Organochlorine Pesticide Toxicity
Practice Essentials
Chlorinated hydrocarbon (organochlorine) insecticides, solvents, and fumigants are widely used around the world. This class of chemicals comprises a variety of compounds containing carbon, hydrogen, and chlorine and are largely banned in North America and Europe, but are used extensively in many developing nations. In addition, these chemicals may still be found in storage in the United States; thus, exposure remains possible.
The toxicity of organochlorine (OC) pesticides varies according to their molecular size, volatility, and effects on the central nervous system (CNS). In general, they cause either CNS depression or stimulation, depending upon the agent and dose. [1]
Signs and symptoms
CNS excitation and depression, typically abrupt in onset, are the primary clinical effects of acute organochlorine toxicity; therefore, patients may present with any of the following:
Initial euphoria with auditory or visual hallucinations and perceptual disturbances
Seizures
Agitation, lethargy, or unconsciousness
Other signs and symptoms include the following:
Pulmonary - Cough, shortness of breath
Dermatologic - Skin rash
Gastrointestinal - Nausea, vomiting, diarrhea, and abdominal pain
Nervous system - Headache, dizziness, or paresthesias of the face, tongue, and extremities
Ingestion produces the following manifestations:
Nausea and vomiting
Confusion, tremor, myoclonus, coma, and seizures
Respiratory depression or failure
Unusual odor - Toxaphene may have a turpentine-like odor; endosulfan may have a sulfurous odor
Skin absorption or inhalation produces the following manifestations:
Ear, nose, and throat irritation
Blurred vision
Cough
Acute lung injury
Dermatitis
Long-term occupational exposure to organochlorine pesticides may result in various nonspecific symptoms, including headaches, nausea, fatigue, muscle twitching, and visual disturbances. In addition, chronic exposure to these agents may be associated with the development of blood dyscrasias, including aplastic anemia and leukemia in humans (inconclusive).
Other manifestations of chronic exposure are as follows:
Anorexia
Hepatotoxicity
Renal toxicity
CNS disturbances
Skin irritation
.Diagnosis
The history of exposure is the most important piece of information. Laboratory studies may include the following:
Rapid bedside glucose fingerstick test
Electrolytes
Renal panel
Liver function tests
Creatine phosphokinase (CPK)
Lactate
Arterial or venous blood gas
Urinalysis
Urine pregnancy testing in women of childbearing age
Electrocardiography
Screening serum and urinary toxicology panels, particularly acetaminophen and salicylate levels if intentional exposure is suspected
Chlorinated hydrocarbon levels (can be measured, but not clinically helpful nor routinely available)
Possible abnormal findings by organ system are as follows:
Pulmonary - Increased A-a gradient, hypoxemia (see the A-a Gradient calculator)
Cardiovascular - Sinus tachycardia or bradycardia, QTc prolongation, nonspecific ST-segment changes
Gastrointestinal - Transaminitis and hyperbilirubinemia
Hematologic - Leukocytosis and prolonged activated partial thromboplastin time (aPTT)
Renal - Acidemia, azotemia, creatinine elevation, hyperkalemia
See Workup for more detail.
Treatment
Supportive care and observation for signs of end-organ damage (eg, CNS, heart, lung, liver) are the mainstays of therapy. No specific antidotes are available for organochlorine poisoning.
Decontamination may be indicated to prevent continued absorption, as well as exposure of health care personnel. For dermal decontamination, remove clothing and wash skin with soap and water. This is best performed in the field.
Observe patients with an apparent nonsignificant and nontoxic exposure in the ED for 6-8 hours. If any signs or symptoms of toxicity develop during that time, admit the patient to the hospital. Intensive care unit admission is indicated for patients with significant exposure or with signs and symptoms of intoxication.
Repeated assessments of the patient’s ABCs and vital signs are of extreme importance in cases of acute poisoning. In particular, airway protection must be assured.
Regardless of the route of exposure, consider multiple-dose activated charcoal (MDAC) because it may enhance fecal elimination by interrupting the biliary-enterohepatic and enteroenteric recirculation of the toxin. Cholestyramine may be used to bind these highly lipophilic agents.
See Treatment and Medication for more detail.
Background
Chlorinated hydrocarbons can be highly toxic, and the overwhelming majority have been universally banned because of their unacceptably slow degradation and subsequent bioaccumulation and toxicity. [2] Among the more notable examples is dichlorodiphenyltrichloroethane (DDT). The synthesis of DDT by the Swiss chemist Paul Müller in the late 1930s, and the subsequent demonstration of its effectiveness as an insecticide, won Müller the 1948 Nobel Prize in Physiology or Medicine, [3] but DDT was banned in the United States in 1972. [4]
Pathophysiology
Organochlorines can be separated into 5 groups, as follows:
DDT and analogues (eg, dicofol, methoxychlor)
Hexachlorocyclohexane (ie, benzene hexachloride) and isomers (eg, lindane, gamma-hexachlorocyclohexane)
Cyclodienes (eg, endosulfan, chlordane, heptachlor, aldrin, dieldrin, endrin, isobenzan)
Chlordecone, kelevan, and mirex
Toxaphene
Organochlorines are well absorbed orally and by inhalation. Transdermal absorption is variable. For example, DDT is poorly absorbed transdermally, whereas cyclodienes have significant transdermal absorption rates. [5] Cyclodienes have high absorption levels when taken orally, as in the case of food contamination with these pesticides. [6] Lindane is known to be absorbed after topical application, but oral ingestions are not rare. [7] Young age, malnourishment, and frequent exposure increases the risk for toxicity. [8]
Organic chlorines are strongly lipid soluble and sequester in body tissues with high lipid content, such as the brain and liver. Consequently, blood levels tend to be much lower than fatty tissue levels. [5] The lipophilic tendency of organochlorines accounts for prolonged systemic effects in overdose. The half-life of DDT has been measured in months or years, whereas other organic chlorines are metabolized faster; for example, lindane has a half-life of 21 hours. [9]
Mechanism of toxicity
Toxicity in humans is largely due to stimulation of the CNS. Cyclodienes, hexachlorocyclohexanes, and toxaphene predominantly are gamma aminobenzoic acid (GABA) antagonists and inhibit calcium ion influx, but also may inhibit calcium and magnesium adenosine triphosphatase (ATPase). The resulting accumulation of calcium ions at neuronal endplates causes sustained release of excitatory neurotransmitters. [10, 11]
DDT affects potassium and voltage-dependent sodium channels. These changes can result in agitation, confusion, and seizures. Cardiac effects have been attributed to sensitization of the myocardium to circulating catecholamines.
Some of the more volatile organochlorines can be inhaled while in vapor form or swallowed while in liquid form. Inhalation of toxic vapors or aspiration of liquid after ingestion may lead to atelectasis, bronchospasm, hypoxia, and a chemical pneumonitis. In severe cases, this can lead to acute lung injury, hemorrhage, and necrosis of lung tissue. In liquid form, they are easily absorbed through the skin and GI tract.
Highly toxic organochlorines include:
Aldrin
Dieldrin [12]
Endrin [13]
Endosulfan [14, 15]
Moderately toxic organochlorines include:
Chlordane
DDT
Heptachlor
Kepone
Lindane
Mirex
Toxaphene
Epidemiology
Organochlorine pesticides are now only rarely used in the developed world, and domestic poisonings have become correspondingly rare. Lindane is still used as a second-line topical prescription treatment for head lice and scabies. Adults are most likely to have serious intentional poisonings, and children are most likely to have unintentional poisonings.
The 2020 Annual Report of the American Association of Poison Control Centers' National Poison Data System lists pesticide exposure as the eleventh most common substance involved in human exposures in the United States. [16] In 2020, 70,831 single pesticide exposures were reported; 138 single explosure to chlorinated hydrocarbon insecticides and an additional 75 single exposures in combination with other insecticides were reported; 22 cases had a moderate or major effect outcome but no deaths were reported. [16]
Acute poisoning and fatality caused by organochlorine exposure is rare. DDT was banned by the US Environmental Protection Agency (EPA) in 1972. The EPA and manufacturers of organochlorine pesticides agreed to halt sales of organochlorine pesticides in 1987 after a partial ban in 1976. [4] All use of toxaphene was banned in 1990.
Despite a ban on sales, organochlorines may still be found in storage in the United States; thus, exposure is still possible. Toxaphene can be transported in the air at long distances and can persist in air, soil, and water for years.
Although widespread use of organochlorine insecticides has been banned in North America and Europe, these chemicals are used extensively in many developing nations, for example, DDT is still in indoor use in malaria-afflicted areas. [4] Organochlorine poisoning accounts for only a small fraction of pesticide poisoning, but the incidence varies from 1.8% of all poisonings in South Korea to 13.3% in some parts of India. [17, 18] A study of contamination in the Brazilian population showed adverse effects on hematopoietic tissue and the liver. [19]
Prognosis
The prognosis in patients exposed to organochlorine compounds depends on the amount and type of exposure. Pulmonary fibrosis can occur after significant aspiration. Acute respiratory distress syndrome (ARDS) may develop.
Toxic doses widely vary. The fatal dose in humans is unknown; data from nonfatal cases suggest that a dose of approximately 10 mg/kg can cause convulsions. An oral median lethal dose (LD50) is higher than 50 mg/kg in animal studies. The estimated approximate minimum lethal dose for humans is 2-7 g. With adequate decontamination and supportive care, patients generally recover from acute exposure to their previous functional level.
Studies have suggested a long-term risk of cancer [20, 21] , type 2 diabetes [22] and neurodegenerative diseases. [23, 24] However, these risks are more attributable to chronic exposure. Analysis of National Health and Nutrition Examination Surveys (NHANES) data did find that higher exposure to beta-hexachlorocyclohexane is associated with increased all-cause mortality and higher exposure to four other organochlorine pesticides is associated with increased non-cancer, non-heart/cerebrovascular disease mortality in US adults 60 years or older. [25]
Toxaphene interferes directly or indirectly with fertility and reproduction in rodents (testicular degeneration and endocrine changes). Toxaphene is teratogenic in mice and rats at doses that result in overt maternal toxicity. Also, tumors arise in the liver (eg, hepatomas) and renal tubules of chronically exposed animals.
Patient Education
Refer patients and their families to public health authorities for education regarding the use, storage, and proper disposal of pesticides. Educate patients about proper medical discharge instructions regarding acute and potential chronic signs and symptoms that are observed in toxaphene and organochlorine toxicity. Document this education.
Discuss possible long-term risk of breast cancer with female patients. Organochlorine pesticides and metabolites accumulate in breast tissue and milk. An experienced laboratory should analyze breast milk of pregnant or lactating women for toxic organochlorines, associated product contaminants, and their metabolites. [26]
For unknown pesticide exposures, information is available at the Extension Toxicology Network (EXTOX-NET). The National Pesticide Information Center is available 9:30 am to 7:30 pm Eastern Standard Time at 1-800-858-7378.
Clinical Presentation
History
The history of exposure to an organochlorine pesticide is the most important piece of information to obtain. In many cases the exact history will not be known, and efforts to identify the offending agent should be made. Information on the toxin involved is valuable because organochlorine exposure may produce the same clinical manifestations as other poisons that are much more commonly available, particularly in the United States. Furthermore, there should be concern about inadvertent exposure to healthcare providers, as well as to laypeople in contact with the patient.
At a minimum, the history should include the following:
Prior medical and psychiatry history
Nonprescription drugs used
Natural or herbal preparations used
Allergies to medications
Patient activity for that day of exposure
Occupational history, including farming; field work; and chemical or pesticide manufacturing, handling, or application
Pest control use
Location in relation to industrial facilities or waste sites
Hobbies (eg, gardening)
If possible, obtain the product in its original container. Review the label and contact the poison control center. Save the sample for possible testing and identification. Usually, testing has to be performed at an outside laboratory and has no immediate clinical impact on the patient's treatment.
United States law requires that pesticide package labels contain certain information regarding product classification and toxicity, which is based on animal oral studies of median lethal dose. The following are classifications for the toxic categories:
Danger - High toxicity
Warning - Moderate toxicity
Caution - Low toxicity
No signal word - Safe
Onset of symptoms is characteristically abrupt. Central nervous system (CNS) excitation and depression are the primary effects observed in acute organochlorine toxicity; therefore, the patient may appear agitated, lethargic, intoxicated, or may even be unconscious. Initial euphoria with auditory or visual hallucinations and perceptual disturbances are common in the setting of acute toxicity.
Organochlorines lower the seizure threshold, which may precipitate seizure activity. Strong external stimuli and reflex hyperexcitability may precipitate muscle fasciculations and tonic spasms, which may evolve into seizures.
Patients may have pulmonary complaints or may be in severe respiratory distress. Cardiac dysrhythmias may complicate the initial clinical presentation.
Other symptoms include the following:
Pulmonary - Cough, shortness of breath
Dermatologic - Rash
Gastrointestinal - Nausea, vomiting, diarrhea, and abdominal pain
Nervous system - Headache, dizziness, or paresthesias of the face, tongue, and extremities
Physical Examination
Because of the high lipid solubility, duration of toxicity can be prolonged. Life-threatening complications are seizures secondary to prolonged CNS stimulation and consequent hypoxia.
Physical examination findings vary by type of exposure, as follows:
Ingestion
Skin absorption or inhalation
Chronic exposure
Ingestion produces the following manifestations:
Nausea and vomiting
Confusion, tremor, myoclonus, coma, and seizures
Respiratory depression or failure
Unusual odor - Toxaphene may have a turpentine-like odor; endosulfan may have a sulfurous odor
Skin absorption or inhalation produces the following manifestations:
Ear, nose, and throat irritation
Blurred vision
Cough
Acute lung injury (ALI)
Dermatitis
Long-term occupational exposure to organochlorine pesticides may result in various nonspecific symptoms, including headaches, nausea, fatigue, muscle twitching, and visual disturbances. In addition, chronic exposure to these agents may be associated with the development of blood dyscrasias, including aplastic anemia and leukemia in humans (inconclusive).
Other manifestations of chronic exposure are as follows:
Anorexia
Hepatotoxicity
Renal toxicity
CNS disturbances
Differential Diagnoses
Diagnostic Considerations
Except in patients with clearly documented acute exposure, a broad differential diagnosis should be considered. Alternative explanations for symptoms may include other toxidromes, underlying medical conditions, and trauma. Other problems to consider may include the following:
CNS stimulant ingestions and overdose
Camphor toxicity
Strychnine toxicity
Picrotoxin toxicity
Sodium monofluoroacetate (SMFA) toxicity
Hypoxemia
Idiopathic epilepsy
Differential Diagnoses
Plant Poisoning, Herbs
Plant Poisoning, Hypoglycemics
Toxicity, Carbon Monoxide
Toxicity, Hydrogen Sulfide
Toxicity, Organophosphate and Carbamate
Toxicity, Rodenticide
Toxicity, Terpene
Workup
Approach Considerations
The history of exposure is the most important piece of information. Laboratory studies may include the following:
Rapid bedside glucose fingerstick test
Electrolytes
Renal panel
Liver function tests
Creatine phosphokinase (CPK)
Lactate
Arterial or venous blood gasUrinalysis
Urine pregnancy testing in women of childbearing age
Electrocardiography
Screening serum and urinary toxicology panels, particularly acetaminophen and salicylate levels if intentional exposure is suspected
Chlorinated hydrocarbon levels (can be measured, but not clinically helpful nor routinely available)
Plasma and red blood cell cholinesterase testing may be considered in cases in which organophosphorus compound co-exposure may have occurred or if offending toxicant has not been determined and the patient presents with signs or symptoms consistent with a cholinergic toxidrome.
Possible abnormal findings by organ system are as follows:
Pulmonary - Increased alveolar–arterial (A-a) gradient, hypoxemia (see the A-a Gradient calculator)
Cardiovascular - Sinus tachycardia or bradycardia, QTc prolongation, nonspecific ST-segment changes
Gastrointestinal - Transaminitis and hyperbilirubinemia
Hematologic - Leukocytosis and prolonged activated partial thromboplastin time (aPTT)
Renal - Acidemia, azotemia, creatinine elevation, hyperkalemia
Chest radiography may be indicated in the case of aspiration or acute lung injury. An abdominal radiograph may show evidence of radiopaque chlorinated pesticide. [27] When the history of exposure is unclear, a head CT scan/lumbar puncture should be considered to rule out a central nervous system process or infection as a cause of seizures and altered mental status.
If necessary, gas chromatographic analytical studies of serum, adipose tissue, urine, and breast milk can be considered for documentation of exposure. For occupational purposes, performing adipose tissue biopsy testing for estimating total body burden of an exposed population is possible. This has no application in acute treatment of an individual exposed patient.
For the emergency department clinician, the above studies are unlikely to be of any acute clinical value because the likelihood of a rapid test result is small. However, obtaining samples for these examinations may be valuable for the extended-term evaluation and treatment of the patient.
Postmortem Forensic Examination
In a postmortem forensic examination, brain analytical studies are warranted because severity of toxicity correlates with CNS concentration of these insecticides. Therefore, when a patient's death possibly is caused by acute or chronic pesticide exposure, alert the coroner so that appropriate safety issues may be addressed. This action is especially important in occupationally related cases.
Treatment & Management
Approach Considerations
Supportive care and observation for signs of end-organ damage (eg, central nervous system [CNS], heart, lung, liver) are the mainstays of therapy. No specific antidotes are available for organochlorine poisoning. Decontamination may be indicated to prevent continued absorption, as well as exposure of health care personnel. For dermal decontamination, remove clothing and wash skin with soap and water. This is best performed in the field.
Observe patients with an apparent nonsignificant and nontoxic exposure in the emergency department (ED) for 6-8 hours. If any signs or symptoms of toxicity develop during that time, admit the patient to the hospital. Intensive care unit admission is indicated for patients with significant exposure or with signs and symptoms of intoxication.
Prehospital Care
Attend to the ABCs (airway, breathing, circulation). Protect the airway at all times.
Remove the patient from source of exposure and prevent contamination of others. Consider skin decontamination by washing with soap and water and removing clothing (place in plastic bags) as early as possible. Skin decontamination is performed best in the field.
Do not induce emesis, because the patient may have a sudden change in mental status and could aspirate gastric contents. Avoid strong external stimuli to the patient, which may precipitate convulsions. Initiate cooling measures if the patient is hyperthermic.
Do not forget that other persons still may be at risk of intoxication. Medically evaluate all of these persons as soon as possible. With massive exposure or multiple victims, contact a hazardous materials (HAZMAT) team for assistance.
Emergency Department Treatment
Repeated assessments of the patient’s airway, breathing, and circulation (ABCs) and vital signs are of extreme importance in cases of acute poisoning. In particular, airway protection must be assured. Consider early rapid-sequence intubation to facilitate aggressive benzodiazepine use.
Seizures may begin without any prodromal signs or symptoms. If the patient is paralyzed after intubation, electroencephalographic monitoring is warranted. Termination of seizure activity should be attempted using traditional treatment algorithms, starting with benzodiazepines and progressing if necessary to phenytoin or fosphenytoin, propofol, and barbiturates. Rhabdomyolysis should be considered in patients with prolonged convulsions or those who have acute renal failure with or without hyperkalemia.
Continuous cardiac monitoring is indicated. Use epinephrine and sympathomimetic amines with caution because dysrhythmias can be induced, as a result of increased myocardial sensitization to catecholamines. Use of beta-blockers is reported to control ventricular dysrhythmias because of sensitized myocardium. If the patient is hypotensive and unresponsive to fluids, intravenous administration of a pure alpha-adrenergic agonist agent (eg, phenylephrine) is the therapy of choice.
In cases of ingestion, do not induce emesis. Insertion of a nasogastric tube for stomach evacuation is controversial; it may induce vomiting with subsequent aspiration. Carefully perform orogastric lavage with suction, especially for recent liquid ingestion. Always secure the airway well before executing lavage. If nasogastric suction is used, a small-bore tube should be used.
Regardless of the route of exposure, consider multiple-dose activated charcoal (MDAC) because it may enhance fecal elimination by interrupting the biliary-enterohepatic and enteroenteric recirculation of the toxin. MDAC should be used with caution because patients are at increased risk for seizures [28] and consequent aspiration. Aqueous-based activated charcoal should be used, as sorbitol-based activated charcoal may induce vomiting.
Cholestyramine may be used to bind these highly lipophilic agents. Cholestyramine reduces reabsorption and retains bound agent in the GI tract for fecal elimination. [29] In patients who have ingested chlordecone, multiple repeated doses of cholestyramine can be administered to interrupt enteroenteric and enterohepatic recirculation. [30]
Sucrose polyester (Olestra) has also been shown to increase excretion of fat-soluble organic chlorine chemicals. [31] Whole-bowel irrigation may be indicated, but it is not without risk and so should be performed only at the discretion of a medical toxicologist or a poison control center. Induced diuresis, hemodialysis, and hemoperfusion have not been shown to be effective enhanced elimination techniques.
If liver abnormality or necrosis is suspected (eg, because of elevated serum levels of liver enzymes), administration of N-acetylcysteine (NAC) may in theory prevent irreversible hepatic injury. Generally, the only significant adverse event associated with oral use of NAC is pulmonary aspiration; therefore, ensure proper protection of the airway.
In contrast to organophosphate poisoning, atropine and oximes are not established antidotes for organochlorine toxicity. [32] The use of steroids or prophylactic antibiotics for aspiration is controversial and cannot be recommended because of a lack of evidence for their efficacy. External cooling may be used for hyperthermia.
Arrange follow-up care before discharge so that the patient may be monitored for possible long-term sequelae. Arrange for patient education on proper storage and use of pesticides. Survey for ongoing exposure in the home and work environment is important.
Obtain a psychiatric evaluation, if warranted, before discharge. Explore the possibility of child, elder, or vulnerable adult abuse or neglect.
Consultations
In all cases, consult with the regional poison control center for information regarding the speciof fic ingestion. If possible, consult with a medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine). In cases of occupational exposure, alert public health authorities to assist in prevention of further exposures in a potentially unsafe work environment.
Exposure may be caused by a work-related incident. Legally, the physician may be required to file a report to the state or local health department. Even if not legally required, reporting the exposure to prevent further cases from occurring may be wise. Organochlorines (with the exception of lindane) are banned by the US Environmental Protection Agency, so any use of these compounds is illegal.
Medication
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications. No specific antidotes are available for organochlorine poisoning; rather, the medications used in these cases include gastrointestinal decontaminants, beta-blockers, vasopressors, and benzodiazepines and other anticonvulsants.
Antidotes
Class Summary
These agents adsorb GI toxins, which are then fecally excreted, thus minimizing systemic absorption. They may not adsorb hydrocarbons and other toxins. They are beneficial only if administered within 1-2 h of ingestion.
Besides adsorbing toxins, activated charcoal creates a diffusion gradient in the GI circulation (ie, a "sink" effect), which draws the absorbed drug into the GI tract for binding and elimination. Administer after careful risk-to-benefit consideration, and most likely after consultation with a poison control center or a medical toxicologist.
Activated charcoal is an emergency treatment for poisoning caused by drugs and chemicals. The network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. It does not dissolve in water.
For maximum effect, administer within 30 minutes of ingesting poison. Multiple-dose activated charcoal (MDAC) may be administered at 10-20 g q2-4h without a cathartic.
Bile acid sequestrants
Class Summary
These binding agents are used in the treatment of hypercholesterolemia and have been noted to bind certain lipid-soluble substances, as well as substances that are normally recirculated through the biliary-enterohepatic and enteroenteric system.
Binding resin binds secreted insecticide and metabolites, reducing reabsorption and retaining the bound agent in the lumen of the intestinal tract. Also, by binding bile salts and, therefore, reducing formation of emulsions, binding resin minimizes uptake of these highly lipid-soluble agents.
Cholestyramine is a nonabsorbable bile acid–binding anion exchange resin that forms a nonabsorbable complex with bile acids in the intestine, which in turn inhibits enterohepatic reuptake of intestinal bile salts.
Beta-Blockers
Class Summary
Ventricular dysrhythmias may respond to beta-adrenergic blockade therapy. In contrast, if mixed adrenergic stimulation is highly suspected acutely, do not use beta-blockers because of the possibility of developing deleterious unopposed alpha-adrenergic stimulation.
This category of drugs has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In the setting of myocardial ischemia, beta-blockers have antiarrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.
Consider an alpha-agonist, such as phenylephrine, for the treatment of hypotension that does not respond to fluid replacement.
Propranolol is a nonselective beta- blocker with membrane depressant activity. Maximum beta-blockade is achieved with a dose of approximately 0.2 mg/kg.
Esmolol is a short-acting cardioselective beta-adrenergic blocker with no membrane-depressant activity. It is administered intravenously.
Alpha Adrenergic Agonists
Class Summary
These agents increase peripheral vascular resistance and blood pressure. They decrease cardiac output and renal perfusion.
Phenylephrine is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body and increases peripheral venous return. It is useful in treating hypotension. Theoretically, using pure alpha-agonists for hypotension is better because of sensitized myocardium.
Anxiolytics, Benzodiazepines
Class Summary
Mainstay of treatment for hydrocarbon insecticide–induced seizures.
A sedative hypnotic with rapid onset of effects and a relatively long half-life, lorazepam is the drug of choice for seizure control in patients with organochlorine-induced seizures. The rate of injection should not exceed 2 mg/min. Lorazepam may be administered intramuscularly if intravenous access cannot be obtained.
By increasing the action of gamma aminobenzoic acid (GABA), a major inhibitory neurotransmitter in the brain, lorazepam may depress CNS function at all levels, including limbic and reticular formation. Monitor the patient's blood pressure after administering a dose of lorazepam and adjust subsequent doses as necessary.
Midazolam is used as alternative agent for termination of refractory status epilepticus. Because it is water soluble, midazolam takes approximately 3 times longer than diazepam to reach peak effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating a procedure or repeating the dose. Midazolam may be administered intramuscularly if vascular access cannot be obtained.
Diazepam depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. If convulsions persist despite treatment with diazepam, administer an alternative anticonvulsant.
Anticonvulsants, Hydantoins
Class Summary
Phenytoin and fosphenytoin are second-line agents for acute control of seizures. The antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate, so concomitant administration of an IV benzodiazepine will usually be necessary to control seizures.
Phenytoin must be administered slowly and therefore takes longer to enter the brain than benzodiazepines. However, it has the advantage of a long duration of action and can be administered orally after acute illness.
Phenytoin is not water-soluble and must be solubilized in a propylene glycol carrier with a pH of 12 to prepare an IV form. Therefore, it cannot be given more rapidly than 50 mg/min without risk of significant hypotension and cardiac arrhythmias. It also carries the major risk of potential irritation at the IV site and vascular compromise of the infused limb. Therefore, its use in status epilepticus should be avoided if possible.
Fosphenytoin is a diphosphate ester salt of phenytoin that acts as a water-soluble prodrug of phenytoin. After administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
To avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express the dose as phenytoin sodium equivalents (PE). Although it can be administered IM, the IV route is route of choice and should be used in emergency situations.
This drug carries an FDA Black Box warning cautioning against exceeding a rate of administration of 150 mg PEs per minute, due to risk of severe hypotension and cardiac arrhythmias.
Anticonvulsants, Barbiturates
Class Summary
These agents have direct effects on the benzodiazepine–GABA-A–chloride receptor complex in enhancing chloride flux.
Pentobarbital is a short-acting barbiturate that interferes with transmission of impulses from the thalamus to the cortex. It has sedative, hypnotic, and anticonvulsant properties. It is a second-line drug for treatment of drug-induced seizures.
General Anesthetics, Systemic
Class Summary
Propofol, an intravenous anesthetic agent, is active on the glutamate and GABA-A receptors, similar to alcohol itself, whereas benzodiazepines are active only against the GABA receptors. Due to its rapid onset of hypnosis and anticonvulsant properties, propofol is an alternative treatment for patients who are refractory to high-dose benzodiazepines. Advantages to its use are that it is easily titratable, with predictable effects, and has a rapid metabolic clearance.
Propofol is a phenolic compound unrelated to other types of anticonvulsants that has general anesthetic properties when administered IV. Growing numbers of anecdotal reports describe successful use of propofol in refractory status epilepticus. Intubation and ventilation are required. Hypotension may require treatment.
Beta2 Agonists
Class Summary
Bronchodilators may be used to relieve respiratory distress from organochlorine toxicity. Conceptually, however, beta-agonists could precipitate cardiac dysrhythmias in sensitized myocardium and hence should be used with caution in patients exposed to organochlorines.
Albuterol relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.
Anticholinergics, Respiratory
Class Summary
These agents are competitive inhibitors of acetylcholine and muscarine in the autonomic nervous systems and they relieve muscarinic effects, especially bronchorrhea. Inhaled anticholinergic agents (eg, ipratropium) may be considered. One caveat is that conceptually, anticholinergics can precipitate cardiac dysrhythmias in sensitized myocardium and should be used with caution in patients exposed to organochlorines.
Ipratropium is chemically related to atropine. It has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa.
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