The Perioperative Implications of Tobacco, Marijuana, and Other Inhaled Toxins

Ethan O. Bryson, MD Elizabeth A.M. Frost, MD

Mt Sinai Medical Center New York

Introduction

Inhalation of many substances has been part of civilization for thousands of years, both for pleasure and medicinal reasons. Abuse of this practice is also indigenous to our society. Although tobacco is probably the most abused inhalant, many other agents have been sniffed and taken in through the respiratory tract by all segments of our population.

Tobacco
Background and Trends

The past decade has witnessed an aggressive antismoking campaign that has resulted in the passage of laws in many states banning the practice in public places. Dramatic increases in taxation have been enacted in an attempt to further place these items out of reach of the majority of consumers. In addition, large nes and settlements have been leveled against the tobacco industry as compensation for health damages and false advertising. The Family Smoking and Prevention and Tobacco Control Act was signed into law in June 2009 and granted the

REPRINTS: ETHAN O. BRYSON, MD, MOUNT SINAI HOSPITAL, ONE GUSTAVE L. LEVY PLACE, DEPARTMENT ANESTHESIOLOGY BOX 1010, NEW YORK, NY, 10029, E-MAIL: ETHAN.BRYSON@MOUNTSINAI.ORG
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Food and Drug Administration extensive authority to regulate tobacco products. The tobacco industry led a suit in August 2009 challenging the constitutionality of the advertising and promotion restrictions of this law. The legal arguments and ramications from both sides are considerable.1 Unfortunately, because of the highly addictive nature of nicotine, what may be seen as a luxury to the nonsmoker can easily become a necessity to the regular smoker. Despite these drastic measures, cigarette smoking remains the number one preventable cause of morbidity and mortality in the United States as well as several other countries in the world.2 As of 2008, approximately 1 in 5 US adults (46.0 million persons) was a regular cigarette smoker. Although there is a signicant downward trend in the total number of adult smokers, the morbidity and mortality associated with cigarette smoking still affects more people in this country than any other drug of abuse.3
Components of Cigarette Smoke

First manufactured in the 1950s in an attempt to produce a healthier cigarette, current cigarette lters are made primarily of cellulose acetate tow and reduce the amount of tar and nicotine present in mainstream smoke by 40% to 50% as compared with nonlter cigarettes.4 Sill, the smoke inhaled by the smoker, contains several thousand compounds in both the particulate and the gas phase, many of which are known toxins and carcinogens.5 Known carcinogens in cigarette smoke include tar, the particulate matter which is not nicotine, polynuclear aromatic hydrocarbons, b-naphthylamine, benzopyrene, nitrosamines, vinyl chloride, and trace metals, to name a few. Tumor accelerators present in cigarette smoke include indole and carbazole. Ciliotoxins such as ammonia and formaldehyde are not removed in appreciable quantities by lters.
Effects on the Pulmonary System

Smoking has several detrimental effects on pulmonary function. The degree to which any individual smoker is affected depends upon both the length of time the patient smoked and the degree of smoking as measured in number of cigarettes smoked per day. Heavier smokers who have smoked for periods of time measured in years rather than months are more likely to develop pulmonary complications postoperatively, but even the social or light smoker may be at increased risk. Children especially who are subject to second hand smoke are also at risk for development of asthma. Alterations in central airways that increase the risk for complications include loss of cilia, mucus gland hyperplasia, and an increased number
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of goblet cells leading to an overproduction of mucus, not easily cleared from the lungs. As a result, smokers are more likely to have a chronic cough and are more prone to dyspnea with exertion. Histologically, regression of normal pseudostratied ciliated epithelium and squamous metaplasia portend the development of carcinoma in-situ, eventually leading to invasive bronchogenic carcinoma. Alterations in peripheral airways that increase the risk for complications include inammation and atrophy, causing goblet and squamous cell metaplasia, the end result of which is mucous plugging and smooth muscle hypertrophy. Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality associated with heavy smoking. Surprisingly, most smokers do not develop clinically signicant COPD. However, as the number of smokers is so large, death by COPD caused by cigarette smoking remains the fourth leading cause of death in this country.6
Effects on the Cardiovascular System

The pathologic effects of smoking on the cardiovascular system are many. Injury to the vascular intima, thought to be directly caused by nicotine, can initiate the development of atherosclerosis in younger patients with no other risk factors. For patients who already have atherosclerosis, the injury caused by smoking hastens progression of the disease. Carbon monoxide increases smooth muscle cell proliferation that can exacerbate the physiologic effects of nicotine on the body and eventually lead to cardiomyopathy. The physiologic effects of smoking are evident once tobacco smoke enters the body. Heart rate and cardiac output both increase. Vasoconstriction of peripheral arteries increases peripheral vascular resistance and blood pressure. Vasoconstriction of coronary arteries impairs ow regulation. The increased stress placed on the heart increases myocardial oxygen demand and may lead to ischemia in patients with coronary artery disease. In patients at risk, the incidence of dysrhythmias increases. The threshold for ventricular brillation decreases. These effects are primarily caused by the stimulant effects of nicotine and dissipate 15 to 30 minutes after cessation of inhalation, because of the relatively short plasma half-life of the substance. An association between cerebral aneurysms and smoking has long been recognized with approximately 66% of patient presenting with ruptured aneurysms and currently smoking.7 Indeed, smoking is the most modiable risk factor for the formation and rupture of intracranial aneurysms. Other studies have found evidence of a gene environment interaction with smoking and intracranial aneurysm rupture.8 Cause may be related to repeated episodes of hypoxia that weakens the cerebral vasculature where aneurysms are most likely to develop.
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Effects on the Hematologic System

Smoking increases the release of platelet factors such as thromboxane that activate the atherosclerotic process. Increased platelet aggregation and adherence to endothelium, coupled with increased levels of brinogen and factor VII levels causes clot and microemboli formation. Plasma viscosity is increased by chronic exposure to increased levels of carbon monoxide. Owing to the decreased release of prostacyclin, the effect of aspirin on platelets is decreased and bleeding times are lower as blood clots more readily. Red blood cells become less deformable and are more likely to cause obstructions in the microcirculation. Platelet survival time decreases.
Metabolic Effects

Smoking increases the level of serum free fatty acids and low-density lipoprotein cholesterol, and decreases levels of serum high-density lipoprotein cholesterol, which likely contributes to the development or acceleration of atherosclerosis. Growth hormone, cortisol, glucose, antidiuretic hormone, glycerol, lactate, and pyruvate levels are all increased. Decreased serum estrogen, leading to earlier menopause, has also been observed.
Perioperative Management

Ideally, complete abstinence from cigarette smoking is achieved before surgery to allow the regrowth of cilia and recovery of full pulmonary function. As this requires at least 8 weeks9 and the preanesthetic assessment is rarely performed more than a week before the scheduled date of surgery (and often only minutes before entering the operating room), this ideal state is not usually realized. If the preanesthetic assessment is performed the day before surgery, the patient should be advised to abstain for a minimum of 12 hours before receiving anesthesia to allow for the elimination of nicotine and carboxyhemoglobin. A carboxyhemoglobin level of 15% can reduce the availability of oxygen by up to 25% and presents a considerable risk for patients with coronary artery disease. In this population, it may be justiable to postpone a case if the patient reports smoking just before surgery. A recent study has suggested that surgery might be an opportune time to quit smoking. In a review of 5498 smokers, 2444 quit smoking during surgery.10 Twenty one percent quit at follow-up after major surgery and 10% stopped after out patient surgery. Eight percent of quit events in the US are associated with surgery and thus counseling during preanesthetic assessment may be a worthwhile teachable and even billable event.
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The development of hyperreactive airways in the chronic smoker is a major cause for complications that develop under anesthesia. Cholinergic drugs or drugs that cause histamine release can trigger acute episodes of bronchospasm. Even the physical stimulus caused by hyperventilation before intubation or the presence of an endotracheal tube in the trachea can trigger bronchospasm. Smokers can be exquisitely sensitive, even if they have no past medical history signicant for reactive airway disease. As such, great care should be taken to avoid the use of cholinergic agents and the anesthesia provider should maintain a heightened awareness of the possibility that bronchospasm may occur. Despite the observation that aerosols can trigger episodes of bronchospasm particularly in sensitive patients, premedication with albuterol or with combined corticosteroids and salbutamol has been shown to reduce the possibility for intubation-evoked bronchoconstriction.11 Premedication with glycopyrrolate may reduce the copious mucus secretions typically seen in the smoker who presents for surgery. The addition of humidied fresh gas through the breathing circuit may also help, though thick mucus secretions may still develop. High on the differential diagnosis for the smoker who develops high peak airway pressures during general anesthesia is the development of an obstructive mucus plug in the endotracheal tube. Often the placement of a suction catheter down the endotracheal tube is both diagnostic and therapeutic. Adequate postoperative pain management is of particular importance, especially for the smoker who has just undergone a large intraabdominal procedure. These patients are entirely dependent upon their coughing mechanism to clear pulmonary secretions, and pain associated with respiratory effort could lead to atelectasis, worsening of existing shunt physiology, hypoxia, and possibly postobstructive pneumonia. If routine chest physiotherapy is ineffective and systemic opioid administration interferes with the ability to adequately clear secretions, the anesthesia team should consider placement of an epidural catheter for pain management.

Marijuana
Background and Trends

The female plant of Cannabis sativa, specically the dried owers or buds, has been ingested for centuries for recreational or medicinal purposes and as part of certain religious ceremonies. Marijuana use is common in our society, and as recently as 2001, it was estimated that 10% to 20% of patients between the ages of 18 and 25 years regularly use the drug.12 Although the primary psychoactive component is d-9
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tetrahydrocannabiol (THC), over 60 other compounds, some with psychoactive properties have been identied in the plant and have the potential to contribute to the adverse effects associated with acute or chronic abuse.13 THC and other cannabinoids are rapidly absorbed through the lungs, producing a wide range of psychologic and central nervous system (CNS) effects that peak in 15 minutes and persist for 2 to 4 hours depending on the dose. Users report feelings of euphoria, heightened sensory perception, and a distortion of space and time. In some patients, these sensations are anxiety provoking and some have reported feelings of dysphoria. In patients with underlying psychiatric disorders, aggravation of psychotic states has been reported. Generalized CNS depression leading to drowsiness and sleep typically follows the initial psychomotor agitation. When cannabis is ingested orally, the bioavailability is variable but considerably lower because of issues with absorption and rst pass metabolism by the liver. Onset of effects is slower and may persist for a longer period of time.14 Multiple attempts have been made to delineate the therapeutic uses of cannabinoids and they have been used with varying success in the treatment of spastic disorders, chronic pain, epilepsy, glaucoma, bronchial asthma, as an antiemetic, and an appetite stimulant. Benecial effects of marijuana ingestion include mild analgesia similar in its effectiveness to codeine, antiemetic effects, though tolerance to this effect dose develop, and increased appetite.
Toxic Effects

Marijuana is typically ingested by inhalation, with the same symptoms of coughing, increased sputum production, and occasional wheezing associated with acute inhalation of tobacco smoke. Chronic marijuana smokers, despite popular belief to the contrary, are also at increased risk for the development of lung cancer. Possibly owing to the practice of deeply inhaling and breath holding when smoking marijuana to maximize THC absorption, patients with a history of heavy cannabis use have developed cancer of the throat and lungs at a much younger age than chronic tobacco smokers.15 Despite the potential benet of THC as a bronchodilator, pulmonary complications in the chronic smoker are equivalent to those seen in the chronic tobacco smoker, likely due to the other constituents of marijuana smoke. Although marijuana smoke contains roughly the same amount of carbon monoxide from incomplete combustion of organic compounds as tobacco smoke, the typical marijuana smoker holds smoke in their lungs much longer, resulting in levels of carboxyhemoglobin up to 5 times that of the typical tobacco smoker.16 This practice of deep inhalation and breath holding exposes the smoker to increased levels of
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the same carcinogens and pulmonary toxins found in tobacco smoke and is responsible for the development of complications in the chronic user. Intoxication with marijuana decreases blood pressure because of vasodilation and increases heart rate, leading to an increased cardiac output and increased myocardial demand for oxygen. These effects on the cardiovascular system have the potential to interfere with medications administered throughout the course of an anesthetic and may cloud the interpretation of intraoperative physiologic data. The potential for ischemic events in young healthy patients is small, although for patients at risk it is increased when anesthesia is administered to the acutely intoxicated patient.17
Perioperative Management

An interaction between cannabinoids and anesthetic agents, specically additive effects in the acutely intoxicated patient and the development of cross-tolerance in the chronic user, has long been postulated. Recently, a study examining the induction dose of propofol in chronic cannabis users and patients with no history of cannabis use suggests that such an interaction is likely. In this study, chronic users required clinically signicant increased doses of propofol to facilitate laryngeal mask airway placement.18 Possible tolerance to other anesthetic agents should be considered when a history of marijuana use is elicited. The existence of one case report of airway obstruction in a patient who reported smoking marijuana 4 hours before surgery19 underscores the necessity of eliciting a complete history of substance use during the preanesthetic interview. The anesthesia care provider should anticipate the possibility for airway hyperreactivity in the marijuana smoker in much the same manner that such complications are anticipated in the tobacco smoker.

Nitrous Oxide
Background and Trends

In 1798, Sir Humphrey Davy,20 who was the superintendent of the Medical Pneumatic Institution founded by Thomas Beddoes at Bristol, performed considerable research on a gas identied by Joseph Priestley21 as nitrous oxide. Although Davy, almost as an aside after much experimentation on himself recognized that as nitrous oxide in its extensive operation seems capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place, he developed the gas as an agent for
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enjoyment and merriment.22 As such, it was widely acclaimed by many notoraries in England as an excellent gas that promoted both joy and strength and as such could cure many diseases. James Woodhouse, an American professor of chemistry from the University of Pennsylvania, traveled to England in 1802 and met with Davy.23 He returned to the United States and undertook extensive trials on the effects of the gas, the results of which were soon enveloped by traveling showmen such as Gardner Quincy Colton. In the famous display, witnessed by Horace Wells24 on December 10, 1844, a drugstore clerk, Samuel Cooley (Fig. 1), inhaled quantities of the gas and became rowdy, injuring himself without appreciating the pain. Wells recognized the analgesic properties and the next day applied nitrous oxide to himself for dental extraction. Nitrous oxide remained for many years as an addiction mainly of dentists as the agent was considered safe, allowing sufcient analgesia for dental work but not enough for surgical procedures. As such dentists had easier access, a situation that is still recognized today.25 However, the American philosopher, William James, used nitrous oxide extensively, noting that it allowed Thought deeper than speech! Oh God.

Figure 1. Gardner Quincy Colton (1814 to 1898). The gas used in these lectures by Dr Colton was contained in a rubber bag, and was administered through a horrible wooden faucet, similar to the contraptions used in country cider barrels. It was given in quantities only sufcient to exhilarate or stimulate the subjects, and reacted upon them in divers and sundry ways. Some danced, some sang, others made impassioned orations, or indulged in serious arguments with imaginary opponents, whereas in many instances the freaks of the subjects were amazingy From Tercentenary Commission of the State of Connecticut. The Discoverer of Anaesthesia: Dr Horace Wells of Hartford Tercentenary Commission. Yale University Press, 1933.
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My God, Oh God. Oh God ythe passport that allowed .yto see religion from the believers perspective, traveling between the worlds of science and faith.26 Today there is ready, legal and inexpensive access to nitrous oxide as it is widely used as the propellant for whipped cream. Pre-lled pressurized cans are available for sale without restriction at any grocery store and small canisters of the gas under pressure are sold in bulk for use by professional caterers and amateur chefs. These small canisters called whip-its are routinely sold at head shops along with crackers (small metal or plastic tubes in which the canister is placed allowing the user to crack the aluminum seal and access the gas) and balloons used to trap and warm the gas before inhalation. On account of this availability, it is likely that the abuse of nitrous oxide is wider than is believed.
Toxic Effects

That nitrous oxide is addictive has been demonstrated for over 200 years. Pharmacologic evidence suggests that there is direct interaction with the endogenous opioid system including a possible partial agonist effect at the mu, kappa, and sigma opioid receptors.27 Other animal studies have shown a decrease of b-endorphine in rat brain after nitrous oxide withdrawal which may account for the post-anesthesia excitatory syndrome seen in man.28 For many years nitrous oxide was believed to have no toxicity other than that associated with its anesthetic action. However, bone marrow depression in patients administered nitrous oxide for extended periods of time and neurologic abnormalities in healthcare workers who inhaled the gas recreationally have been documented.29 Retrospective surveys of dental and medical personnel have linked occupational exposure to nitrous oxide with a number of health problems and reproductive derangements. The agent reacts with the reduced form of vitamin B12, inhibiting the action of methionine synthase, an enzyme that indirectly supports methylation reactions and nucleic acid synthesis. Many, if not all, of its nonanesthetic-related adverse effects may be ascribed to this action. Animal and human studies indicate that toxic effects are concentration and time-dependent. A time-weighted average of no more than 100 parts per million for an 8-hour workday and/or a timeweighted average of 400 parts per million per anesthetic administration should provide adequate protection of dental personnel and be achievable with existing pollution control methods. Other studies have documented damage to the nervous system of chronic abusers.30 Multimodal evoked potentials (EPs) were used to evaluate the electrophysiologic abnormalities in a man who had used 4 to 5 cans of nitrous oxide (about 2000 mL/can) for more than 10 years. He complained of progressive motor disability and paresthesias in all
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limbs. Laboratory studies showed increased megaloblastic red blood cells and decreased vitamin B12 concentration. Subacute combined degeneration in the posterior and lateral cervical columns were seen on magnetic resonance imaging. Multimodal EPs showed abnormal visual EPs with prolonged peak latencies, abnormal brainstem EPs with delayed wave V, and abnormal somatosensory EPs with signicant decreased peak amplitudes. The authors indicated that abuse of nitrous oxide indirectly involves multiple levels of the nervous system. Several other reports have described spinal myoclonus,31 acute paralysis of the lower limbs,32 cervical myelopathy,33 and severe posterior column myelopathy identied by magnetic resonance imaging and EPs.34 Treatment with methionine and vitamin B12 in most cases resulted in at least partial reversal of the neurologic difculties. Other injuries that have been described include sudden lung collapse due to expansion of an asymptomatic pneumothorax.35 Such a complication presents as sudden chest pain and unless that history is elicited, the underlying problem may go undiagnosed. Exposure of the skin to nitrous oxide in abusers may cause burns and is a rare complication.36
Perioperative Management

In (usually young) patients presenting with abnormal neurologic symptoms for which there is no immediate, recognizable cause, the possibility of nitrous oxide abuse should be ruled out. Diagnosis is made by history of exposure, coupled with laboratory ndings of megaloblastic anemia and vitamin B12 deciency. As nitrous oxide is rarely the sole drug of abuse and is often present at raves and gatherings where other drugs are commonly available, the use of additional recreational drugs should be investigated. If long-standing myelopathy has already become established, there is no evidence that addition or avoidance of nitrous oxide during anesthesia is signicant. Therapy with methionine and vitamin B12 should be started immediately and psychiatric counseling instituted.

Volatile Compounds

In addition to agents produced for the purpose of recreational inhalation, there exist a number of readily obtained and easily abused volatile compounds with the potential to complicate an anesthetic. Household items such as air freshener, nail polish remover, model glue, and even mothballs have documented abuse potential.37 Acute intoxication with these agents can reduce anesthetic requirements and chronic abuse has been associated with organ system damage leading to a number of potential complications.
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Background and Trends

The recreational inhalation of volatile agents continues to be a problem in the United States, particularly among adolescents.38 These agents are relatively easy to obtain (they are inexpensive, legal, and have legitimate use) and tend to disproportionately afict vulnerable groups such as adolescents, low-income populations, and the mentally ill.39 Chronic users can become dependant upon inhalants as with other drugs of abuse and they exhibit tolerance, requiring greater amounts of agent to achieve the desired state of intoxication. Addicted individuals report increased levels of irritability, anxiety, and cravings that interfere with the activities of daily life.40 Although it is not recognized by the Diagnostic and Statistical Manual of Mental Disorder-IV, inhalant withdrawal syndrome has been reported in the literature.41 Despite their ubiquitous nature, inhalants are the least studied of all the drugs of abuse and the mechanism of action has not yet been elucidated. Prior investigations have focused on the potential for inhaled agents to interact with g-aminobutyric acid-gated chloride channels42 and 5-hydroxytryptamine type 3 receptors,43 and have shown these agents to exhibit nonselective actions on a number of ion channels in much the same manner as volatile anesthetics.44 Exposure to inhalants activates mesolimbic dopamine neurons, and may be the mechanism whereby the drug activates reward pathways to encourage abuse. Patients who abuse volatile agents typically do so with the intent to quickly reach an intense level of intoxication, achieved by inhaling concentrated vapors in an enclosed space using a variety of methods. Those new to the practice or who are experimenting may simply inhale deeply over an open container, snifng the agent in an attempt to become intoxicated. The practice of bagging involves placing the volatile agent into a plastic or paper bag and placing the bag over the nose and mouth while hyperventilating. Patients who abuse volatile agents in this manner may have telltale traces of the agent, which is paint or glue, around the mouth and nose. Hufng involves soaking a piece of cloth, often a sock, in the agent of choice and holding it up to the mouth so that the vapors are inhaled orally. When performed alone, if the agent soaked cloth does not fall away from the mouth once the patient becomes intoxicated, there exists a very real danger for overdose and death. Recreational use has been reported as a group activity, and the practice of holding the agent soaked cloth over the mouth of another, forcing them to inhale the vapors, can also prove fatal. When abused in this manner, blood levels of the volatile agent rapidly rise and create an intense feeling of euphoria, which quickly dissipates as the lipophilic agents are redistributed from the CNS to fat (Table 1).
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Table 1. Commonly Abused Chemicals and the Products That Contain Them Aliphatic hydrocarbons Cigarette lighter uid (butane) Bottled fuel (propane) Gasoline (octane) Model glues (hexane) Rubber cement (hexane) Aromatic hydrocarbons Mothballs (naphthalene) Toilet bowl freshener Resins (benzene) Gasoline (benzene) Lacquers (benzene) Adhesives (toluene) Spray paint (toluene) Paint thinner (toluene) Alkyl halides Dry cleaning agent (trichloroethylene) Spot remover (trichloroethylene) Freon (trichlorouoromethane) Aerosol propellant (trichlorouoromethane) Alkyl nitrates Room air freshener (butyl-isobutyl nitrate) Coronary vasodilator (amyl nitrate) Ethers Laboratory solvent (diethyl ether) Anesthetic agents (halogenated ethers) Ketones Nail polish remover (acetone) Paints (methyl n-butyl ketone) Spray paint (methyl isobutyl ketone)

Toxic Effects

Although the exact mechanism of action has not been determined, volatile agents are known to act as CNS depressants. Being lipophilic and easily able to cross the blood-brain barrier, these substances have the potential to cause widespread damage throughout the CNS and peripheral nervous system, and chronic abusers may develop permanent neurologic damage. Naphthalene, benzene, and toluene are all aromatic hydrocarbons found in common household items such as mothballs, toilet bowl freshener, resins, lacquers, adhesives, spray paint, and paint thinner. Of these, toluene, a typical constituent of adhesives, is thought to be the
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most toxic agent. Specic sequelae of toluene abuse include cognitive dysfunction, dementia, and an induced encephalopathy associated with euphoria, hallucinations, and nystagmus, eventually leading to seizures and coma.38 Cranial nerve damage, although rare, has also been associated with toluene abuse. Sensorimotor peripheral neuropathy, slurred speech, ataxia, and coma are further complications making informed consent difcult to obtain Direct injury to pulmonary tissues can occur as inhaled agents contact the sensitive respiratory epithelium. In addition to the development of a chemical pneumonitis, interference with the ability of the anesthetic gas analyzer to accurately measure end-tidal anesthetic concentrations in chronic abusers of the aliphatic hydrocarbons has been reported.45 Bronchospasm can occur in patients with a history of asthma and even in chronic abusers with no history of reactive airway disease. Inhaled vapors may displace oxygen within the alveoli leading to asphyxiation. The effects of the abused volatile agents are similar regardless of chemical structure, and depend primarily on the amount of agent. At lower doses peripheral vasodilatation occurs, with resultant compensatory tachycardia and the potential for orthostatic hypotension. Despite the mildly increased heart rate, decreased myocardial contractility contributes to hypotension. At higher doses bradycardia, decreased cardiac output, and sudden sniff death syndrome may occur. First reported in 1970,46 sudden snifng death occurs when the abuser is startled while under the inuence of any number of inhalants. The hypothesized mechanism is death because of the malignant dysrhythmia induced by an acute catecholamine surge in a patient whose myocardium has been sensitized to epinephrine by hydrocarbon inhalation. Common toxic effects on the gastrointestinal system include nausea, vomiting, and diarrhea. Hydrocarbons are known hepatotoxins and chronic abusers have the potential to develop transaminitis and hepatitis. Renal tubular acidosis and glomerulonephritis have also been reported in the literature.
Perioperative Management

To properly care for the inhalant abuser, the anesthesia care provider must rst identify the problem during the preanesthetic interview. Given the ubiquitous nature of these chemicals and the propensity of adolescents to experiment with them, it is likely that the actual number of patients in this population who routinely abuse inhalants is underreported. The anesthesia care provider should have a high index of suspicion for inhalant abuse when interviewing patients in high-risk categories, such as socially isolated, adolescent or young adult patients with a history of polysubstance abuse or psychiatric disorders.47
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Most often these patients come to medical attention for unrelated issues and the only evidence of chronic inhalant abuse is abnormal values on routine preanesthetic laboratory work. Anemia, leukopenia, leukemia, and aplastic anemia, although rare, are recognized sequelle of inhalant abuse and may be evident.48 In elective cases where abnormal results on preoperative studies are obtained, it may be prudent to reschedule the procedure or surgery pending further evaluation. It is also recommended that patients remain abstinent during this period of time and be referred to an appropriate addiction treatment center. Before receiving anesthesia, repeat laboratory tests should be performed to conrm normalization of values. Hepatic and renal damage in chronic abusers may decrease clearance of anesthetic agents, therefore care should be taken when providing general anesthesia using volatile anesthetics. Inhalants and volatile anesthetic agents may have similar mechanisms of action so acute intoxication may decrease the minimum alveolar concentration required to achieve a level of anesthesia adequate for surgery, whereas chronic abuse may actually increase minimum alveolar concentration. Acute and chronic inhalation of aliphatic and aromatic hydrocarbons may confound anesthetic gas analyzers and inhalants may cause airway irritation, leading to airway hyperreactivity. These problems are more likely to occur when the patient presents for surgery in the acutely intoxicated state.

Conclusions

The abuse of inhaled agents of any kind has the potential to cause damage to every human organ system and puts the patient at risk for death, either from disease related to chronic exposure or physiologic perturbations during acute intoxication. The implications for the anesthesia care provider are many and proper management of these patients begins with obtaining a history of substance abuse.

References

1. Bayer R, Kelly M. Tobacco control and free speechan American dilemma. New Engl J Med. 2010;362:281283. 2. US Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, CDC; 2004. 3. Dube SR, Asman K, Malarcher A, et al. Cigarette smoking among adults and trends in smoking cessation United States 2008, Centers for Disease Control and Prevention. Morb Mortal Wkly Rep. 2009;58:12271232. 4. Shin HJ, Sohn HO, Han JH, et al. Effect of cigarette lters on the chemical composition and in vitro biological activity of cigarette mainstream smoke. Food Chem Toxicol. 2009;47:192197.
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5. Adams J, OMara-adams K, Hoffmann D. Toxic and carcinogenic agents in undiluted mainstream smoke and sidestream smoke of different types of cigarettes. Carcinogenesis. 1987;8:729731. 6. US Department of health and human services. National Heart Lung and Blood Institute. Chronic Obstructive Pulmonary Disease. Bethesda, MD: HIH Publication No. 03-5229; 2003. 7. Sauerbeck LR, Homuung R, Moonaw CJ, et al. The effects of study participation in the familial intracranial aneurysm study on cigarette smoking. J Stroke Cerebrovasc Dis. 2008;17:370372. 8. Woo D, Khoury J, Haverbusch MM, et al. Smoking and family history and risk of aneurismal subarachnoid hemorrhage. Neurology. 2009;72:6972. 9. Warner MA, Diverti MR, Tinker JH, et al. Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients. Anesthesiology. 1984; 60:380383. 10. Shi Y, Warner DO. Surgery as a teachable moment for smoking cessation. Anesthesiology. 2010;112:102107. 11. Silvanus MT, Groeben H, Peters J. Corticosteroids and inhaled salbutamol in patients with reversible airway obstruction markedly decrease the incidence of bronchospasm after tracheal intubation. Anesthesiology. 2004;100:10471048. 12. Kumar RN, Chambers WA, Pertwee RG. Pharmacological actions and therapeutic uses of cannabis and cannabinoids. Anesthesia. 2001;56:10591068. 13. Hall W, Solowij N. Adverse effects of cannabis. Lancet. 1998;352:16111616. 14. British Medical Association. Therapeutic Uses of Cannabis. London: Harwood Academic Publishers; 1997. 15. Sridhar KS, Raub WA, Weatherby NL. Possible role of marijuana smoking as a carcinogen in the development of lung cancer at an early age. J Psychoactive Drugs. 1994;26:285288. 16. Benson M, Bentley AM. Lung disease induced by drug addiction. Thorax. 1995; 50:11251127. 17. Lawson TM, Rees A. Stroke and transient ischemic attacks in association with substance abuse in a young man. Postgrad Med. 1996;72:692693. 18. Flisberg P, Paech MJ, Shah T, et al. Induction dose of propofol in patients using cannabis. Eur J Anaesthesiol. 2009;26:192195. 19. Pertwee RG. Neuropharmacology and therapeutic potential of cannabinoids. Addict Biol. 2000;5:3746. 20. Smith WDA. Under the Inuence: MacMillan Pub Ltd Old Wokiing. 1982:20. 21. Priestley J. Observations on different kinds of air. In: Philosophical Transactions. Royal Society of London; 1772;62:210224. 22. Davy H. Researches, Chemical and Philosophical: Chiey Concerning Nitrous Oxide or Dephlogisticated Nitrous Air, and its Respiration. London: Biggs and Cottle for J Johnson; 1800:548549. 23. Wright AJ. Davu comes to America: Woodhouse, Barton, and the nitrous oxide crossing. J Clin Anesth. 1995;7:347355. 24. Wells A. A History of the Discovery of the Application of Nitrous Oxide Gas, Ether and Other Vapors to Surgical Operations. Hartford CT: J Gaylord Wells; 1847. 25. Blanton A. Nitrous oxide abuse: dentistrys unique addiction. J Tenn Dent Assoc. 2006;86:3031. 26. Tymoczko D. The Nitrous Oxide Philosopher Atlantic Monthly. The Atlantic Monthly; 1996;277:5:93101. 27. Gillman MA. Nitrous Oxide, an opioid addictive agent. Review of the evidence. Am J Med. 1986;81:97102. 28. Dzoljic MR, Haffmans J, Ruprehy J, et al. Decrease of beta endorphin in the brain of rats following nitrous oxide withdrawal. Drug Metabol Drug Interact. 1991;9: 139148.
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29. Yagiela JA. Health Hazards and nitrous oxide: a time for reappraisal. Anesth Prog. 1991;38:111. 30. Lin CY, Guo WY, Chen JT, et al. Neurotoxicity of nitrous oxide: multimodal evoked potentials in an abuser. Clin Toxicol (Phila). 2007;45:6771. 31. Wu MS, Hsu YD, Lin JC, et al. Spinal myoclonus in subacute combined degeneration caused by nitrous oxide intoxication. Acta Neurol. 2007;16:102105. 32. Cartner M, Sinnott M, Silburn P. Paralysis caused by nagging. Med J Aust. 2007; 187:366367. 33. Waters MF, Kang GA, Mazziotta JC, et al. Nitrous oxide inhalation as a cause of cervical myelopathy. Acta Neurol Scand. 2005;12:270272. 34. Butzkueven H, King JO. Nitrous oxide myelopathy in an abuser of whipped cream bulbs. J Clin Neurosci. 2000;7:7375. 35. Garbaz L, Mispelaere D, Boulemy M. Pneumothorax following recreational inhalation of nitrous oxide. Rev Mal Presp. 2007;24:622624. 36. Hwang JC, Himel HN, Edlich RF. Frostbite of the face after recreational misuse of nitrous oxide. Burns. 1996;22:152153. 37. Kong JT, Schmiesing C. Concealed mothball abuse prior to anesthesia: mothballs, inhalants, and their management. Acta Anaesthesiol Scand. 2005;49:113116. 38. Kurtzman TL, Otsuka KN, Wahl RA. Inhalant abuse by adolescents. J Adolesc Health. 2001;28:170180. 39. Perron BE, Howard MO, Vaughn MG, et al. Inhalant withdrawal as a clinically signicant feature of inhalant dependence disorder. Med Hypotheses. 2009;73: 935937. 40. Keriotis AA, Upadhyaya HP. Inhalant dependence and withdrawal symptoms. J Am Acad Child Adolesc Psychiatry. 2000;39:679680. 41. Shen YC. Treatment of inhalant dependence with lamotrigine. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:769771. 42. Maclver BM. Abused inhalants enhance GABA-mediated synaptic inhibition. Neuropsychopharmacology. 2009;34:22962304. 43. Lopreato GF, Phelan R, Borghese CM, et al. Inhaled drugs of abuse enhance serotonin-3 receptor function. Drug Alcohol Depend. 2003;70:1115. 44. Bieda MC, Su H, MacIver MB. Anesthetics discriminate between tonic and phasic gamma-aminobutyric acid receptors on hippocampal CA1 neurons. Anesth Analg. 2009;108:484490. 45. Sicinski M, Kadam U. Monitoring of the anesthetic volatile agent may be impaired in hydrocarbon abusers. Anesthesia. 2002;57:510511. 46. Bass M. Sudden snifng death. JAMA. 1970;212:20752079. 47. Perron BE, Howard MO. Adolescent inhalant use, abuse and dependence. Addiction. 2009;104:11851192. 48. Broussard LA. The role of the laboratory in detecting inhalant abuse. Clin Lab Sci. 2000;13:205209.

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