardiopulmonary, GI, muscle or hemorrhagic manifestations may suggest a specific toxin

Disposition

• Given the low frequency of physician experience with these types pf exposures, poison centers or toxicology consults must be used

• Threshold for hospital admission should be low

Anticholinergic Toxicity

Chapter 183

Feb. 23, 2006

Anticholinergics

• Should always be considered in patients that present to ED with unexplained mental status changes

• Antihistamine overdose is most common presentation

• In children, unintentional ingestion of just a few pills can result in significant toxicity

Anticholinergics

• In elderly, therapeutic doses of certain pharmaceuticals may produce anticholinergic effects

• Intentional ingestions by teenagers is not uncommon – Alkaloid plants are abused for their hallucinogenic effects and group ingestions may result in multiple patients in your ED

Pharmacologic Properties

• Anticholinergic refers to drugs and plant toxins that act as muscarinic receptor antagonists

• Drug absorption can occur after ingestion, smoking or ocular use

• Because these toxins slow GI motility, peak clinical effects are often delayed

Anticholinergics

• Antihistamines

– Benadryl

– Dramamine

• AntiParkinsonian

– Cogentin

• Antipsychotics

– Thorazine

– Mellaril

– Clozapine

• Antispasmodics

– Bentyl

• Plants

– Deadly nightshade

– Jimsonweed

– Mandrake

• Skeletal Muscle Relaxants

– Norflex

– Flexeril

• Cyclic antidepressants

– Elavil

– Tofranil

– Sinequan

– Prozac

Clinical presentations

• Mnemonic heaven…– Dry as a bone– Red as a beet– Hot as Hades– Blind as a bat– Mad as a hatter– Stuffed as a pipe

Clinical Presentations

• Dry skin and dry mouth as a result of decreased sweat gland and salivary gland secretions

• Decreased bowel sounds as a result of decreased GI motility

• Palpable bladder secondary to urinary retention

Clinical Presentations

• Tachycardia (120-160)

• Dilated pupils, though onset may be delayed 12-24 hours

• Delirium is common, with staccato speech pattern and difficult to comprehend speech

• Visual hallucinations, repetitive picking at bed clothes or imaginary objects have been observed

Clinical Presentations

• Agitation-induced hyperthermia, esp when patient now has decreased sweating. This hyperthermia may result in multi-system organ dysfunction, resulting in liver, kidney and brain injury and coagulopathy.

• In some instances these changes are irreversible

Clinical Presentations

• Central excitation and depression may both occur “agitated depression”

• Depressive features include lethargy, somnolence and coma

• Fatalities associated with overdose are characterized by severe agitation, status epilepticus, hyperthermia, wide-complex tachydysrhythmias and CV collapse

Lab Evaluation

• Routine labs (incl. lytes, glucose and pulse ox) should be checked

• In most cases, these tests should be normal

• Limited UDS (drug screen) does not detect anticholinergics, though some pick up TCA’s

Differential

• Viral Encephalitis

• Reye Syndrome

• Head Trauma

• ETOH withdrawl

• Postictal state

• Neuroleptic malignant syndrome

• Acute Psychiatric disorder

Treatment

• Observation, monitoring and support

• Temperature monitoring essential

• GI decontamination may be warranted with charcoal, even after >1 hour post ingestion as decreased GI motility may still allow charcoal to help

Treatment

• IV Bicarb to tx wide complex tachydysrhythmias

• Avoid class Ia agents as they have their own sodium channel blockade effect

Treatment

• Major challenge is treating agitated patient

• Inadequate sedation may lead to worsening hyperthermia, rhabdo and injury

• Physical restraints may be needed, sedation is strongly recommended. Prolonged restraints may lead to further complications

Treatment

• IV benzo’s such as lorazepam (2.5 mg IV) is appropriate first-line therapy

• Avoid phenothizines because of their anticholinergic effects

Treatment

• Use of Physostigmine to reverse anticholinergic toxicity remains controversial

• Physostigmine is a reversible acetylcholinesterase inhibitor – crosses the blood-brain barrier

• This results in acetylcholine accumlation that reverses anticholinergic effects

Treatment

• But may aggravate dysrhythmias and seizures and must be used with caution

• If used to treat drug overdoses that have sodium channel blockade (such as TCA’s) can cause bradycardia and asystole

• Patients without clear evidence of anticholinergic poisoning should not receive physostigmine

Treatment

• Physostigmine can be considered in cases of severe agitation and delirium esp. in cases necessitation physical restraints for control no responsive to benzos

• Dose is 0.5 to 2.0 mg IV, slowly administered over 5 mintues

• When effective, a decrease in agitation may be seen in 15-20 minutes

Treatment

• Because of rapid elimination, may need to repeat doses every 30-60 minutes

• Patients should be on a cardiac monitor and observed for signs of cholinergic excess (SLUDGE – remember?)

• Contraindications to physostigmine include asthma, cardiac conduction disturbances, suspected Na channel poisoning, or non-pharmacologically mediated intestinal or bladder obstruction

Disposition

• Mild symptoms can be discharged after 6 hours of observation, if their symptoms have resolved

• More symptomatic patients require admission for at least 24 hours

• Because the half-life of physostigmine is shorter than the half-life of many anticholinergics, and the reversal effect may dissipate, resulting in recurrent toxicity, admission for continued observation is warranted in patients who received physostigmine