Oral Conscious Sedation

Enteral conscious sedation (ECS), also called oral conscious sedation , has a lot of appeal on both sides of the dental chair. For the large population afraid to step foot in the dental office, swallowing a pill may be the difference between clean healthy teeth and painful oral health problems. For trained dentists, ECS can be feasible to administer, doesn't usually entail the complications compared to IV and other types of sedation, and often promotes goodwill among apprehensive patience who are ware that there is an option.

Enteral conscious sedation is primarily used to curb anxiety and fear in a patient without rendering them unconscious. Several polls and surveys suggest that fear of the dentist remains pervasive despite advancements in pain management, improved patient comfort techniques and various public-awareness campaigns. Ironically, sedation via a needle is a chief concern of more than half of all patients afraid of dental visits. According to a clinical article in the February 1998 issue of the Journal of the American Dental Association , one survey found that "25 percent of adults expressed a fear of injections, with one in 20 respondents indicating that they avoided, canceled or did not appear for dental appointments because of fear."

Prior to the 1960s, alcohol and barbiturates were used to relax patients. Once benzodiazepines were FDA approved and available on the market, they became the drugs of choice for dentists. Triazolam is the benzodiazepine most commonly used by dentists because of its rapid onset, reported high margin of safety, and the availability of the antagonist flumazenil. Triazolam's popularity with dentists also stems from the drug's short half-life and duration.

The Procedure

The patient comes to the office one hour before we wish to start their dental procedure. We determine the appropriate dose and have them take the triazolam at that time. Many authors have reported on the appropriate dosage for sleep enhancement. Suggested dosages range from .125 mg. to .5 mg.

We usually administer a dose that is lower than we expect will be adequate the first time we treat a patient. An assistant or doctor stays in the operatory with them for the next hour taking vital signs, blood pressure, pulse, and respiration every 15 minutes with instructions to alert the doctor if there is any change. The assistant talks with them to assure that they remain awake. We check to see if there is any sign of sedation at thirty minutes. If there is no sedation evident, we may administer one half the original dose. If even slight sedation is noted at that time, we normally will have adequate sedation for the procedure. (Many patients will be disappointed at the end of the forty minutes by the relative lack of sedation. They are assured that this is normal and they will be adequately sedated by the time we start.) Studies have found that about 75% of patients have amnesia from this point which lasts for 2-3 hours. All patients have had some amnesia of the appointment.

The dental procedure is started at 45 minutes to 1 hour after administration of the drug. We continue to monitor vital signs and talk to the patient to be sure they are awake.

Once the appointment is complete we keep the patient in the dental chair until they are able to walk and we determine they are able to safely leave the office. Post operative instructions, the same as were given to the patient in the pre-appointment interview (see above), are reviewed with the adult who is going to take the patient home and watch over them the rest of the day. In addition, our On-Call telephone number is given to this adult who is encouraged to call if they have any questions or problems. Finally, an assistant usually accompanies the patient out of the office supporting the patient so there is no chance of a fall.

It should be noted that the second appointment will normally be easier and more routine than the first. It is usually unnecessary to use a higher dose if the first dose was adequate. Also, as this is a class IV drug, it is necessary to keep careful accounting records on its use.

Our In-Office Protocol

It should be stressed that we do not want a patient who is asleep. If a patient sleeps they are over-sedated and should be kept awake by verbal commands. We do not worry if the patient is disappointed by their level of sedation because the amnesia that is common to this technique will allow them to forget most if not all of the appointment. It should be emphasized with children that they may still cry during the appointment. If they are controlled enough to allow dentistry to be safely done, they are adequately relaxed and crying, although distracting to the practitioner, is an indication of adequate ventilation.

Because dental sedation is a relatively new treatment parameter, unreported use of triazolam, we should remain extremely cautious. Any medical problems known to the patient, must be promptly reported to the dental team and the doctor, however slight.

At a pre-appointment interview, we review medical history to determine that there are no contraindications. At that time, a team member will usually review with the patient the following points:

They are to have no alcohol or other sedatives for twenty-four hours before the appointment. Any medications, including over-the-counter items should be reported.

There should be no chance that they are pregnant.

They have none of the other contraindications.

They will have an adult take them home after the appointment and remain with them and be able to continually monitor them the remainder of the day and that evening.

As with all sedatives, they cannot drive, operate machinery or undertake any activity that could be deemed hazardous. This includes such activities as walking unaided, climbing stairs, preparing food, etc.

They should not undertake positions of responsibility, care of children, job related decisions, etc.

They should not make important decisions, legal or monetary, etc., for the rest of the day.

They should not have ANY alcohol or other sedatives for twenty-four hours after the appointment.

 

A BRIEF DISCUSSION OF ORAL SEDATION AND ROUTES OF DRUG ADMINISTRATION

In attempting to create a state of tranquility, we must get a certain concentration of agent to the appropriate location in the central nervous system (CNS). The effect can be altered by varying the agent. Some agents are more therapeutic than others. In gaining access to the appropriate areas of the CNS, a variety of routes of administration can be used.

Ultimately, this access depends on introducing the drug into the circulation of arterial blood serving the brain. Since we are treating apprehensive patients, it is important to gain this access with as little discomfort as possible. Through inhalation, gaseous agents gain access via the lungs; liquid agents may be injected into the venous circulation, sprayed on nasal mucosa, absorbed sublingually, and injected under the skin into underlying muscle or swallowed and absorbed from the stomach and small intestine. Some agents have been administered rectally.

When considering routes, we should consider patient comfort, time to achieve effect, control of the effect, ease of administration, the skill needed for administration of the drug, necessary equipment for administration and monitoring of the patient. Unfortunately, we must also consider medical-legal questions of insurance and regulation by governmental organizations.

In general, the faster the drug reaches the CNS and has an effect the better control we have of the sedation. By titrating for effect, we can give just that amount of drug that is necessary to control apprehension. Both intravenous and inhalation agents can be readily controlled in this manner. Other routes of administration require administering an appropriate dose and waiting up to an hour to see the desired effect. It is obvious that it is impractical to titrate when we must wait for an hour to see the effect. These routes require very specific dosages usually associated with body size. They require conservative dosages as hypersensitivity to a medication will not be obvious until it is much too late to adjust the dosage. It is imperative that a drug with a very wide range of safety be used when these slower routes of uptake are utilized. Ideally, we will have reversal agents that can deactivate the drug in the case of overdose when using these routes.

We in dentistry have used and continue to use a variety of agents and combinations of agents. Multiple agents often complicate the treatment as each has side effects which may be addictive. They all are CNS depressants and some have unwanted depressing effects on respiratory and the cardiovascular systems. The combination of all these effects can lead to problems that are hard to predict and even more difficult to control. However, if only one agent is used, the side effects are often more predictable.

In general terms, it is easier (safer) to use a single agent as we then only have one set of side effects to contend with. This, of course, assumes a single agent will provide the needed effect at a concentration where few side effects are present. When Dione looked at combinations used by 264 dentists he found 82 distinct combinations. "The scientific basis for the use of such a diverse group of agents and combinations is unclear."

Inhalation sedation

The inhalation route of administration offers a major advantage when we consider an overdose. By removing the source of the drug (having the patient breathe room air or 100% oxygen), they will excrete most inhalation agents via the lungs, thus reversing the overdose. A practitioner must assure that the patient's respiratory system is functioning normally and that their tidal volume is adequate to provide the oxygen they need and remove their carbon dioxide both for their safety and to remove the inhalation agent. It should be remembered that all agents depress the respiratory system to some extent and it is important to have monitors that assure that an adequate exchange is taking place. It is necessary that the practitioner be skilled in assisting respiration should significant depression take place.

Intravenous sedation

With the regulations that are now in place in many states, it is nearly impossible to use intravenous sedation. Many states require a 60 hour course in addition to any training that was received in dental school. These courses have not been taught for a number of years and do not seem to be coming back. The cost of malpractice insurance to do intravenous sedation is another problem. If the added cost of malpractice insurance is passed on to the patient, it can increase the cost of each appointment $100 to $200.

Intravenous sedation has several advantages to the oral route of administering medication. When giving a drug IV, one slowly titrates the concentration of a drug to the level of sedation desired. For most drugs, these effects began to diminish in a short period of time - first, due to redistribution to other tissues (primarily fat stores) and then more slowly as the drug is metabolized into inactive forms (in some cases less active forms) or eliminated in the urine or feces.

Oral Sedation

Several factors come to light when we consider oral sedatives. The time from ingestion to sedation becomes very important. For any effect to take place, the drug must be absorbed into the blood stream and delivered to the site of action, usually thought to be in the central nervous system, in sufficient quantities to be effective. Some drugs can be absorbed sublingually, others must be swallowed and absorbed from either the stomach or small intestine. Depending on the time necessary for absorption, it may be necessary to have the patient take the drug at home before coming to the office. However, I prefer to administer the drug in the office because then I know how much was taken, when it was taken, and by whom it was taken. Also, I don't have to worry about the patient trying to drive to the appointment as the drug starts to take effect. Last but not least, should there be a reaction to the drug, the patient is in the office where aid can be administered.

We need a predictable means of determining dosage. Because it will take 45 minutes to one (1) hour to get the desired sedation, we can not easily titrate or alter the dose if a patient is not adequately sedated. Because of the length of time necessary to get sedation, we can not depend on redistribution of the drug to counter its effect. With some intravenous drugs you can give a dose necessary for sedation and within a few minutes have the patient nearly back to normal because the drug concentration in the blood stream has been reduced as the drug is redistributed to other tissues of the body.

DRUG OPTIONS

Historically, many drugs and routes of administration have been used to control apprehension in the dental offices of general practitioners. As stated earlier, insurance companies, state regulatory bodies and other factors have all but eliminated intravenous sedation from the armamentarium of general dentists. If we trace the history of the other methods of sedation, however, we will see that all is not lost for the phobic patient.

Nitrous oxide

Nitrous oxide has an interesting history. Originally it was used as an attraction at public science shows. It was at such a program that a dentist, Horris Wells, saw a participant in a nitrous frolic bark a shin, causing a dramatic wound ... with no pain. He took this knowledge to his office and began offering painless dentistry using nitrous oxide as a general anesthetic. This was a major breakthrough when you consider that any dentistry or surgery up until that time was accomplished with no pain control and depended to a great extent on the speed of the surgeon if the patient was to survive the shock of the procedure. Thus, surgeons became known for their speed. But in the quest for speed, accuracy sometimes suffered and more than one assistant lost a digit or two to the surgeon's knife when holding a limb for amputation. Not surprisingly, the fastest surgeons sometimes had a difficult time finding willing assistants.

Ever since Wells' first use of Nitrous oxide in a medical environment, it has been used as a general anesthetic and, more recently, as a sedative on the conscious patient. Its history as a general anesthetic has brought dentistry some criticism. Nitrous oxide is such a weak anesthetic agent, at one atmosphere of pressure, that 80% nitrous oxide is usually considered to be the minimum concentration that will achieve unconsciousness. Even at this concentration, however, it is not possible to render some patients unconscious and if we go to a higher concentration, we begin to encroach on the 21% O2 found in the atmosphere and expose our patients to hypoxia.

The standard of years gone by was to watch the patient's color. When they began to show a blue tinge of cyanosis, the procedure was started. I like to state, tongue in cheek, that dentists hoped the pain of the extraction would restart the heart. Actually, many general anesthetics were done by this technique with an amazing safety record, which may be more testimony to a patient's desire to live than to the safety of the procedure. Today, hypoxic anesthesia would be severely criticized, and rightly so.

Because it is absorbed and removed from the blood stream via the lungs essentially unchanged, nitrous oxide is a very safe sedative. But its major disadvantage - its relative weakness - is also its major advantage. In other words, although sedation with nitrous oxide is not adequate for our most phobic patients, because it is such a weak anesthetic agent there is little risk of sedation rendering the patient unconscious, that is, in a state of general anesthesia with its depressed reflexes and other hazards.

Our primary concern in anesthesia is the loss of swallowing and laryngeal reflexes that can lead to regurgitation of stomach contents and aspiration of the low pH matter into the lungs. So long as a 50% concentration of nitrous oxide is not exceeded, there is little chance of general anesthesia or other more minor complications occurring. The complications that may arise are not serious ones. Occasional vomiting may be seen. But since our patients are always conscious, this is not serious as protective laryngeal reflexes are present; however, the patient is definitely uncomfortable and vomiting certainly can be messy.

The euphoria of nitrous may remind some patients of periods when they were sedated for other reasons, which may be traumatic if the occasion was due to a personal tragedy. Patients will occasionally hallucinate; this again can be uncomfortable for them.

Treatment consists of removing the source of nitrous oxide, and reassuring the patient, typically by telling them they are all right and will return to normal in a few minutes. I find it helpful to continually assure the patient until the hallucination is over. Use their first name, and remind them they are in the dental office, that they should relax and will be back to normal in a few minutes.

Another potential problem deserves mention - that of sexual aberrations. A certain number of female patients will experience sexual feelings while on nitrous oxide. This can happen at relatively low concentrations. Some patients describe the sensation of sexual orgasm. It is not all that easy to identify when this is taking place and what is happening. However, if it looks like a duck, walks like a duck and quacks like a duck, the chances are we are observing a duck. This may, in fact, be the ultimate distraction to dental treatment. Fortunately, it is very rare. For this reason, a dentist should be closely accompanied by a female dental assistant when treating female patients with nitrous oxide. This phenomenon has never been documented in male patients.

A potentially more serious problem can arise if we treat chronic obstructive pulmonary disease (COPD) patients with nitrous oxide. These patients do not exchange gasses well in their lungs. Rather than having many small alveoli with the resulting large surface area to exchange gasses with the blood stream, they have fewer large alveoli, often with scarring which thickens the alveolar wall. Carbon dioxide does not diffuse out of the blood stream nor does oxygen enter the blood stream as quickly as is seen in the normal patient. Carbon dioxide levels increase in the blood stream, causing a decrease in pH because of the increased concentration of hydrogen ions. An increase in concentration of bicarbonate ions tends to buffer the effect of this lowered pH, rendering this stimulate, low pH, less effective. These patients depend on low oxygen levels as a primary stimulant to respiration. If we give such a patient nitrous oxide, it tends to depress this secondary system. The relatively high concentrations of oxygen associated with nitrous mixtures, usually greater than 50% oxygen, render this secondary system ineffective and respiration may cease. A further complicating factor has to do with nitrous oxide's tendency to diffuse into closed spaces. The lungs of COPD patients often have large, gas-filled sacks or blebs. If nitrous oxide diffuses into these spaces, it can cause them to enlarge, possibly to the point of rupture. Should a person be overdosed with nitrous oxide, it is a simple matter of removing the source of the gas and, provided the patient is breathing, they will eliminate the excessive concentration of nitrous oxide.

Probably the greatest chance of complications when using nitrous oxide can be traced to the gasses being switched. I know of 25 to 30 cases where this has occurred. It can happen in several ways: Plumbers may install nitrous oxide and oxygen lines reversed; machines have been reversed by manufacturers; small tanks depend on a safety pin index system. This system has been compromised by having pins displaced from the tank yolk and by practitioners allowing more than one washer to be placed between the tank and the yolk, rendering the pins ineffective.

It has been the standard to oxygenate the patient for 5 minutes after each nitrous oxide administration to avoid diffusion hypoxia. If oxygenation is continued when gasses are reversed, the patient would be receiving no oxygen and the lack of oxygen will eventually lead to death. In a study we did of over 100 patients, we saw no evidence of diffusion hypoxia. For the healthy patient who uses only nitrous oxide for sedation, there is no reason to oxygenate patients after nitrous oxide. It should be stressed that nitrous oxide is a very safe sedative for almost all patients.

Alcohol

Alcohol has been used by some patients for years to help with their dental treatments. It is not unusual for a patient to self medicate themselves with a bit of liquid reinforcement before coming to an appointment. It is important when considering the use of other drugs for apprehension control that patients be warned against using any other substance that is a central nervous system depressant. The combination of benzodiazepines and alcohol has lead to very serious respiratory depression. The regular or occasional use of any medications or recreational drugs should be promptly reported to the doctor BEFORE sedation is scheduled or initiated.

Chloral hydrate

This drug has been a favorite, particularly for children. It can be very unpredictable. Evidence is now emerging that indicates it may not be as safe as we all believed. Chloral hydrate is a halogenated derivative of acetaldehyde. Its sedative action comes from its metabolite, trichloroethanol. The peak activity occurs in the plasma within 20 to 60 minutes after oral administration. Its half life is 4 - 12 hours. It acts primarily on the CNS and has little effect on the respiratory and cardiovascular systems of healthy patients. However, a pulse oximeter is advised to monitor as you can get respiratory depression and still have a conscious patient.

Laryngospasm has been reported with 250 mg. Life threatening hypotension and respiratory arrest have been reported in doses exceeding 85 mg/kg. Below 50 mg/kg. there have been few reports of problems. Higher doses tend to induce vomiting, however, thereby lowering the amount absorbed. In one case, although the patient vomited repeatedly starting 5 minutes after an overdose had been administered, they eventually became semi-conscious and suffered cardiac arrest.

In higher doses, chloral hydrate tends to become a cardiac irritant. There have been several reported cases of overdose leading to hypotension. When the hypotension was treated with chatecholamines or agents that released chatecholamines, both patients experienced cardiac arrest; one survived, the other did not. Any other CNS depressant will enhance the sedation-depression of chloral hydrate, including nitrous oxide and narcotics.

Barbiturates

Barbiturates were the standard anti-anxiety agent for both medical and dental patients for many years. This was true even though pharmacologists never claimed that barbiturates dealt specifically with the brain mechanisms responsible for anxiety; they simply make a patient drowsy, and sleepy patients tend to be less apprehensive. In larger doses, barbiturates have the potential to render patients asleep. It is in this way that the short and ultrashort acting barbiturates were used as induction agents for general anesthesia and for very brief general anesthetics.

The ratio of the dose necessary for sleep and the dose that will end in death - the therapeutic index - is usually stated to be a factor of 2 as compared to diazepam with a ratio of 20. Unfortunately, these drugs in higher doses tend to be potent cardiac and respiratory depressants. Because of their addictive nature, they were not administered for long-term anxiety control.

Benzodiazepines

The first step toward developing drugs that act selectively on anxiety mechanisms came about somewhat by chance. In the 1940's a Czechoslovakian pharmacologist, Frank Berger, was attempting to develop synthetic antibacterial agents that would kill microorganisms resistant to penicillin. One group of chemicals, when injected into mice, caused them to become temporarily paralyzed because of a massive relaxation of the muscles in their limbs although they were fully conscious. In his first publication on the effects, Berger referred to this effect as "tranquilization." He sought derivatives of this original drug, mephenesin, that might be better at controlling anxiety. He found a derivative, Meprobamate, did just that. Meprobamate was introduced to the public in 1955. Although less effective than hoped, it served to introduce the concept of a drug agent capable of dealing selectively with anxiety. The race was on to find such a drug. It is interesting that in later analysis it was shown that Meprobamate was only a sedative; it did not selectively alleviate apprehension. It had, however, stimulated a search for such specific anti-anxiety drugs. As no one knew the mechanism involved, many drugs were tried on an almost random basis to see if any had the desired effect.

Twenty years earlier, in the 1930's, Leo Sternbach had begun a research career in pure chemistry at the University of Kracow , Poland . On the basis of his early research he began a search of a group of chemicals he referred to as quinazolines, but after two years he had failed to show any of the desired effects in this group of chemicals.

A year and half later, while cleaning up his lab, Sternbach found one of the last quinazoline series he had not tested. He gave it to Lowell Randall, Roache's head of pharmacology. This drug turned out to be the most active agent of the group and became known as Librium. Sternbach discovered it was not a quinazoline class, but in the final stages of synthesis had been transformed into a completely different chemical, a new class known as benzodiazepines. From this early success came a number of librium derivatives, the most effective of these, diazepam.

Librium and diazepam do relieve anxiety. They produce some drowsiness and, unfortunately, are somewhat addicting. Tolerance develops with continued use and withdrawal occurs when the drug is stopped. However, the extent of tolerance and withdrawal are less than what is seen with barbiturates.

The most clear-cut advantage of the single agent, benzodiazepine sedation is the fact that overdoses are rarely lethal. In the case of barbiturates, on the other hand, the lethal dose is only a few times greater than the dose necessary to cause sleep. It is not uncommon when testing benzodiazepine drugs on mice to give doses a thousand times greater than is necessary to cause muscle relaxation and behavioral effects and still have the mice, cats, rats, and monkeys all refuse to die. One should not become overconfident, however, as when added to alcohol or barbiturates, death can result.

To deactivate most oral sedatives we generally must wait for the drug to be excreted or metabolized. In the case of diazepam it is metabolized in liver to another sedative, oxipam, that is available as a long term sedative on its own. Triazolam, along with midazolam, has the shortest half-life of the benzodiazepine drugs; both are in the 1 to 2 hour range. Midazolam is normally considered to be an intravenous drug although it is beginning to be used orally (mixed in cola drinks) and as a nasal spray. Unfortunately, it has been shown to have a noticeable respiratory depressant effect in higher doses. Triazolam has rapid uptake (about 1 hour to maximum effect), and may be given sublingually for an even faster effect, although it is felt that much of the effect still comes from the drug that is swallowed. It has a half life that is about 1 - 2 hours and very little, if any, cardiac or respiratory depressant effect.

It is this very short half life that makes Triazolam a favorite of mine. The high incidence of retrograde amnesia on conscious patients further endears it to the dental practitioner. Patients do not have to be asleep for their dental treatments if they can be relaxed enough for us to do the required procedures and not have any memory of the procedure. Triazolam's relative lack of respiratory and cardiovascular sedation is important for safety. Safety is dependant on the ratio of the L/D 50 dose (that dose usually fatal to rats) and the concentration that provides sedation (to rats). It is our hope that this ratio is constant for humans. Evidence from self-inflicted overdose emergencies tends to indicate a similar ratio. The self-inflicted overdose patient may sleep for several days but they usually survive if they have not mixed the benzodiazepines with other drugs such as alcohol or barbiturates. The higher the difference between these numbers, the safer the drug. For healthy patients it has been estimated that a lethal oral dose - in absence of any other CNS depressant - must be very large and could be impossible to administer orally. -

RESPIRATION

In all cases of dental sedation patients should remain awake. If the patient tends to fall asleep, they will usually be awakened. It should be noted that several studies have shown that watching the chest and/or reservoir bag move is not adequate to assure an adequate minute volume. Skin color has been relied on in the past as a way of assuring adequate tissue profusion. However, the arterial oxygen level can be dangerously low before we see the blue tinge of cyanosis. Anyway, cyanosis is no longer considered to be an adequate monitor of arterial oxygen levels. In this case a pulse oximeter and/or capnograph is invaluable in assessing the adequacy of ventilation.

To properly appreciate the importance of monitoring respiration as well as the advantages of the benzodiazepine drugs, it would be wise to review the physiological basis of ventilation. It should be used as the minimal level of knowledge one can possess and still have some appreciation of what we are doing with the drugs we use.

Physiological basis of ventilation

Ventilation is the movement or circulation of air through the respiratory tract and is the principal component of respiration influenced by depressant drugs. We can control our ventilation by conscious effort, however, our bodies have an exquisite system of sensors, reflexes, and feedback loops to control ventilation involuntarily. The involuntary control originates in the chemosensitive area of the respiratory center located in the ventral portion of the medulla. Metabolic processes of our body produce carbon dioxide (CO2) which is carried dissolved in our blood. When CO2 combines with the water in our plasma, it forms carbonic acid which disassociates into hydrogen ions and bicarbonate ions. The negative logarithm of our hydrogen ion concentration determines the pH of our blood. It is this pH which stimulates the chemosensitive region of the respiratory center.

Carotid and Aortic Bodies

The carotid and aortic bodies are closely associated with major arteries of the neck. These harbor other chemosensitive formations sensitive to the low arterial oxygen levels of the blood. Their greatest influence occurs at tension below 60 torr. Because normal levels are well above this value 95-99 torr, these serve as a back-up to the central CO2 sensitive chemoreceptors. Exceptions occur when the central chemosensitive area is depressed by sedative drugs or is tolerant to elevated CO2 tensions that accompany chronic obstructive pulmonary disease (COPD). Ascending impulses from this area travel via the IX and X cranial nerves to the respiratory center.

Respiratory Center Once the respiratory center is stimulated, impulses travel a short distance to the more dorsally located inspiratory area. This area produces descending neural impulses that lead to the inspiratory musculature causing a contraction of these muscles and inflation of the lung. Once the lung is inflated, stretch receptors ascend to depress the inspiratory area, allowing the inspiratory musculature to relax. This in turn allows the lungs to deflate. Although the involuntary respiratory control is most important during sleep and drug induced sedation or unconsciousness, it is also important in our minute-to-minute functioning while awake. It should be remembered that this system can be overridden by voluntary control. This is important as it allows us to talk.

CNS depressants can depress ventilation by a number of methods. The opioid drugs -- those which stimulate the mu receptors - depress the sensitivity this system has for pH changes. This leads to a situation where the volume of air moved is less for any given concentration of CO2, but as the level of CO2 rises the increase in respiration to this increase is much less than normal (the response curve is "shifted to the right" but the slope of the curve is also depressed). This can lead to high CO2 levels. If the CO2 exceeds concentrations of 10%, it too is a respiratory depressant. The mu antagonists have also been found to depress peripheral hypoxic drive.

Benzodiazepines, in contrast to the opioids, tend to depress the slope of the CO2 response curve but do not appear to shift it to the right. It is fairly difficult to cause serious problems to respiration with benzodiazepines, with the possible exception of midazolam.

One further drug deserves mention. Subanesthetic doses of nitrous oxide (30% to 60%), such as used for sedation in dental practice, have little if any influence on the CO2 response but have produced a 65% reduction in the hypoxic drive. This could present serious problems if a deeply sedated patient has had CO2 mechanism depressed by opioid drugs or is a COPD patient.

Adverse effects

Adverse effects have been reported in less than 4 percent of patients. Most adverse effects have been reported with greater doses, or when combined with other CNS depressants.

Our office offers an effective, efficient emergency protocol. This includes a person to be continuously in the room with the patient from the time of administration of the drug until they are judged able to leave the office. The patient should not be allowed to sleep at any time while in the office. Vital signs are usually taken at regular intervals, every 15 minutes or more often if there is any indication of over-sedation, i.e. tendency to sleep, etc.

Management of adverse reactions are planned before the drug is used and reviewed on a periodic basis. It should be noted that most adverse effects can usually be prevented by complete history-taking, physical examination and appropriate adjustment of drug dosage. Recognition of an emergency situation must be followed by initiation of a stabilization routine. This essentially entails the A-airway, B-breathing, and C-circulation of basic cardiac life support. Opening and maintaining a patient's airway is of paramount importance as is monitoring vital signs. Calling Emergency Medical Service by dialing 911 should follow if any doubt exists as to how to proceed.