Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) Black leaf
2) Nicotine liquid (synonym)
3) Nicotine gum (synonym)
4) Nicotine patch (synonym)
5) alpha-n-methyl-d-beta-pyridyl-pyrrolidine
6) 1-methyl-2-(3-pyridyl)pyrrolidine
7) 3-(n-methylpyrrolidino)pyridine
8) 3-(1-methyl-2-pyrrolidinyl)pyridine
9) (S)-3-(1-methyl-2-pyrrolidinyl)pyridine
10) L-3-(1-methyl-2-pyrrolidyl)pyridine
11) 3-(1-methyl-2-pyrrolidyl)pyridine
12) (-)-3-(1-methyl-2-pyrrolidyl)pyridine
13) (-)-Nicotine
14) l-Nicotine
15) L-Nicotine
16) (S)-Nicotine
17) Pyridine, 3-(1-methyl-2-pyrrolidinyl)-
18) beta-Pyridyl-alpha-N-methylpyrrolidine
19) beta-Pyridyl-O,N-methylpyrrolidine
20) Pyrrolidine, 1-methyl-2-(3-PYRIDAL)-
21) CAS 54-11-5
22) NICOTINE SULFATE, SOLID OR LIQUID

1.2.1) MOLECULAR FORMULA
1) C10-H14-N2
2) C20-H26-N4.O4-S

Available Forms Sources

A)

1) TOBACCO LEAVES

a) Tobacco leaves contain about 1% to 6% nicotine and when blended to make cigarettes or cigars, contain about 1% to 2% nicotine (4(6)).

2) SNUFF/CHEWING TOBACCO

a) SNUFF is prepared from powdered tobacco leaf and flavorings. Moist snuff contains from 4.6 to 32 mg of nicotine per gram of moist material, and 12.4 to 15.6 mg/g of dry snuff (Hoffmann et al, 1986). Most containers hold 30 g of snuff.
b) CHEWING TOBACCO (LEAF OR PLUG) contains about 2.5 mg nicotine per gram of dry material, although amounts as high as 8 mg/g have been reported (Gritz et al, 1981).

1) Betelquid and Pan Masala are popular chewing products that contain tobacco and other ingredients (Babu et al, 1996). It is used primarily in India, Pakistan, and some Asian countries.

3) CIGARETTES

a) CIGARETTE TOBACCO contains 13 to 30 mg nicotine per 1 whole cigarette; 1 low-yield cigarette contains 3 to 8 mg nicotine; 1 cigar contains 15 to 40 mg nicotine; 1 cigarette butt contains 5 to 7 mg nicotine (Salomon , 2002).

1) The actual nicotine "delivered" in smoke is 0.5 to 2.0 mg per 1 whole cigarette; 0.1 to 1.0 mg per 1 low-yield cigarette; 0.2 to 1.0 mg per cigar (Salomon , 2002).

b) IMPORTED CIGARETTES

1) BIDI are small, unfiltered, brown, hand-rolled cigarettes (they have the appearance of a marijuana cigarette) primarily produced in India and other southeast Asia countries, which consist of tobacco wrapped in a tendu or temburni leaf (Diospyros melanoxylon)((Anon, 1999)) and estimated to contain 3 times the amount of nicotine as regular cigarettes (BD Montgomery , 1999; Yen et al, 2000).

a) Bidis come in a wide variety of flavors (eg, vanilla, strawberry, chocolate, mandarin orange, mango, rootbeer) to mask the poor quality of the tobacco and are popular among teenagers for their taste, lower cost, and the potential ease of access over the internet (BD Montgomery , 1999; Yen et al, 2000).
b) Despite containing less tobacco, a single bidi produces 3 times as much nicotine and carbon monoxide as the standard American cigarette. Also, the tendu leaf wrapper does not burn well; therefore, a smoker has to inhale frequently and deeply, which could result in large amount of tar being deposited into the airways (Yen et al, 2000).
c) At the time of this review, there has been an attempt by US states to have bidi cigarettes outlawed; a formal letter to the Department of Health and Human Services has been signed by all 50 states (Yen et al, 2000).

2) KRETEK: A clove-flavored cigarette produced in Indonesia that may be referred to as "rokok kretek." . Traditionally, the cigarettes had cloves crushed and mixed in with tobacco. Today, fragrance and flavors chemicals are predominant, rather than crushed cloves in the cigarettes. Generally, they have higher nicotine levels than traditional cigarettes (Personal Communication, 2000).

4) NICOTINE LIQUID

a) Nicotine liquid is used with electronic-cigarettes. Refill cartridges contain liquid nicotine and are available in various strengths ranging from 6 mg/mL (0.6%) to 36 mg/mL (3.6%). It is estimated that 20 drops are equal to 1 mL of solution; 1 drop of 3.6% liquid contains 1.8 mg of nicotine. A potential ingestion of 1 to 2 drops of 3.6% solution (1.8 to 3.6 mg) could produce significant symptoms in a young child (Gupta et al, 2014). In addition, nickel contact allergy has been reported with the use of an electronic cigarette in an adult with a history of contact allergy; a dimethylglyoxime spot test was positive (Maridet et al, 2015).
b) HOOKAH/SECONDHAND EXPOSURE TO NICOTINE: In a study of the homes of hookah-only smokers and nonsmokers, the levels of indoor air nicotine (a marker of secondhand smoke), indoor surface nicotine (a measure of third-hand smoke), and a child's uptake of nicotine and other chemicals were measured to assess exposure in children living in the homes of hookah smokers. The findings showed significantly higher nicotine levels in indoor air and on surfaces in a child's bedroom in the homes of daily hookah smokers compared to the homes of nonsmokers. Uptake of nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and acrolein were significantly higher in children living in a home with a daily hookah smoker compared to children living in a nonsmoker home (Kassem et al, 2014).

5) NICOTINE GUM

a) Nicorette(R) contains 2 mg of nicotine in the form of a natural tobacco plant extract in an ion-exchange resin gum base. The gum is buffered to a pH of 8.5 to enhance buccal absorption.

6) NICOTINE TRANSDERMAL SYSTEMS

a) Habitrol(R) contains 17.5 mg, 35 mg, or 52.5 mg and releases 7 mg, 14 mg, and 21 mg daily, respectively.
b) Nicoderm(R) releases 7 mg, 14 mg, or 21 mg daily.
c) Prostep(R) contains 15 mg or 30 mg and releases 10 mg and 21 mg daily, respectively.
d) Nicotrol-16(R) contains 16.6 mg.

7) NICOTINE NASAL SPRAY

a) Nicotrol NS contains 10 mg/mL, and each actuation releases a metered 50 mL spray containing 0.5 mg nicotine. One spray in each nostril delivers a total of 1 mg nicotine (Prod Info Nicotrol NS(R), nicotine nasal spray, 1996).

8) AEROSOL RODS

a) Aerosol nicotine rods were evaluated as a substitute cigarette. Manufacturers of these rods are required to file a New Drug Application with the FDA (Slade & Connolly, 1987). Nicotine uptake by test subjects has been variable, limiting the aerosol rod's usefulness (deBethizy et al, 1988; Sepkovic et al, 1986).

9) Nicotine is available in the following forms: dihydrochloride, salicylate, sulfate, and bitartrate (Lewis, 1993).
10) POSSIBLE ROUTES OF EXPOSURE

a) Exposure to nicotine occurs during:

1) The mixing, storage, and application of insecticides.
2) The processing and extracting of tobacco.
3) Ingestion of cigarettes, snuff, or cigars.
4) Ingestion of nicotine liquid used in electronic-cigarettes (ie, refill cartridges containing nicotine liquid)
5) Administration of tobacco enemas to treat intestinal parasites.
6) Chewing of nicotine chewing gum used to aid in smoking cessation.
7) Contact with plants containing nicotine.
8) Usage or ingestion of nicotine-containing transdermal patches.

b) Little or no nicotine is now produced in the US, and limited supplies are imported from India (HSDB, 1997).

B)

1) Nicotine is used in medicines, as an insecticide and in tanning (ACGIH, 1991).
2) Nicotine is a highly toxic alkaloid that causes stimulation of the autonomic ganglia and the central nervous system. In its free state it is a pale yellow liquid that slowly darkens on exposure to air. Nicotine is derived from the stems and leaves of the tobacco plant and its primary usage is cigarettes.
3) Nicotine also is encountered in insecticide preparations as a crude 40% solution of the sulfate, which is applied as a spray or dust (Baselt & Cravey, 1995; Clayton & Clayton, 1994; Morgan, 1993). The pharmaceutical industry manufactures formulations containing nicotine (ITI, 1995). Nicotine has been used in the tanning process (NRC, 1989).
4) Nicotine is used in veterinary applications as an ectoparasiticide and anthelmintic (EPA, 1985).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) SOURCES: Found primarily in tobacco-containing products such as cigarettes, cigars, pipe tobacco, and chewing tobacco and also in nicotine replacement products such as gum, nasal sprays, patches, and electronic cigarettes. Also, found in the tobacco plant (Nicotiana tabacum) and some other plant species; occupational exposures may result from the harvesting or processing of tobacco plants (SEE Plants-Nicotinic Management). Nicotine may also be found in some insecticides (used in the developing world).
B) PHARMACOLOGY: Binds to nicotinic acetylcholine receptors that are found throughout the body, most notably in the autonomic nervous system (preganglionic sympathetic synapses and pre- and postganglionic parasympathetic synapses).
C) TOXICOLOGY: Toxic effects are dose-related and result from overstimulation of nicotinic receptors, often causing inhibition of receptor action following initial stimulatory effects.
D) EPIDEMIOLOGY: Very common exposure that can rarely result in significant morbidity and death, especially in children. May be an occupational exposure, commonly known as green tobacco sickness, from working with tobacco plants .
E) WITH THERAPEUTIC USE

1) ADVERSE EFFECTS: NICOTINE REPLACEMENT PRODUCTS: Symptoms may include local irritation from the gum, spray, or transdermal patch or systemic signs (eg, nausea and vomiting, sleep disturbances, headache, and chest pain) of nicotine toxicity. Absorption may occur after ingestion, inhalation, dermal, or rectal exposure.

F) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: GI upset, nausea, vomiting, dizziness, headache, tremor, diaphoresis, tachycardia, pallor, and hypertension are common events.
2) SEVERE TOXICITY: Seizures, confusion, weakness, bradycardia, hypotension, and respiratory muscle paralysis can develop.

0.2.3)

A) WITH POISONING/EXPOSURE

1) Hypertension, tachycardia, and tachypnea may occur, followed by hypotension, bradycardia, and bradypnea. Respiratory stimulation is one of the principal signs of nicotine poisoning. High doses can produce fatal respiratory depression of both central and peripheral origin.

0.2.20)

A) Nicotine is a possible human teratogen.
B) Nicotine is teratogenic in mice, but not in several other species. It crosses the placenta and is excreted in breast milk. It has reduced fertility in male and female rats.

0.2.21)

A) Use of smokeless tobacco has been shown to cause oral-pharyngeal cancer.

Laboratory Monitoring

A)

B)

C)

D)

E)

Treatment Overview

0.4.2)

A) MILD TO MODERATE TOXICITY

1) Treatment is primarily supportive and symptomatic. Vomiting is common, which tends to limit absorption. Intravenous fluids can be administered. Persistent vital sign abnormalities, altered mental status, muscle weakness, and seizures indicate a more severe poisoning.

B) SEVERE TOXICITY

1) Treatment is primarily symptomatic and supportive. Patients may need airway support and mechanical ventilation for altered mental status, respiratory distress, secretions or respiratory paralysis. Atropine can be given for bradycardia or significant muscarinic signs (ie, bronchorrhea), if present. Hypotension should be treated with intravenous fluids and then a vasopressor as needed. Benzodiazepines should be used to treat seizures or severe agitation. Death is primarily from respiratory failure.

C) DECONTAMINATION

1) PREHOSPITAL: Prehospital decontamination is unlikely to be of benefit as nicotine is rapidly absorbed and most patients with more than mild toxicity will have significant vomiting. Remove transdermal patches and wash skin.
2) HOSPITAL: Any transdermal patches should be removed from the skin and the area should be flushed with water, and wash exposed skin. Gastric decontamination is usually not necessary because patients often present with large amounts of vomiting. If the patient is not already vomiting, consider using activated charcoal and whole bowel irrigation following ingestion of a patch product in a child or ingestion of multiple patches by an adult.

D) AIRWAY MANAGEMENT

1) Patients with an altered mental status or respiratory muscle weakness may need mechanical respiratory support and orotracheal intubation.

E) ANTIDOTE

1) There is no specific antidote.

F) ENHANCED ELIMINATION

1) Enhanced elimination is rarely necessary as life threatening toxicity is rare. Multiple dose activated charcoal may be theoretically be beneficial in improving elimination by interrupting enterohepatic circulation, but it is rarely indicated and its use in this setting has not been described. Hemodialysis and hemoperfusion should be effective as nicotine has a small volume of distribution and low protein binding, but they are rarely if ever indicated and their use has not been described. The vast majority of patients do well with supportive care.

G) PATIENT DISPOSITION

1) HOME CRITERIA: Anyone with an intentional ingestion, symptoms other than vomiting, or children who have ingested more than 1 cigarette or 3 or more cigarette butts should be evaluated in a healthcare facility.
2) OBSERVATION CRITERIA: Patients who are asymptomatic after 4 to 6 hours following an oral ingestion of a non-patch product can be discharged. The appropriate duration of observation following ingestion of a patch by a child is not known, but these products contain enough nicotine to cause severe toxicity and may have very delayed absorption; therefore, prolonged observation (24 hours) is recommended in these cases.
3) ADMISSION CRITERIA: Patients with persistent vital sign abnormalities, seizures, altered mental status, or muscle weakness should be admitted.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following ingestion of nicotine replacement products by a child.

H) PITFALLS

1) Urine acidification (while theoretically helpful in enhancing elimination) is not recommended. Failure to adequately observe a patient who ingests a patch product. Avoid using a H2 blocker or proton pump inhibitor initially because nicotine will be absorbed more easily in an alkaline environment.

I) PHARMACOKINETICS

1) Volume of distribution is small at about 1 L/kg and protein binding is limited (about 5%). The half-life at therapeutic doses is about 1 to 2 hours. Peak concentrations are achieved within 0.5 to 2 hours with therapeutic doses. However, absorption may vary significantly by the nicotine delivery system: nasal spray (1 mg dose rises rapidly and can reach maximum venous concentrations of 2 to 12 ng/mL in 4 to 15 minutes) or nicotine inhaler (following a single inhalation the arterial nicotine rises slowly and does not reach the level of smoking a cigarette). Absorption of topical preparations can be significant, especially after repeated dosing.

J) TOXICOKINETICS

1) Symptoms typically develop within 30 minutes to 2 hours after an oral exposure. Symptoms may be immediate after inhalational exposure. Symptoms may be delayed after ingestion of patch products.

K) DIFFERENTIAL DIAGNOSIS

1) Poisoning by cholinergic agents such as organophosphates and carbamate pesticides may produce a similar presentation.

0.4.3)

A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

A)

B)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

1) ADVERSE EFFECTS: NICOTINE REPLACEMENT PRODUCTS: Symptoms may include local irritation from the gum, spray, or transdermal patch or systemic signs (eg, nausea and vomiting, sleep disturbances, headache, and chest pain) of nicotine toxicity. Absorption may occur after ingestion, inhalation, dermal, or rectal exposure.

F)

1) MILD TO MODERATE TOXICITY: GI upset, nausea, vomiting, dizziness, headache, tremor, diaphoresis, tachycardia, pallor, and hypertension are common events.
2) SEVERE TOXICITY: Seizures, confusion, weakness, bradycardia, hypotension, and respiratory muscle paralysis can develop.

Vital Signs

3.3.1)

A) WITH POISONING/EXPOSURE

1) Hypertension, tachycardia, and tachypnea may occur, followed by hypotension, bradycardia, and bradypnea. Respiratory stimulation is one of the principal signs of nicotine poisoning. High doses can produce fatal respiratory depression of both central and peripheral origin.

3.3.2)

A) WITH POISONING/EXPOSURE

1) Tachypnea may occur early, followed by bradypnea in severe poisonings.

3.3.3)

A) WITH POISONING/EXPOSURE

1) Diaphoresis may be observed with small doses.

3.3.4)

A) WITH POISONING/EXPOSURE

1) Hypertension may occur early, followed by hypotension in severe poisonings.

3.3.5)

A) WITH POISONING/EXPOSURE

1) Tachycardia may occur early, followed by bradycardia in severe poisonings.

Heent

3.4.3)

A) WITH POISONING/EXPOSURE

1) SUMMARY: Miosis, mydriasis, nystagmus, and lacrimation are common. Chronic use may cause tobacco-alcohol amblyopia.
2) Mydriasis may occur with large doses (Rosenweig et al, 1989; Haruda, 1989).
3) Lacrimation is common.
4) Nicotine sulfate is highly toxic and may burn the eyes.
5) Nicotine-induced nystagmus (NIN) is relatively common and can be produced after smoking a cigarette and also after chewing nicotine gum. It appears that nicotine induces an imbalance in the vestibulo-ocular reflex (Pereira et al, 2000).
6) Miosis has been reported with small doses (Rosenweig et al, 1989; Haruda, 1989).
7) Tobacco-alcohol amblyopia has been reported in chronic smokers who also have malnutrition and excessive alcohol consumption. It is characterized by progressive bilateral visual deterioration and loss of color vision (Kermode et al, 1989).

3.4.4)

A) WITH POISONING/EXPOSURE

1) Auditory disturbances may occur with nicotine poisoning (HSDB, 1997).

3.4.5)

A) WITH THERAPEUTIC USE

1) Inhalation can irritate the nose (EPA, 1985).

3.4.6)

A) WITH POISONING/EXPOSURE

1) SUMMARY: A burning sensation in the mouth or throat, headache, and salivation are common. Chronic effects of oral snuff use include leukoplakia and oropharyngeal cancer.
2) BURNING SENSATION: A burning sensation may occur in the mouth or throat.
3) Salivation may be profuse.
4) LEUKOPLAKIA: Long-term use of "smokeless" snuff orally has been shown to be habituating and result in gingival recession and a typical white and filmy lesion without elevation from the surrounding oral mucosa (Belonger & Paulson, 1983).

a) Leukoplakia is considered a premalignant lesion (Moore et al, 1986).

5) ORAL SUBMUCOUS FIBROSIS: It has been described as a chronic disease of the oral mucosa, which is characterized by inflammation and progressive fibrosis of the lamina propria and deeper connective tissue in individuals who habitually chew panmasala and betel liquid (Babu et al, 1996). These products contain tobacco and are popular in India, Pakistan, and some Asian countries.
6) Oropharyngeal cancer has been reported after chronic use of "smokeless" tobacco.

Cardiovascular

3.5.2)

A) TACHYARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) Acute cardiovascular effects of nicotine can include the following: increased heart rate (up to 10 to 15 beats per minute [bpm]), increased blood pressure (up to 5 to 10 mmHg) and increased cardiac output (secondary to increased heart rate and myocardial contractility), and nicotine-mediated catecholamine release resulting in constriction of coronary arteries (Benowitz & Gourlay, 1997).
b) CASE REPORT: A 35-year-old patient developed agitation, hypertension, tachycardia, dizziness, and nausea after ingesting 7 to 20 cigarettes. Following supportive care, he recovered and was transferred within 24 hours for further psychiatric care (Metzler et al, 2005).

B) HYPERTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) In small amounts, nicotine may cause increased blood pressure; frequently transient.
b) CASE REPORT: Elevated blood pressure was reported in a 69-year-old woman following a suicide attempt with application of 2 nicotine patches left on her body for 2 weeks. Her blood pressure returned to normal 4 hours after removal of the patches and skin cleansing (Woolf et al, 1996).

C) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) In large doses, decreased blood pressure and pulse may be noted followed by cardiac arrhythmias.
b) CASE REPORT: Refractory shock, after successful CPR, was reported in a 32-year-old man following the use of multiple patches (plasma nicotine concentration 11 hours after arrest was 3.7 mcg/mL) without apparent decrease in tobacco consumption. He died 4 days later (Sanchez et al, 1996).
c) CASE REPORT: An 11-year-old boy developed nausea and vomiting, severe weakness, palpitation, headache, and abdominal pain after applying 2 nicotine patches on his arm a few hours apart. Although his vital signs were normal on presentation, his blood pressure dropped to 90/60 mmHg, and pulse dropped to 70 bpm during his stay. Intramuscular atropine sulfate (0.02 mg/kg body weight) was administered; he became asymptomatic after 4 hours (Wain & Martin, 2004).

D) CONDUCTION DISORDER OF THE HEART

1) WITH POISONING/EXPOSURE

a) CASE REPORTS

1) SINOAURICULAR BLOCK: An 18-month-old child demonstrated sinoauricular block following the ingestion of one-fifth of a regular cigarette (approximately 4 mg nicotine) (Gyllensward & Nordbring, 1953).
2) QT PROLONGATION: Prolonged QT complex was reported in a 37-year-old man following a suicide attempt with application of 12 nicotine patches simultaneously (Woolf et al, 1996).

E) ATRIAL FIBRILLATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Atrial fibrillation has been reported in a 52-year-old man with preexisting heart disease who ingested 6 pieces of nicotine gum in 1 day (Rigotti & Eagle, 1986).
b) CASE REPORT: Atrial fibrillation in a 35-year-old man with no history of heart disease was associated with chewing 30 pieces of 2 mg nicotine gum daily (Stewart & Catterall, 1985).

F) MYOCARDIAL INFARCTION

1) WITH THERAPEUTIC USE

a) LIQUID NICOTINE: A 24-year-old man was admitted with chest pain of 4 hours duration while using liquid nicotine. He had a 1-month history of using liquid tobacco containing 16 mg of nicotine daily (approximately equivalent to 1 pack of cigarettes) and prior to that he had a 4-year history of smoking one pack of cigarettes daily. An ECG showed ST segment elevation on leads DI, aVL and V1-6 with reciprocal ST segment depression and T-wave inversion on leads a VF, DII and DIII. An echocardiogram was consistent with anterior wall hypokinesis with an ejection fraction of 50%. A troponin level was 223 pg/mL (normal range: 0 to 14 pg/mL). A thrombus in the proximal left anterior descending artery was found on cardiac catheterization. Due to his age and no underlying health conditions, the patient was treated with tissue plasminogen activator which relieved his chest pain and the ECG showed a 70% resolution of ST elevation (Kivrak et al, 2014).

G) VENTRICULAR FIBRILLATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 17-year-old ingested nicotine and developed ventricular fibrillation within 2 minutes. He converted to sinus tachycardia with premature ventricular contractions (PVCs) after epinephrine and defibrillation. The patient died of intractable hypertension and anoxic brain death (Lavoie & Harris, 1991).

H) CARDIAC ARREST

1) WITH POISONING/EXPOSURE

a) CASE REPORT/COMBINATION EXPOSURE: A 32-year-old man was found in cardiac arrest following an episode of dizziness. Following CPR, cardiac activity was recovered, but he remained in nonreactive coma 11 hours later. No ECG signs of cardiac ischemia or dysrhythmias were apparent. He died 4 days later. The family reported the victim's use of multiple nicotine patches with no decrease in tobacco use (Sanchez et al, 1996).
b) CASE REPORT/LIQUID NICOTINE: A 24-year-old woman was found in pulseless electrical activity and had a return of spontaneous circulation after 10 minutes of CPR only (no medications administered) following the intentional ingestion (time of ingestion unknown) of liquid nicotine and whiskey. Two empty 15 mL vials of concentrated nicotine (100 mg/mL) were found near the patient and a suicide note. She was intubated in the field and arrived in the ED about 10 minutes later with fixed and dilated pupils, incontinence, hypotension (74/53 mmHg) and a pulse rate of 106 beats/min. The endotracheal tube required adjustment due to right mainstem intubation. The patient responded slightly to painful stimuli only. A comprehensive drug screen was positive for only nicotine, cotinine, and her previously prescribed medications (ie, trazodone, fluoxetine, and olanzapine). Her nicotine level obtained shortly after arrival was greater than 1000 ng/mL (measured by LC/MS/MS). She continued to have myoclonic jerking despite drug therapy and was noted to have an absent corneal, gag or cough reflexes. An EEG was consistent with poor cerebral dysfunction. On day 2, a MRI of the brain showed multiple acute infarcts consistent with anoxic brain injury. Due to her poor prognosis, intensive treatment was stopped and the patient died 3 days after ingestion (Chen et al, 2015).
c) CASE REPORT/LIQUID NICOTINE: Ingestion of an unknown amount of 40% solution of nicotine sulfate (357 mg of nicotine/mL) resulted in a cardiac arrest in a 15-year-old. An ECG revealed sinus tachycardia (rate 144 bpm) with multiple atrial premature contractions. After resuscitation, the patient was hypotonic with decerebrate posturing with midline, fixed pupils with the right slightly larger than the left. The patient never recovered cognitive function (Rogers et al, 2004).

I) VASOSPASM

1) WITH POISONING/EXPOSURE

a) Vasoconstriction occurred in volunteers biting the transdermal nicotine patch Prostep(R), with subsequent oral absorption (Harchelroad et al, 1992).

J) CHEST PAIN

1) WITH THERAPEUTIC USE

a) TRANSDERMAL NICOTINE PATCH: Chest pain has been reported following the therapeutic use of patches (Henningfield, 1995).

Respiratory

3.6.2)

A) HYPERVENTILATION

1) WITH POISONING/EXPOSURE

a) Tachypnea is common initially.

B) DYSPNEA

1) WITH POISONING/EXPOSURE

a) Dyspnea occurs after tachypnea.

C) IRRITATION SYMPTOM

1) WITH POISONING/EXPOSURE

a) Airway irritation in the lower neck and upper chest region with associated cough has been shown to be directly correlated to nicotine content in cigarette smoke. Hexamethonium, a nicotinic blocking agent, blocks the respiratory tract irritation when administered prior to cigarette smoke inhalation (Lee et al, 1993).

D) APNEA

1) WITH POISONING/EXPOSURE

a) Respiratory failure may occur rapidly (5 minutes postingestion), especially with large ingestions, and may be fatal (Singer & Janz, 1990).

E) PULMONARY ASPIRATION

1) WITH POISONING/EXPOSURE

a) Aspiration pneumonitis developed in a 32-year-old man who sustained a cardiac arrest after suspected nicotine overdose (Sanchez et al, 1996).

F) SPUTUM ABNORMAL - AMOUNT

1) WITH POISONING/EXPOSURE

a) Increased secretions are a common cholinergic effect.

Neurologic

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) Confusion, anxiety, dizziness, restlessness, and incoordination may occur.
b) CASE REPORT: Lethargy and depressed respirations were reported in an 8-month-old infant 2.5 hours after ingesting 2 cigarette butts. Lethargy progressed to obtundation with minimal responsiveness. Gradual improvement occurred, with recovery by the third day (Borys et al, 1988).
c) Stupor, confusion, and dizziness were reported in 2 patients following suicide attempts with nicotine dermal patches. No coingestants were involved (Woolf et al, 1996).
d) CASE REPORT: A 67-year-old man, with a history of cerebral infarct of the right hemisphere, intentionally ingested a nicotine extract (prepared by extracting 300 g of tobacco, producing an estimated 6780 mg of nicotine). The "recipe" was found on an Internet site. The patient drank the extract and immediately felt ill and vomited. Upon admission, the patient was somnolent and showed marked hyperextension of the neck and slurred speech. Tachycardia was observed, which normalized on the second day. The patient gradually improved with supportive care and returned to baseline within 4 days (Schneider et al, 2009). The authors suggested that only a portion of the extract was absorbed due to vomiting, and residue of the extract was also found near the patient.
e) CASE REPORT: A 35-year-old man developed agitation, hypertension, tachycardia, dizziness, and nausea after ingesting 7 to 20 cigarettes. Following supportive care, he recovered and was transferred to psychiatric care within 24 hours of admission (Metzler et al, 2005).

B) HEADACHE

1) WITH THERAPEUTIC USE

a) TRANSDERMAL NICOTINE PATCH: Headache has been reported following the therapeutic use of patches (Henningfield, 1995).

2) WITH POISONING/EXPOSURE

a) Headache may occur after oral or dermal exposure to small amounts of nicotine (Haruda, 1989).

C) PSYCHOMOTOR AGITATION

1) WITH POISONING/EXPOSURE

a) Agitation is common in young children with tobacco ingestion (Smolinske et al, 1988).

D) TREMOR

1) WITH POISONING/EXPOSURE

a) Even 2 cigarettes (nicotine) increased the amplitude but not the frequency of hand tremors associated with habitual smokers (Shiffman et al, 1983).

E) HYPOREFLEXIA

1) WITH POISONING/EXPOSURE

a) NEUROMUSCULAR DEPRESSION: Following a large ingestion, weakness, fasciculations, hypotonia, and decreased deep tendon reflexes, progressing to paralysis may occur.

F) SEIZURE

1) WITH POISONING/EXPOSURE

a) In large doses, nicotine may cause seizures.
b) CASE REPORTS

1) ANORECTAL EXPOSURE: A toddler had a generalized grand mal seizure 15 minutes following the administration of a tobacco infusion enema (Oberst & McIntyre, 1953).
2) CIGARETTES: Seizures were reported in 4 children who ingested 2 cigarettes each (Malizia et al, 1983).
3) GUM: Seizures and apnea were attributed to nicotine gum ingestion in a 20-month-old child (Singer & Janz, 1990); however, the ingestion was not confirmed.
4) TRANSDERMAL PATCH: Seizure was reported in an 11-month-old after a used nicotine patch (21 mg/24 hr) inadvertently adhered to the infant's skin (Ryan et al, 1999). Symptoms of lethargy continued until the patch was found and removed, with a marked improvement noted at 15 minutes and complete resolution within 4 hours.

Gastrointestinal

3.8.2)

A) GASTROINTESTINAL IRRITATION

1) WITH POISONING/EXPOSURE

a) A burning sensation is the initial symptom. It is present in the mouth, throat, esophagus, and stomach.

B) EXCESSIVE SALIVATION

1) WITH POISONING/EXPOSURE

a) Salivation occurs after small doses.

C) NAUSEA AND VOMITING

1) WITH THERAPEUTIC USE

a) TRANSDERMAL NICOTINE PATCH: Nausea and vomiting have been reported following the therapeutic use of patches (Henningfield, 1995).

2) WITH POISONING/EXPOSURE

a) Vomiting may occur very early (within minutes) after tobacco ingestion, minimizing absorption and other toxic manifestations (Lavoie & Harris, 1991). Vomiting occurs in 16% to 63% of tobacco and nicotine chewing gum ingestions in children (Smolinske et al, 1988; Bonadio & Anderson, 1989) (Edwards & Volan, 1985) (Peder et al, 1984) (Litleskare et al, 1994).
b) CASE REPORT: A 35-year-old man developed agitation, hypertension, tachycardia, dizziness, and nausea after ingesting 7 to 20 cigarettes. Following supportive care, he recovered and was transferred to the psychiatry department within 24 hours of hospitalization (Metzler et al, 2005).

D) ABDOMINAL PAIN

1) WITH POISONING/EXPOSURE

a) Abdominal pain occurs with low doses and is usually not severe.

E) DIARRHEA

1) WITH POISONING/EXPOSURE

a) Diarrhea has been reported with low doses. A delayed (4 to 24 hours) symptom occurs in 14% of pediatric tobacco ingestions (Smolinske et al, 1988).
b) CASE REPORT: Voluminous diarrhea, estimated at 1 L/hr, developed in a 32-year-old man who sustained a cardiac arrest after suspected nicotine overdose (Sanchez et al, 1996).

F) GASTRITIS

1) WITH POISONING/EXPOSURE

a) "GREEN TOBACCO SICKNESS": A mild form of nicotine poisoning has been reported in both adults and children, smokers and nonsmokers, working on tobacco farms. The usual presentation is an individual who has been handling wet, uncured tobacco leaves for 6 hours or more per day , with the onset of signs and symptoms 3 to 24 hours later (Gehlbach et al, 1975; Ross et al, 1994a; Ross et al, 1994b; McKnight et al, 1994; Hipke, 1993). Symptoms can include nausea and vomiting and can be treated with antiemetics. Prevention can be accomplished by using protective clothing.

Genitourinary

3.10.2)

A) ACUTE RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Acute renal failure attributed to rhabdomyolysis (myoglobin 18700 mcg/L, CPK 7007 IU/L) developed in a 32-year-old man who sustained a cardiac arrest following suspected nicotine overdose (plasma nicotine concentration 11 hours after arrest was 3.7 mcg/mL) (Sanchez et al, 1996).

Dermatologic

3.14.2)

A) EXCESSIVE SWEATING

1) WITH POISONING/EXPOSURE

a) Intense sweating may occur.
b) CASE REPORT: A 37-year-old man was reported to have pallor and sweating 2 hours after application of 12 nicotine patches (Woolf et al, 1996).

B) DERMATITIS

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL DERMATOSES: Nicotine and its derivatives have shown positive reactions in human skin patch tests and dermatoses have been reported by workers processing tobacco or working in nicotine production (Clayton & Clayton, 1994).

C) ERUPTION

1) WITH THERAPEUTIC USE

a) TRANSDERMAL NICOTINE PATCH: Skin rash has been reported following the therapeutic use of patches (Henningfield, 1995).

Musculoskeletal

3.15.2)

A) RHABDOMYOLYSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Probable rhabdomyolysis (myoglobin 18700 mcg/L, creatine kinase 7007 IU/L) was reported in a 32-year-old man who sustained cardiac arrest after suspected nicotine overdose (Sanchez et al, 1996).

Immunologic

3.19.2)

A) ACUTE ALLERGIC REACTION

1) WITH THERAPEUTIC USE

a) TRANSDERMAL NICOTINE PATCH: Allergic skin reactions have been reported following the therapeutic use of patches (Henningfield, 1995).

Reproductive

3.20.1)

A) Nicotine is a possible human teratogen.
B) Nicotine is teratogenic in mice, but not in several other species. It crosses the placenta and is excreted in breast milk. It has reduced fertility in male and female rats.

3.20.2)

A) EMBRYOTOXICITY

1) Developmental abnormalities in the cardiovascular system were observed in the offspring of a woman who ingested nicotine. Toxic effects on the embryo have also been observed in the monkey (RTECS, 1997).

B) ERYTHROCYTES ABNORMAL

1) Although smoking may not cause significant changes in maternal hemoglobin, fetal blood shows changes consistent with chronic carbon monoxide poisoning, ie, a left shift in the O2 saturation of hemoglobin, and an increase in hematocrit and total hemoglobin (Bureau et al, 1983). Buchan (1983) measured blood viscosity in newborns of mothers who smoked more than 20 cigarettes per day. He found a 30% increase composed of a 12% increase in packed cell volume and an 18% decrease in red cell deformability.

C) ANIMAL STUDIES

1) EMBRYOTOXICITY

a) Nicotine was teratogenic in the mouse, but not in the rat, cow, sheep, or rabbit (Schardein, 1993). Nicotine produced skeletal system malformations in mice when injected subcutaneously on days 9 to 11 of gestation (Nishiura & Nakai, 1958).
b) Nicotine sulfate produced defects in the cervical cord and neural tube of chicks when injected into the vitellin sac at 48 hours. At 72 hours it produced abnormal cervical vertebrae (Landauer, 1960). When given on day 5, it produced smaller chicks (HSDB, 1997). The significance of this finding for human exposure is unknown.

2) FETOTOXICITY

a) In rodent studies, fetotoxicity, biochemical, metabolic, behavioral effects, and specific developmental abnormalities of skin appendages, the craniofacial area, the urogenital system, the respiratory system, and the musculoskeletal system were observed. Fetal death and changes in growth statistics and the weaning or lactation index were also observed (RTECS, 1997).
b) Fetal rats had reduced brain development and body weight after subcutaneous injection of 6 mg/kg/day from days 4 to 20 of gestation (Slotkin et al, 1986). Fetal rats exposed in utero to infused nicotine had impairment of cardiac function during postnatal hypoxia (Slotkin et al, 1997).

3) BONE DEVELOPMENT ABNORMAL

a) Delayed ossification and reduced fetal weight were produced in rats given aqueous extracts of smokeless tobacco equivalent to 6 mg/kg nicotine on days 6 to 18 of gestation (Paulson et al, 1994).

4) EMPHYSEMA

a) Emphysema-like damage involving defects in elastic tissue formation occurred in the lungs of fetal rats with dams exposed to 1 mg/kg nicotine per day on day 7 of gestation to birth (Maritz et al, 1993). Exposure was continued by nursing until 3 weeks after birth.

5) PERSONALITY DISORDER

a) Prenatal nicotine exposure in rodents is associated with postnatal behavioral abnormalities or neurotransmitter changes in a number of studies using various methodologies (Cutler et al, 1996) Seidler at al, 1994; (Paulson et al, 1994; van de Kamp & Collins, 1994).

6) DEATH

a) Increased postnatal deaths and some behavioral differences were seen in rats treated with smokeless tobacco extracts on days 6 to 20 of gestation at doses up to 18 mg/kg of nicotine per day (Paulson et al, 1994).

3.20.3)

A) HYPOXIA

1) Although smoking may not cause significant changes in maternal hemoglobin, fetal blood shows changes consistent with chronic carbon monoxide poisoning, ie, a left shift in the O2 saturation of hemoglobin, and an increase in hematocrit and total hemoglobin (Bureau et al, 1983).

B) BIRTHWEIGHT

1) ENVIRONMENTAL TOBACCO SMOKE

a) Eskenazi et al (1995), in a controlled study, reported an inverse relationship between maternal serum cotinine levels and birthweight. Every nanogram per milliliter increase in maternal cotinine level decreased birthweight by 1 gram.

C) PLACENTAL BARRIER

1) Nicotine freely passes into the placenta and is found in both amniotic fluid and umbilical cord blood (Luck & Nau, 1984; Hibberd et al, 1978).
2) In a short-term study of transderm nicotine replacement (total time patch worn = 480 minutes), no adverse maternal or fetal effects were reported (Wright et al, 1997).
3) Nicotine use during the last trimester has been associated with a decrease in fetal breathing movements, possibly resulting from decreased placental perfusion (Prod Info Nicorette(R), Nicotine polacrilex, 1991). Nicotine is readily transferred to the fetus throughout pregnancy; the fetus is actually exposed to higher nicotine concentrations than the mother (Luck et al, 1985).

D) ERYTHROCYTES ABNORMAL

1) Buchan (1983) measured blood viscosity in newborns of mothers who smoked more than 20 cigarettes per day. He found a 30% increase composed of a 12% increase in packed cell volume and an 18% decrease in red cell deformability.

E) DIABETES

1) In a study of 4917 patients from the British National Child Development Study observed through age 33 years, maternal smoking during pregnancy was associated with an increased risk of type 2 diabetes in the offspring(Montgomery & Ekbom, 2002). Odds ratio of developing type 2 diabetes between ages 16 and 33 years for offspring of women who were medium to heavy smokers (self-reported smoking varied between 1 and 9 cigarettes/day and more than 10/day) was 4.13 (95% CI, 1.27 to 13.4). The odds ratio for developing type 2 diabetes between ages 16 and age 33 years in offspring of heavy smokers (more than 10 cigarettes/day) was 4.55 (95% CI, 1.82 to 11.36).

F) PRETERM DELIVERY AND PREECLAMPSIA

1) In one study, 789 snuff (smokeless tobacco) users and 11,240 smokers were compared with 11,495 nonusers to evaluate the effects of tobacco use during pregnancy. Snuff use during pregnancy was associated with restricted fetal growth (adjusted mean birth weight reduced in snuff users by 39 g compared with nonusers; 95% CI, 6 to 72 g) and increased preterm delivery risk (adjusted odds ratio, 1.98; 95% CI, 1.46 to 2.68). Cigarette smoking during pregnancy was associated with restricted fetal growth (adjusted mean birth weight reduced in smokers by 190 g compared with nonusers; 95% CI, 178 to 202 g), and increased preterm delivery risk (adjusted odds ratio, 1.57; 95% CI, 1.38 to 1.80). Although preeclampsia was reduced in smokers (adjusted odds ratio, 0.63; 95% CI, 0.53 to 0.75), snuff use was associated with increased risk of preeclampsia (adjusted odds ratio, 1.58; 95% CI, 1.09 to 2.27) (England et al, 2003).

G) ANIMAL STUDIES

1) In rodent studies, toxic effects were observed in parturition and in the postpartum stage. Changes in litter size, viability index, live birth index, postimplantation mortality and stillbirth were also observed (RTECS, 1997).

3.20.4)

A) PERINATAL DISORDER

1) Nicotine is excreted in breast milk in small quantities that are not usually clinically important (Ferguson et al, 1976). However, heavy smoking by the mother may cause nausea or vomiting in the nursing infant, as well as behavioral changes (Abel, 1984).

B) BREAST MILK

1) The milk:serum nicotine concentration ratio averaged 2.92 in 1 group of nursing smokers (Luck & Nau, 1984a) and the nursing infants' serum:maternal serum nicotine concentration was 0.06 (Luck & Nau, 1984).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS54-11-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

A) Use of smokeless tobacco has been shown to cause oral-pharyngeal cancer.

3.21.3)

A) CARCINOMA

1) ORAL-PHARYNGEAL CANCER: The use of smokeless tobacco has been shown to cause oral-pharyngeal cancer, primarily of the cheek and gums. Snuff dippers have a 4.2 times greater risk for oral cancer and a 50 times greater risk of buccal mucosa cancer than nonsmoking, nonchewing patients (Winn et al, 1981).
2) Leukoplakia (white mucosal lesions) is found in 18% to 64% of users. Between 1.8% and 17.5% of leukoplakias eventually become malignant (Connolly et al, 1986).
3) Moist snuff (US brands) contain various carcinogens, including aromatic hydrocarbons, radiation-emitting polonium, and various nitrosamines in concentrations of 9600 to 289,000 parts per billion (Palladino et al, 1986; MMWR, 1985; Tricker et al, 1988). Newer brands have reduced the amount of nitrosamines (Hoffmann et al, 1991).

3.21.4)

A) CARCINOMA

1) Nicotine has not been carcinogenic in rats with chronic feeding or subcutaneous injection (Clayton & Clayton, 1994). Anecdotal observation has revealed a correlation between appearance of esophageal tumors in sheep and the use of nicotine-containing dips (Schuette, 1968).

B) IN VITRO

1) A study with the use of culture systems and animal xenograft models showed that nicotine stimulates the progression of tumor growth through a cyclooxygenase-2-dependent pathway. The authors noted that based on these findings, nicotine seems to be a potent mitogenic agent in modulating tumor cell proliferation. The authors noted that selective cyclooxygenase-2 inhibiting agents are promising antitumor agents for nicotine-associated gastric cancer (Shin & Cho, 2005).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) No testing is required in patients with mild or no symptoms.
B) Serum chemistries, creatine kinase, lactate, urinalysis should be performed in patients with severe poisonings.
C) Obtain an ECG and institute continuous cardiac monitoring in all symptomatic patients.
D) Serum levels are not readily available or useful to guide management.
E) Urine cotinine levels can be obtained for occupational monitoring.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) Nicotine laboratory determination is normally not performed.
2) Monitor serum electrolytes, kidney function tests, and CPK in severely symptomatic patients.
3) The concentration of nicotine in the plasma of nonsmokers has ranged from 0 to 0.006 mg/L. Smokers have ranged from 0.012 to 0.044 mg/L 30 minutes after a 6.5-hour period of smoking (Baselt & Cravey, 1995).
4) The steady-state level in plasma of persons chewing nicotine gum containing 2 mg or 4 mg is 0.012 or 0.023 mg/L, respectively (Baselt & Cravey, 1995).
5) Postmortem blood levels have ranged from 11 to 63 mg/L in persons who ingested 10 to 25 g nicotine sulfate (Baselt & Cravey, 1995).

4.1.3)

A) URINARY LEVELS

1) SUMMARY: In general, smokers will have urine cotinine levels greater than 50 nanograms(ng)/mL. Even environmental exposure to smoke will produce a urine value of less than 20 ng/mL in 92% of tested cases. Consumption of nicotine-containing foods in regular amounts are also likely to elevate urine cotinine above 50 ng/mL (Apseloff et al, 1994).
2) Cotinine levels in plasma, saliva, and urine correlate with passive exposure to smoke.
3) Urine cotinine levels can be used to follow occupational exposure in tobacco pickers (4(6)).

B) URINALYSIS

1) Monitor urinalysis and urine myoglobin in severely symptomatic patients.

4.1.4)

A) OTHER

1) MONITORING

a) Monitor ECG and vital signs in symptomatic patients.

2) SALIVA

a) Levels of COTININE in saliva have been a somewhat useful measure of recent cigarette consumption, but greater accuracy is obtained by correcting for age and a cubic nonlinear component (Swan et al, 1993).
b) Salivary cotinine measurements may be utilized to determine smoking status in the presence of a transdermal patch or other nonoral source of nicotine (WHO, 1994).

3) HAIR

a) SUMMARY: Neonates whose mothers were exposed to passive (environmental) smoke, as well as those of maternal smokers, have significantly higher concentrations of hair cotinine when compared with those whose mothers have had no smoke exposure (Koren, 1995).

1) Levels of cotinine, nicotine, or both in fetal hair are useful for documenting smoking during pregnancy. Methods have been published for determining levels of nicotine and cotinine in fetal and maternal hair (Klein et al, 1994; Kintz & Mangin, 1993).
2) A radioimmunoassay method has a lower limit of sensitivity of 0.25 ng/mg hair for nicotine and 0.1 ng/mg hair for cotinine, based on a 2 mg sample of hair (Klein et al, 1994).

Methods

A)

1) High pressure liquid chromatography methodology is available (Kyerematen et al, 1982)
2) A method for analysis of nicotine in fetal and maternal hair samples involves decontamination in methylene chloride, homogenization in sodium hydroxide, extraction in diethyl ether at pH 14, separation on a BP-5 capillary column, and quantification using gas chromatography/mass spectrometry (Kintz & Mangin, 1993).

B)

1) Aalders et al (1986) describe a method of analysis that can be used for nicotine, cotinine, or both in urine or plasma.
2) Nicotine laboratory determination is normally not performed.

Treatment

Oral Exposure

6.5.1)

A) SUMMARY

1) Onset of symptoms may be rapid (Malizia et al, 1983). Emesis is usually spontaneous. Since seizures or lethargy may occur within 15 minutes, IPECAC-INDUCED EMESIS OR ACTIVATED CHARCOAL IS NOT ADVISED IN THE PREHOSPITAL SETTING. Remove transdermal patches and wash exposed skin.

6.5.2)

A) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

3) Multiple dose activated charcoal may enhance the elimination of nicotine, although there are no data to confirm this hypothesis and its use is not routinely recommended (Ivey & Triggs, 1978) (4(6)).

6.5.3)

A) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

B) ATROPINE

1) Atropine may be used for control of signs of excess parasympathetic stimulation.
2) ATROPINE/DOSE

a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.

1) There is no minimum dose (de Caen et al, 2015).
2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).

C) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

D) MONITORING OF PATIENT

1) No testing is required in patients with mild or no symptoms.
2) Serum chemistries, creatine kinase, lactate, urinalysis should be performed in a patient with severe poisoning.
3) Obtain ECG in symptomatic patients, monitor cardiac function closely.
4) Serum levels are not readily available or useful to guide management. Urine levels can be obtained for occupational monitoring.

E) ANTACID

1) Antacids are contraindicated because nicotine is better absorbed in an alkaline media (Ivey & Trigg, 1978).

F) RHABDOMYOLYSIS

1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) SUPPORT

1) Emesis may be dangerous due to rapid onset of symptoms. Symptomatic care for hypotension or hypertension and for seizures should be given.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

6.8.2)

A) SUPPORT

1) Emesis may be dangerous, due to rapid onset of symptoms. Symptomatic care for hypotension or hypertension and for seizures should be given.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Use cool water when washing; hot water may speed absorption of nicotinic substances still present on the skin (Hipke, 1993).

6.9.2)

A) SUPPORT

1) Symptomatic care for hypotension or hypertension and for seizures should be given.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

A)

1) Enhanced elimination is rarely necessary as life threatening toxicity is rare. Multiple dose activated charcoal may be theoretically beneficial in improving elimination by interrupting enterohepatic circulation, but it is rarely indicated and its use in this setting has not been described. Hemodialysis and hemoperfusion should be effective as nicotine has a small volume of distribution and low protein binding, but they are rarely if ever indicated and their use has not been described. The vast majority of patients do well with supportive care.

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with persistent vital sign abnormalities, seizures, altered mental status, or muscle weakness should be admitted.

6.3.1.2) HOME CRITERIA/ORAL

A) SUMMARY: Anyone with an intentional ingestion, symptoms other than vomiting, or children who have ingested more than 1 cigarette or 3 or more cigarette butts should be evaluated in a health care facility.
B) CASE SERIES: In a prospective series of 347 children (mean age 14 months) who ingested nicotine-containing products (137 cigarettes, 187 cigarette butts, 3 cigars, 2 loose tobacco, 15 pieces of nicotine gum, and 1 nicotine patch), only 8 children were evaluated at a health care facility, and all were discharged without problems. Vomiting developed in 104 children (30%), mild CNS symptoms such as restlessness developed in 28 (8%), and 227 (65%) remained asymptomatic. The quantity of the tobacco ingested was not reported. The authors concluded that most children who ingest tobacco products can be safely managed at home (Johnson & Wilkins, 1996). In another prospective study of 700 children, significant toxicity (ie, seizures) was not reported. Children that were initially asymptomatic did not subsequently develop symptoms. The lack of early symptoms (ie, onset of vomiting within 20 minutes or less {observed in 97.9% of symptomatic children}) appeared to be a likely predictor of no subsequent toxicity. Due to the difficulty in quantifying the exact amount a child has ingested, the type and onset of symptoms appears to be a better predictor of outcome (McGee et al, 1995).
C) PEDIATRIC INGESTION: In another study of pediatric cigarette ingestion, assuming a cigarette contains a minimum of 13 mg of nicotine, severe toxicity was reported in 3 children ingesting 1.4 to 1.9 mg/kg of nicotine; children ingesting a mean of 0.8 mg/kg (range: 0.2 to 1.8 mg/kg) developed mild symptoms and children ingesting a mean of 0.5 mg/kg (range: 0.3 to 1 mg/kg) remained asymptomatic (Smolinske et al, 1988).

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following ingestion of nicotine replacement products by a child.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients who are asymptomatic after 4 to 6 hours following an oral ingestion of a non-patch product can be discharged. The appropriate duration of observation following ingestion of a patch by a child is not known, but these products contain enough nicotine to cause severe toxicity and may have very delayed absorption, therefore, prolonged observation (24 hours) is recommended in these cases.

6.3.5)

6.3.5.5) OBSERVATION CRITERIA/DERMAL

A) TRANSDERMAL PATCHES/ADULT: Woolf et al (1996) observed 55 adults who had misused or overdosed on dermal application of transdermal patches (2 to 20 patches). Those who had deliberately placed multiple patches on themselves (n=9) were also likely to have ingested other substances in suicide attempts. This presentation is usually clinically serious, including CNS, cardiovascular, and respiratory complications. Most patients exposed to multiple patches required hospital admission (Woolf et al, 1996).

Monitoring

A)

B)

C)

D)

E)

Abstracts

Case Reports

A)

1) ORAL

a) NICOTINE GUM: A case of nicotine overdose was reported in a 23-year-old woman following chewing of a single 2 mg piece of Nicorette(R) gum. The patient was a 2 pack/day smoker. On routine examination the day prior to beginning Nicorette(R), her blood pressure was 100/70 mmHg. Following chewing 1 piece of gum for approximately 60 seconds, the patient felt nauseated and tremulous. Within 20 minutes she became nauseated, flushed, had a dry mouth, and experienced palpitations. She began to sweat profusely and noted pruritus (Mensch & Holden, 1984).

1) She was transported to the emergency room and on the way experienced blurred vision and mental confusion. Initial examination in the ER revealed a blood pressure of 86/50 and pulse of 120/minute. She recovered uneventfully following Compazine(R), morphine, and atropine. It was unclear why this patient experienced toxic symptoms after chewing a single 2 mg piece of Nicorette(R).

b) NICOTINE GUM: Atrial fibrillation has been reported in a 52-year-old man with preexisting heart disease who ingested 6 pieces of nicotine gum in 1 day (Rigotti & Eagle, 1986).
c) NICOTINE GUM: Atrial fibrillation in a 35-year-old man with no history of heart disease was associated with chewing 30 pieces of 2 mg nicotine gum daily (Stewart & Catterall, 1985).
d) NICOTINE: A 17-year-old ingested nicotine and arrested within 2 minutes. Epinephrine was used to convert to ventricular fibrillation, the defibrillation was used to produce sinus tachycardia with PVCs. The patient died of intractable hypertension and anoxic brain death (Lavoie & Harris, 1991).
e) DERMAL: A 51-year-old woman used a 40% nicotine sulfate insecticide solution to treat her scabies and severe pruritus. Nausea and vomiting developed 15 minutes after application. Two hours later, she was lethargic but arousable and oriented, weak, had nausea, vomiting, and abdominal cramps. Vital signs included blood pressure (150/100), heart rate (90), respiratory rate (15, irregular with periods of apnea), miosis, and absent deep tendon reflexes. Dermal decontamination was accomplished, but plasma cotinine levels continued to rise until at least 13 hours after exposure, while nicotine levels remained constant, indicating continued dermal absorption despite decontamination. In spite of rising levels, rapid tolerance developed (Benowitz et al, 1987).

B)

1) ROUTE OF EXPOSURE

a) SMOKELESS TOBACCO: A 14-month-old boy ingested the contents of a spittoon. About 45 minutes after ingestion, the child had involuntary twitching of arms and legs, and received 10 cc of ipecac upon recommendation at about 75 minutes postingestion. On transport to the hospital, the boy was pale, cold, and clammy, listless and lethargic, and difficult to arouse. Vital signs were normal at about 2 hours postingestion. Patient received activated charcoal, which he vomited, and was observed until 1.5 hours postingestion. No further symptoms were noted (Goepferd, 1986).
b) CIGARETTE INGESTION: An 18-month-old child demonstrated a sinoauricular block following the ingestion of one-fifth of a regular cigarette (approximately 4 mg of nicotine) (Gyllensward & Nordbring, 1953).

Range Of Toxicity

Summary

A)

B)

Minimum Lethal Exposure

A)

1) Nicotine is highly toxic. About 2 to 5 mg can cause nausea. The lethal oral dose for adults has been estimated to be approximately 40 to 60 mg (Malizia et al, 1983) or 0.8 to 1.0 mg/kg in an adult (Salomon, 2006). Survival has been reported after ingestion of 1 to 4 g (Franke & Thomas, 1936).

B)

1) CASE REPORTS

a) A 24-year-old woman was found in pulseless electrical activity and had a return of spontaneous circulation after 10 minutes of CPR only (no medications administered) following the intentional ingestion (time of ingestion unknown) of liquid nicotine and whiskey. Two empty 15 mL vials of concentrated nicotine (100 mg/mL) were found near the patient and a suicide note. She was intubated in the field and arrived in the ED about 10 minutes later with fixed and dilated pupils, incontinence, hypotension (74/53 mmHg) and a pulse rate of 106 beats/min. The endotracheal tube required adjustment due to right mainstem intubation. The patient responded slightly to painful stimuli only. A comprehensive drug screen was positive for only nicotine, cotinine, and her previously prescribed medications (ie, trazodone, fluoxetine, and olanzapine). Her nicotine level obtained shortly after arrival was greater than 1000 ng/mL (measured by LC/MS/MS). She continued to have myoclonic jerking despite drug therapy and was noted to have an absence of corneal, gag or cough reflexes. An EEG was consistent with poor cerebral dysfunction. On day 2, a MRI of the brain showed multiple acute infarcts consistent with anoxic brain injury. Due to her poor prognosis, intensive treatment was stopped and the patient died 3 days after ingestion (Chen et al, 2015).
b) A 29-year-old man with a history of depression was found unresponsive after purportedly injecting himself (a suicide note was found) with an unknown amount of liquid nicotine used with an electronic delivery system. Initially, he was found pulseless and CPR was started by EMS and he was intubated in the field. Upon arrival he was in normal sinus rhythm but remained unresponsive. A short time later he developed tonic-clonic seizures and required fosphenytoin and levetiracetam to finally control the seizures. By day 5, he was diagnosed with anoxic encephalopathy and declared brain dead. A blood examination collected on the day of arrival showed a serum nicotine level of 2000 ng/mL (normal, 5 to 90 ng/mL) and cotinine was 2100 ng/mL (normal, 100 to 1200 ng/mL). Based on these blood levels, it was estimated that the patient could have injected over 400 mg of nicotine. Although an injection site was never found, the authors suggested the patient may have ingested the liquid nicotine (Thornton et al, 2014).
c) A 34-year-old man, with a history of psychosis, was found dead by his family with 3 empty vials of liquid nicotine found in his room. There was no evidence of trauma and his postmortem exam was positive for nicotine. A remaining vial (brand Titanum Ice) was tested and found to contain a nicotine concentration of 74 mg/mL. The lethal dose calculated (based on 1 mg/kg body weight) for this patient was 72.5 mg nicotine, thus the patient could have ingested a single vial (containing 50 mL of 72 mg/mL) and would have ingested approximately 50 times as high as the estimated lethal dose (Bartschat et al, 2015).

C)

1) HUMAN EXPOSURE: Nicotine sulfate is classified as super toxic. The probable oral lethal dose in humans is less than 5 mg/kg (less than 7 drops) for a 70 kg (150 pound) person (EPA, 1985).

a) Five adults who swallowed 20 to 25 g nicotine sulfate solution died within 1 hour (Baselt & Cravey, 1995).

D)

1) Amounts of 10 mg/kg administered buccally in dogs is considered potentially fatal (Franke, 1932).
2) Twenty-one of 32 chicks died when 0.07 mg/egg nicotine sulfate was administered to chick embryos at stage 11 of development (HSDB, 1997).
3) Albino rats were unable to survive on diets containing more than 0.05% nicotine sulfate (Wilson & DeEds, 1936).
4) Mortalities in bird species (eg, mallards, pheasants, coturnix, pigeons) occurred as soon as 6 minutes or as late as 2 days following treatment (HSDB, 1997).
5) The lethal dose for 18-month-old lambs has been estimated at 0.2 to 0.3 g. Toxic dose for adult sheep is 0.7 to 1 g. Poisoning in bulls and heifers from 1 year to 18 months of age occurred at a 1 g dose level (HSDB, 1997).
6) An attempt to use 1.2% solution of nicotine sulfate as tsetse-fly repellent by spraying over cattle led to deaths within 1 hour (HSDB, 1997).

Maximum Tolerated Exposure

A)

1) One regular cigarette contains 15 to 30 mg nicotine
2) One low nicotine cigarette contains 3 to 8 mg nicotine
3) One cigarette butt contains 3.75 to 7 mg nicotine
4) One cigar contains 15 to 40 mg nicotine
5) One gram snuff (wet) contains 12 to 16 mg nicotine
6) One gram chewing tobacco contains 6 to 8 mg nicotine
7) One piece of nicotine chewing gum contains 2 or 4 mg nicotine
8) One nicotine patch contains 8.3 to 22 mg nicotine
9) One nicotine nasal spray contains 0.5 mg nicotine
10) Nicotine refill cartridges used in electronic-cigarettes are available in various strengths ranging from 6 mg/mL (0.6%) to 36 mg/mL (3.6%)

1) (Gupta et al, 2014; Salomon, 2006; McGee et al, 1995; Armitage et al, 1975).
2) BIDI cigarettes, imported from India, contain cured flakes and dust of dark tobacco leaves rolled in dried tendu leaves. Despite containing less tobacco, a single bidi produces 3 times as much nicotine and carbon monoxide as the standard American cigarette. Also, the tendu leaf wrapper does not burn well; therefore, a smoker has to inhale frequently and deeply, which could result in large amount of tar being deposited into the airways (Yen et al, 2000).

B)

1) INGESTION

a) SUMMARY

1) Survival has been reported after ingestion of 1 to 4 g (Franke & Thomas, 1936).

b) ADULT

1) CASE REPORT: A 67-year-old man, with a history of cerebral infarct of the right hemisphere, intentionally ingested a nicotine extract (prepared by extracting 300 g tobacco, producing an estimated 6780 mg nicotine). The "recipe" was found on an Internet site. The patient drank the extract and immediately felt ill and vomited. Upon admission, the patient was somnolent and showed marked hyperextension of the neck and slurred speech. Tachycardia was observed, which normalized on the second day. The patient gradually improved with supportive care, and returned to baseline within 4 days (Schneider et al, 2009).
2) CASE REPORT: A 35-year-old patient developed agitation, hypertension, tachycardia, dizziness, and nausea after ingesting 7 to 20 cigarettes on 7 different occasions within 15 months. Following supportive care, he recovered and was transferred to the psychiatry department within 24 hours (Metzler et al, 2005).

c) PEDIATRIC

1) CHILDREN: More severe symptoms occur in infants (younger than 1 year) than in older children. In young children, as little as 1 mg of nicotine can produce symptoms (Salomon, 2006).
2) Studies have been conducted to quantify the amount of nicotine responsible for producing symptoms following the ingestion of cigarettes or cigarette butts in children less than 6 years of age. In one series, assuming a cigarette contains a minimum of 13 mg of nicotine, severe toxicity was reported in 3 children ingesting 1.4 to 1.9 mg/kg of nicotine (brief periods of limb twitching or unresponsiveness); children ingesting a mean of 0.8 mg/kg (range: 0.2 to 1.8 mg/kg) developed mild symptoms and children ingesting a mean of 0.5 mg/kg (range: 0.3 to 1 mg/kg) remained asymptomatic (Smolinske et al, 1988).

a) In another study, the number of cigarettes or cigarette butts reportedly ingested was found to be a poor predictor of toxicity, due in part to the difficulty in determining the actual number of cigarettes ingested or the amount of nicotine absorbed. During 1988 and 1991, a total of 700 children exposed to tobacco products were followed by the Delaware Valley Regional Poison Control Center. Of the 700 children enrolled, 44 patients ingested 2 cigarettes or 6 cigarette butts, 20 became symptomatic and all vomited. Of the remaining 24 children that were initially asymptomatic, 23 (1 was lost to follow-up) remained asymptomatic during their ED admission. Of the 656 children ingesting less than 2 cigarettes or 6 cigarette butts, 123 (18%) became symptomatic. Vomiting was observed in 89 (74.2%) of the 120 (3 were lost to follow-up) patients. Irritability and lethargy were observed in 4 children. There were no reports of seizures, coma or respiratory difficulties in any child. Children that were initially asymptomatic did not develop symptoms. The lack of early symptoms (ie, onset of vomiting within 20 minutes or less {observed in 97.9% of symptomatic children}) appeared to be a likely predictor of no subsequent toxicity (McGee et al, 1995).
b) During January 1994 to July 1996, the Rode Island Poison Control Center received 146 reports of nicotine ingestion by children less than 6 years of age, follow-up was available for 90 children (mean age: 11.7 months) with no reports of severe toxicity. Of the 50 children ingesting cigarettes, 36 ingested less than 1 cigarette, and of the 40 children ingesting a cigarette butt, 22 ingested less than 1 cigarette butt. Thirty children developed minor symptoms which included: vomiting (n=26), nausea (n=2), pallor (n=2), lethargy (n=1) and gagging (n=3). All 30 children recovered within 12 hours (None Listed, 1997).

2) LIQUID NICOTINE

a) SUMMARY

1) Electronic cigarette solutions have mean nicotine concentration of 8.5 to 22.2 mg/mL. Refills are available in 5, 10 or 20 mL vials. Based on social media sites, it has been suggested that a typical e-cigarette smoker uses on average 2 nicotine cartridges a day which is equivalent to 40 traditional cigarettes (Lowry, 2014).
2) Electronic-cigarette users frequently use refill cartridges containing liquid nicotine that are available in various strengths ranging from 6 mg/mL (0.6%) to 36 mg/mL (3.6%). It is estimated that 20 drops are equal to 1 mL of solution; 1 drop of 3.6% liquid contains 1.8 mg of nicotine. A potential ingestion of 1 to 2 drops of 3.6% solution (1.8 to 3.6 mg) could produce significant symptoms in a young child (Gupta et al, 2014).

b) CASE REPORTS

1) ADULT

a) A 24-year-old man intentionally ingested 180 mg of liquid nicotine (one capsule) used in electronic cigarettes and developed vomiting within 10 minutes of exposure. He immediately contacted an ambulance and was admitted within 30 minutes and received 3 g of activated charcoal. The patient also reported dizziness and he had slight hypertension and tachycardia. All symptoms resolved over the next 3 hours (Eberlein et al, 2014).
b) A 24-year-old man was admitted with chest pain of 4 hours duration while using liquid nicotine. He had a 1-month history of using liquid tobacco containing 16 mg of nicotine daily (approximately equivalent to 1 pack of cigarettes) and prior to that he had a 4-year history of smoking one pack of cigarettes daily. An ECG showed ST segment elevation on leads DI, aVL and V1-6 with reciprocal ST segment depression and T-wave inversion on leads a VF, DII and DIII. An echocardiogram was consistent with anterior wall hypokinesis with an ejection fraction of 50%. A troponin level was 223 pg/mL (normal range: 0 to 14 pg/mL). A thrombus in the proximal left anterior descending artery was found on cardiac catheterization. Due to his age and no underlying health conditions, the patient was treated with tissue plasminogen activator which relieved his chest pain and the ECG showed a 70% resolution of ST elevation (Kivrak et al, 2014).

2) TODDLER

a) A 30-month old child was found with a nicotine refill cartridge (strength unknown) by her mother and it was uncertain if she had ingested any of the liquid. The child vomited a short time later. Upon admission, the child was asymptomatic and was observed for 6 hours and then discharged to home with no further reported symptoms (Gupta et al, 2014).

c) CASE SERIES

1) PEDIATRIC

a) A retrospective review was conducted to assess the clinical outcomes of children 6 years of age and less that were exposed to liquid nicotine. A total of 181 cases were identified between 2009 and 2015. Symptoms developed in 47 (26%) children. Vomiting (n=39) was the most common event, followed by drowsiness (n=8), pallor (n=6), tachycardia (n=5), hypertension (n=3), coughing/choking (n=3), agitation (n=3), oral irritation (n=2), and diaphoresis (n=2). Coma was reported in one case. In 41 cases, the onset of symptoms occurred with a mean time of 18 minutes (median time, 15 minutes). One child unexpectedly vomited 2 hours after having no symptoms. Of the 31 cases that documented the duration of symptoms, 7 were defined as brief, 13 had a duration of less than 60 minutes and 11 had symptoms for 60 minutes or longer (Wilcox & Elko, 2015).

3) NICOTINE GUM

a) Nicotine chewing gum has produced toxicity following chewing of one-half to 30 pieces in children or adults (Smolinske et al, 1988; Mensch & Holden, 1984; Rigotti & Eagle, 1986; Stewart & Catterall, 1985).

4) NICOTINE TRANSDERMAL PATCH

a) BUCCAL ABSORPTION: Severe toxicity (eg, hypertension, tachycardia, vasoconstriction) has occurred via buccal absorption of a single transdermal nicotine patch, Prostep(R); volunteers bit into the patch and retained it in their mouths for 60 seconds (Harchelroad et al, 1992).
b) ADULT: Simultaneous application of 12 nicotine patches (21 mg per patch) in an adult resulted in sweating, pallor, nausea, dizziness, stupor, and obtundation within 2 hours (Woolf et al, 1996).
c) PEDIATRIC: An 11-year-old boy placed 2 transdermal nicotine patches on his skin. He became symptomatic and recovered following a fluid bolus and atropine; he was asymptomatic within 4 hours. Children are unlikely to develop symptoms with an estimated absorbed dose of less than 0.1 mg/kg (Wain & Martin, 2004).

5) NICOTINE SULFATE MIST

a) 0.2 mg/cubic meter of nicotine sulfate mist is considered the minimal concentration for poisoning (ACGIH, 1986).

Serum Plasma Blood Concentrations

7.5.1)

A) THERAPEUTIC CONCENTRATION LEVELS

1) TRANSDERMAL

a) In a comparison study to evaluate the pharmacokinetics of 2 nicotine transdermal systems (Habitrol(R) and Nicoderm(R) each to deliver 21 mg/day) in healthy male subjects (n=24), the 2 products were not found to be bioequivalent. The mean maximal nicotine plasma concentrations (Cmax) of 22.8 and 21.0 ng/mL were found to be similar after a single application. However, the mean time to maximal nicotine plasma concentration (Tmax) varied significantly between Nicoderm(R) (5.2 hr) and Habitrol(R) (9.8 hr) (Gupta et al, 1995).

1) Likewise, the plasma cotinine concentrations for the 2 products were found to be similar after a single application, but the steady state kinetics were 10% lower for Habitrol(R) (290.5 ng/mL) compared to Nicoderm(R) (322.5 ng/mL). In addition, cotinine Tmax values for the 2 products were found to be similar after a single application (Gupta et al, 1995).

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CONCENTRATION LEVEL

a) Nicotine is highly toxic. About 2 to 5 mg can cause nausea. The lethal oral dose for adults has been estimated to be approximately 40 to 60 mg (Malizia et al, 1983). Survival has been reported after ingestion of 1 to 4 g (Franke & Thomas, 1936).
b) Ingestion of an unknown amount of nicotine alkaloid with a concentration of 870 mg/mL resulted in a fatal nicotine serum level of 13,600 nanograms (ng)/mL (Lavoie & Harris, 1991).
c) COTININE: Vlachos et al (1992) reported concentration of cotinine in urine as high as 653 ng/mL at 3 hours after ingestion of cigarettes in a study of 20 infants. Mild symptoms (eg, vomiting, slightly elevated blood pressure, and tachycardia) were noted in 5 of 20 cases.
d) LIQUID NICOTINE: A 34-year-old man, with a history of psychosis, was found dead by his family and 3 empty vials of liquid nicotine were found. There was no evidence of trauma and his postmortem exam was positive for nicotine. A remaining vial (brand Titanum Ice) was tested and found to contain a nicotine concentration of 74 mg/mL. The lethal dose calculated (based on 1 mg/kg body weight) for this patient was 72.5 mg nicotine, thus the patient could have ingested a single vial (containing 50 mL of 72 mg/mL) and would have ingested approximately 50 times as high as the estimated lethal dose (Bartschat et al, 2015).
e) NICOTINE EXTRACT: Intentional ingestion of a nicotine extract (prepared by extracting 300 g of tobacco, producing an estimated 6780 mg of nicotine) by a 67-year-old man resulted in a peak serum concentration of nicotine and cotinine of 386 mcg/L and 9955 mcg/L, respectively. No permanent sequelae occurred. The authors suggested that the patient only absorbed a small portion of the extract, due to immediate vomiting. Residue of the extract was also found near the patient after ingestion (Schneider et al, 2009).
f) TRANSDERMAL: Application of multiple nicotine patches in addition to smoking cigarettes resulted in a plasma nicotine level of 3.7 mcg/mL about 11 hours following a cardiac arrest in a 32-year-old man (Sanchez et al, 1996).
g) TRANSDERMAL: Serum nicotine and cotinine levels were reported to be 27 ng/mL and 390 ng/mL, respectively, in a 37-year-old man after application of 12 nicotine patches (21 mg each) in an apparent suicide attempt (Woolf et al, 1996).
h) CHILDREN: More severe symptoms occur in infants (younger than 1 year) than in older children. As little as 1 mg of nicotine (Goldfrank et al, 1998), or 0.2 mg/kg can produce symptoms in a small child (Wain & Martin, 2004). Children will probably not develop symptoms with an estimated absorbed dose of less than 0.1 mg/kg (Wain & Martin, 2004).
i) Assuming that 1 cigarette contains a minimum of 13 mg, severe toxicity was seen after 1.4 to 1.9 mg/kg, mild toxicity after 0.2 to 1.8 mg/kg, and no toxicity after 0.3 to 1 mg/kg (Smolinske et al, 1988).

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Nicotine

a) TLV:

1) TLV-TWA: 0.5 mg/m(3)
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: Not Listed
2) Codes: Skin
3) Definitions:

a) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s): GI dam; CNS impair; card impair
d) Molecular Weight: 162.23

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS54-11-5 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Nicotine
2) REL:

a) TWA: 0.5 mg/m(3)
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: [skin]

1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.

f) Note(s):

3) IDLH:

a) IDLH: 5 mg/m3
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS54-11-5 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Nicotine
2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Nicotine
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS54-11-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Nicotine
2) Table Z-1 for Nicotine:

a) 8-hour TWA:

1) ppm:

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 0.5

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: Yes
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) NICOTINE

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 5900 mcg/kg

2) LD50- (ORAL)MOUSE:

a) 3340 mcg/kg

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 16 mg/kg

4) LD50- (INTRAPERITONEAL)RAT:

a) 14,560 mcg/kg

5) LD50- (INTRATRACHEAL)RAT:

a) 19,300 mcg/kg

6) LD50- (ORAL)RAT:

a) 50 mg/kg

7) LD50- (SKIN)RAT:

a) 140 mg/kg

8) LD50- (SUBCUTANEOUS)RAT:

a) 25 mg/kg

B) Nicotine sulfate

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 10,200 mcg/kg

2) LD50- (ORAL)MOUSE:

a) 8550 mcg/kg

3) LD50- (ORAL)RAT:

a) 50 mg/kg

4) LD50- (SKIN)RAT:

a) 285 mg/kg

Pharmacology Toxicology

Pharmacologic Mechanism

A)

B)

1) Physiologic effects include peripheral nervous system stimulation followed by depression of sympathetic and parasympathetic ganglia and neuromuscular junctions.
2) Central nervous system stimulation of respiration, stimulation of the medulla oblongata leading to vomiting and antidiuretic action.
3) Stimulation followed by BLOCKADE of autonomic ganglia, inhibition of catecholamines, and subsequent CNS depression.

C)

1) CARDIOVASCULAR: Stimulation of sympathetic ganglia and adrenal medulla leading to release of catecholamines.
2) GASTROINTESTINAL: Parasympathetic stimulation leading to increased tone and motor activity.

Physicochemical

Physical Characteristics

A)

B)

C)

D)

E)

F)

G)

Ph

A)

B)

C)

Molecular Weight

A)

Animal Toxicology

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

1) Begin treatment immediately.
2) Keep animal warm.
3) Sample vomitus, blood, urine, and feces for analysis.
4) If skin exposure has occurred, wash animal thoroughly with a mild detergent and flush with copious amounts of water.

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) SMALL ANIMALS

a) Gastric lavage may be performed using tap water or normal saline.
b) Administer activated charcoal, 5 to 50 g orally, as a slurry in water.
c) Then administer Milk of Magnesia 1 to 15 mL orally, mineral oil 2 to 15 mL orally, sodium sulfate 20%, 2 to 25 g orally, or magnesium sulfate 20%, 2 to 25 g orally, for catharsis.
d) Emesis may be dangerous, due to rapid onset of symptoms. Multiple-dose activated charcoal may be of use. Symptomatic care for hypotension or hypertension and for seizures should be given.

2) LARGE ANIMALS

a) Give 250 to 500 g activated charcoal in a water slurry, orally, to adsorb the toxic agent.
b) Administer an oral cathartic: mineral oil (1 to 3 L), 20% sodium sulfate (25 to 10,000 g), 20% magnesium sulfate (25 to 1000 g), or Milk of Magnesia (20 to 30 mL).
c) Emesis may be dangerous, due to rapid onset of symptoms. Multiple-dose activated charcoal may be of use. Symptomatic care for hypotension or hypertension and for seizures should be given.

Clinical Effects

11.1.13)

A) OTHER

1) Initial hyperexcitability, hyperpnea, salivation, vomiting, diarrhea, then depression, incoordination, and paralysis.

Treatment

11.2.1)

A) GENERAL TREATMENT

1) Begin treatment immediately.
2) Keep animal warm.
3) Sample vomitus, blood, urine, and feces for analysis.
4) If skin exposure has occurred, wash animal thoroughly with a mild detergent and flush with copious amounts of water.

11.2.4)

A) GASTRIC DECONTAMINATION

1) SMALL ANIMALS

a) Gastric lavage may be performed using tap water or normal saline.
b) Administer activated charcoal, 5 to 50 g orally, as a slurry in water.
c) Then administer Milk of Magnesia 1 to 15 mL orally, mineral oil 2 to 15 mL orally, sodium sulfate 20%, 2 to 25 g orally, or magnesium sulfate 20%, 2 to 25 g orally, for catharsis.
d) Emesis may be dangerous, due to rapid onset of symptoms. Multiple-dose activated charcoal may be of use. Symptomatic care for hypotension or hypertension and for seizures should be given.

2) LARGE ANIMALS

a) Give 250 to 500 g activated charcoal in a water slurry, orally, to adsorb the toxic agent.
b) Administer an oral cathartic: mineral oil (1 to 3 L), 20% sodium sulfate (25 to 10,000 g), 20% magnesium sulfate (25 to 1000 g), or Milk of Magnesia (20 to 30 mL).
c) Emesis may be dangerous, due to rapid onset of symptoms. Multiple-dose activated charcoal may be of use. Symptomatic care for hypotension or hypertension and for seizures should be given.

References

General Bibliography

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FeedBack

NICOTINE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Genitourinary

Dermatologic

Musculoskeletal

Immunologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Methods

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Life Support

Patient Disposition

Monitoring

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Pharmacologic Mechanism

Physical Characteristics

Ph

Molecular Weight

Continuing Care

Clinical Effects

Treatment

General Bibliography