Topical Anesthetics, Cocaine
Author: John J Simmer, MD,, Assistant Professor of Surgery, Uniformed Services University of the Health Sciences; Assistant Chief of Otolaryngology-Head and Neck Surgery Service, Madigan Army Medical Center
Coauthor(s): Don R Revis Jr, MD, Consulting Staff, Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Florida College of Medicine; Michael Brent Seagle, MD, Associate Professor, Division of Plastic Surgery, University of Florida College of Medicine; Consulting Staff, Florida Surgical Center
Contributor Information and Disclosures
Updated: Jul 31, 2008
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Introduction and History
Cocaine is an alkaloid derived from the leaves of the coca plant (Erythroxylon coca). It is the only naturally occurring local anesthetic in medical use today. Indigenous to the Andes Mountains, West Indies, and Java, its use was touted over the centuries as a method of reducing fatigue and promoting a sense of well-being.
Cocaine was introduced into Europe in the 1800s. Sigmund Freud used cocaine on his patients and became addicted through self-experimentation. Niemann first isolated and purified cocaine in 1859. In the latter half of the 1800s, widespread interest in cocaine developed among the medical community, and, during this period, many of the pharmacologic actions and adverse effects were elucidated.
In the 1880s, Koller introduced cocaine into the practice of ophthalmology and Hall introduced it to dentistry.
Chemical structure of cocaine.
[ CLOSE WINDOW ]Chemical structure of cocaine.
Cocaine was widely available at the outset of the 20th century, and Coca-Cola contained approximately 4.5 mg/180 mL. With widespread use, the problems of abuse and addiction became apparent, and the Harrison Narcotics Act of 1914 essentially banned distribution of cocaine in the United States, except by prescription.
Today, cocaine continues to be used for recreational and medical purposes. Medical use is confined primarily to operative procedures of the nose and throat and treatment for dermal lacerations in children.
Mechanism of Action
Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. When a nerve loses its ability to propagate an impulse, the individual loses sensation in the area supplied by the nerve.
Cocaine also has a profound effect on the CNS. Cocaine blocks reuptake of dopamine in the midbrain region responsible for reward mediation. This leads to increased stimulation and a sense of euphoria and arousal. As the cocaine level decreases, so does the dopamine level in this region, resulting in depression and a craving for the drug.
Cocaine also blocks the reuptake of norepinephrine in the sympathetic portion of the autonomic nervous system and may stimulate the release of catecholamines from the adrenal gland, resulting in increased stimulation of the sympathetic nervous system. This results in the characteristic tachycardia, hypertension, diaphoresis, mydriasis, and tremors associated with cocaine use.
Cocaine is the only local anesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system.
Absorption and Metabolism
Cocaine is absorbed rapidly through mucous membranes, and peak plasma levels (ie, 120-474 ng/mL) are reached within 15-60 minutes. Half-life in serum is 30-90 minutes.
Cocaine is metabolized in several ways. Hydrolysis by plasma pseudocholinesterases accomplishes most cocaine degradation to benzoylecgonine, cocaethylene, and several other metabolites.
Oxidative metabolism in the liver produces norcocaine, a toxic substance capable of causing severe hepatic damage. Up to 20% of absorbed cocaine is excreted in the urine unmetabolized.
Cocaine is detectable in the nasal mucosa for 3 hours following application. Serum and urine levels are measurable for approximately 6 hours following application.
Clinical Uses
Cocaine is used for topical anesthesia and vasoconstriction for surgery of the nose, throat, and oral cavity. Cocaine provides rapid and profound anesthesia in conjunction with vasoconstriction and decongestion of swollen mucosa.
Cocaine hydrochloride is available commercially in the United States as flakes, crystals, 135-mg tablets, and solutions of various concentrations. The flakes and crystals are intended for application via moistened cotton swabs. The tablets are to be used in preparation of a topical solution. The premade topical solutions are available in strengths ranging from 2-10%, with a 4% solution most frequently referenced.
The safe maximum dosage is reported to be 200 mg or 2-3 mg/kg, but this is based on anecdotal observations rather than controlled studies. Even 200 mg can cause adverse reactions if rapidly absorbed. Spraying or painting cocaine on the intended surgery site causes more rapid absorption than application by patch or pledget. Clinical studies have shown that only approximately one third of a cocaine solution placed on pledgets is absorbed via the nasal mucosa, with serum levels continuing to rise for 5 minutes after removal. This provides an added margin of safety for the surgeon.
When epinephrine is added to the solution to promote further vasoconstriction, systemic absorption decreases; however, according to published series, the decrease is inconsistent. Late absorption of cocaine has also been reported when cocaine is administered with epinephrine. Therefore, the use of epinephrine cannot be assumed to protect from systemic cocaine absorption. The addition of epinephrine has also been reported to enhance the sympathomimetic action of cocaine, causing hypertension and tachyarrhythmias.
To use cocaine in the nasal cavity, cotton pledgets are soaked in the cocaine solution. After being wrung out, the pledgets are introduced into the operative field with bayonet forceps. Pay particular attention to placing the pledgets in contact with the mucosal surface.
After the pledgets have been in place for at least 10-15 minutes, they may be removed from the side to be approached first. Infiltration of submucosal lidocaine with epinephrine may then be performed. This is best performed with a small syringe and 25-gauge or smaller needle. Proper placement creates blanching of the mucosa. Rarely is more than 1.5 mL required for each side. After allowing several minutes for the injected solution to take effect, inspect the mucosa for the anticipated vasoconstriction. If the patient reports pain at this time or further along in the operative course, pledgets may be loosely reapplied.
Cocaine has also been used as a topical spray for analgesia during transnasal fiberoptic laryngoscopy and awake nasotracheal intubation. Superiority over topical analgesics that do not contain cocaine has not been established.
Another more recently developed use of cocaine is in combination with tetracaine and adrenaline (TAC), composed of 0.5% tetracaine, epinephrine 1:200,000, and 11.8% cocaine. This combination has been used in the pediatric population for suturing lacerations less than 10 cm long in the emergency department. It has been found to be most effective in the head, neck, and scalp; less effective in the trunk; and ineffective in the extremities.
A few drops of the solution may be placed directly on the wound, or, preferably, a moistened cotton ball soaked in the solution may be applied to the wound. Constant gentle pressure is then applied to the cotton balls for 10-20 minutes. After testing the adequacy of anesthesia, the wound may be irrigated, cleansed, and sutured. Inadequacy of anesthesia is remedied by injection of local anesthetic. It should not be used on mucous membranes, large abrasions, or burn areas due to the risk of rapid absorption and systemic toxicity.
Monitor the patient with pulse oximetry and telemetry during use of TAC. In addition, observe the patient for any signs or symptoms of systemic toxicity. Following application and suturing, observe the patient for an additional 60 minutes to ensure that no untoward effects of cocaine absorption occur.
The benefits of TAC include ease of application, patient comfort during application, and avoidance of wound distortion from the injection of local anesthetic solution. This technique has been proven safe and effective in numerous published studies and has gained wide popularity among emergency departments. More recent studies suggest that alternative cocaine-free topical anesthetics are equally effective, with the benefit of decreased risk and cost.
Toxicity and Adverse Reactions
Although adverse reactions to cocaine seldom occur in the medical field, those that do may be rapid, unexpected, and severe. Other good alternatives for anesthesia are available, and many surgeons have ceased using cocaine because of its unpredictable effects and the risk of having such a highly addictive drug in the office.
Cocaine toxicity may have profound adrenergic effects on the CNS, cardiovascular system, and respiratory system. Sympathetic stimulation of the cardiovascular system may lead to hypertension, tachycardia, ventricular fibrillation, and cardiac arrest. Other serious complications include direct cardiotoxicity, angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, pulmonary edema, hepatotoxicity, intestinal ischemia, seizures, and CNS depression.
Cocaine readily passes into breast milk and across the placenta, an important consideration in patients who are pregnant or nursing. Stillbirth, preterm labor, and abruptio placentae may occur. Intrauterine growth is also restricted. These often-profound effects on the fetus may continue after birth. Developmental delay is common in children born to mothers with cocaine in their system.
Management of Toxicity
The cornerstone of treatment for cocaine toxicity is early recognition and action. The treating physician must curtail the operative procedure and remove any remaining pledgets. Immediately activate advanced cardiac life support protocols, including intubation and defibrillation if indicated.
Above all, seek help immediately. In a hospital setting, assistance is readily available. In the office surgery setting, call emergency services (ie, dial 911 in the United States) immediately. The surgeon must direct resuscitation until assistance arrives. This requires that any surgeon using cocaine in the office be familiar with advanced cardiac life support protocols and have the proper equipment on hand should an emergency situation arise.
Cocaine toxicity has no known antidote. Aggressive resuscitation is the only treatment. In addition to intubation and defibrillation, administering drugs such as propranolol, nitrates, calcium channel blockers, and alpha-adrenergic blockers may be necessary in an attempt to improve coronary blood flow and restore normal sinus rhythm. Control seizure activity with diazepam (Valium), and aggressively treat hyperthermia with cooling blankets.
Contoversies
Controversy still exists over the use of cocaine in otolaryngology. Criticisms include the risks, cost, problems with storage and dispensing, or combinations of these problems. Much of the literature references a survey done in 1977 regarding cocaine use by otolaryngologists. This survey preceded the epidemic of recreational cocaine use and the first reported case of cocaine-induced myocardial infarction. A more recent survey in 2004 showed that physicians in practice less than 10 years were less likely to have used cocaine than those in practice more than 10 years.1 Compared with the 1977 survey, fewer physicians reported ever using cocaine in their practice, and a greater number of adverse reactions were reported.
Recent studies suggest that safer alternatives for topical anesthesia with equal effectiveness are available. The treating physician must be aware of potential interactions between cocaine and other medications, and to consider an alternative if concern about the cardiac status of the patient exists.
Multimedia
(Enlarge Image) Media file 1: Chemical structure of cocaine.
[ CLOSE WINDOW ]Chemical structure of cocaine.
Keywords
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