chapter 34 Management of Emergencies
Despite efforts at prevention, complications and adverse drug reactions (ADRs) will arise during and after the administration of drugs for the management of pain or anxiety. In the office that has prepared for these situations, there is a greater likelihood of a successful outcome than in the unprepared or ill-prepared office. Many states, provinces, and specialty groups require that the dental office team be capable of correctly identifying and managing specific ADRs associated with parenteral sedation and general anesthesia.1,2 These emergencies are reviewed in this chapter.
Most ADRs are not life threatening. There are, however, potential responses that are life threatening, requiring immediate and effective management if the patient is to fully recover. These include the overdose reaction and the allergic response. A third, the idiosyncratic reaction, is also reviewed.
Overdose reaction (also known as “toxic reaction”) refers to those signs and symptoms manifested as a result of an absolute or relative overadministration of a drug producing elevated blood or plasma levels of that drug in specific organs (termed target organs) of the body. For central nervous system (CNS)–depressant drugs, an overdose occurs when the blood level of the drug becomes overly high in the cerebral circulation.4 Clinical manifestations of an overdose are related directly to the normal pharmacologic actions of the agent. For example, in therapeutic doses, barbiturates produce a mild depression of the CNS, which results in sedation or hypnosis (desirable effects). Barbiturate overdosage produces a more profound depression of the CNS, with respiratory or cardiovascular depression and a possible loss of consciousness.
Allergy is a hypersensitive state acquired through exposure to a particular allergen, reexposure to which brings about a heightened capacity to react.5 Clinically, there are a variety of manifestations through which allergy expresses itself. These include drug fever, angioedema, urticaria, dermatitis, depression of blood-forming organs, photosensitivity, and anaphylaxis. Certain drugs are more likely than others to elicit allergic reactions, and allergic reaction is theoretically possible with any substance.
In contrast to overdose, in which clinical manifestations are related directly to the pharmacology of the causative agent, the clinical response observed in an allergic reaction is mediated by an exaggerated response of the immune system. The degree of this response determines the severity of the allergic reaction. Allergic responses to a barbiturate, a local anesthetic, an antibiotic, a bee sting, peanuts, and shellfish are produced by the same mechanism and may appear clinically similar. Management of all allergic reactions is basically the same, whereas overdose reactions to the first three agents listed are quite dissimilar clinically and require different management.
Idiosyncrasy or idiosyncratic reactions are those ADRs that cannot be explained by any known pharmacologic or biochemical mechanism. Another definition is that an idiosyncratic reaction is any ADR that is neither an overdose nor an allergic reaction. An example of an idiosyncratic reaction is CNS stimulation (excitation or agitation) produced after the administration of a known CNS depressant such as a barbiturate.
Idiosyncratic reactions span an extremely wide range of clinical expression. For example, depression after administration of a stimulant, stimulation after administration of a depressant, and hyperpyrexia after administration of a muscle relaxant are all idiosyncratic reactions. It is usually impossible to predict in whom such reactions will develop or, indeed, the nature of the resulting idiosyncratic reaction.
Because of the unpredictability of the nature and occurrence of idiosyncratic reactions, their management is of necessity symptomatic. Of primary importance in the management of idiosyncrasy is basic life support (P → A → B → C): maintaining the airway and ensuring adequate ventilation and circulation, followed by “D” (definitive care). If seizures develop, management is based on airway maintenance and prevention of injury during the seizure.
It is thought today that virtually all instances of idiosyncrasy have an underlying genetic mechanism.6 These genetic aberrations remain undetected until the individual receives a specific drug, such as succinylcholine, which then produces its bizarre (nonpharmacologic) clinical expression.
Two major forms of ADR, overdose and allergy, are reviewed in this chapter; in addition, other emergency situations are discussed. Successful demonstration of the ability to manage these situations is frequently a requirement of the permitting process for parenteral sedation and general anesthesia. These complications are listed in Box 34-1.
Data from California State Board of Dental Examiners: Conscious sedation evaluation protocol, Sacramento, 2005; and American Association of Oral & Maxillofacial Surgeons: Office anesthesia evaluation manual, ed 6, Rosemont, Ill, 2006, The Association.
Emergency Situations Identified for Parenteral Sedation and General Anesthesia
Whenever CNS-depressant drugs are administered, the possibility may exist that an exaggerated level of CNS depression might develop. This might be noted clinically as a slightly oversedated patient, or it might result in an unconscious, apneic patient.
The group of drugs most likely to produce an overdose is the barbiturates. Barbiturates represented the first major breakthrough in the pharmacologic management of anxiety, and because of this, adverse reactions, such as allergy, addiction, and overdose, were tolerated. In the 1960s, with the introduction of the benzodiazepines (drugs that do not possess the same potential for abuse and overdose), barbiturate use declined. Description of their use in dentistry has been dropped from this edition. Previous editions of SEDATION, a Guide to Patient Management contain complete description of their use.7
Although the barbiturates present the greatest potential for adverse reaction, the opioid analgesics are involved with the greatest number of clinically significant episodes of overdose and respiratory depression. This is simply because opioids are more widely used than the barbiturates. As discussed elsewhere (see Chapters 7, 10, and 35), the use of opioids is popular in pediatric sedation. Opioids are often administered intravenously in conjunction with antianxiety drugs to aid in sedation and pain control in the adult patient. Goodson and Moore reported on 14 pediatric dentistry cases in which the administration of opioids (and other drugs) led to seven deaths and three instances of brain damage.8 Several opioids were implicated in these reactions: alphaprodine (7), meperidine (6), and pentazocine (1).
The clinical efficacy of a drug depends, in large part, on its absorption into the cardiovascular system and on subsequent blood levels of the drug in various organs of the body. Only the inhalation and intravenous (IV) routes of drug administration permit titration. With oral, intranasal (IN), and intramuscular (IM) administration, absorption is more erratic, as demonstrated by the wide range of variability in clinical effectiveness. The normal distribution curve becomes important when drugs are administered via those nontitratable routes. “Average” drug doses are based on this curve; therefore diazepam 5 mg orally, provides a desired effect (anxiolysis [minimal sedation]) in the majority of patients receiving it. For some patients (about 15% of the population), however, the 5-mg dose is ineffective; these patients require a larger dose to attain the same clinical effect. These patients, termed hyporesponders, are not at risk for potential overdose when given an average dose because a lack of adequate sedation is the clinical result.
The potential danger in the use of drugs lies with patients for whom an average 5-mg dose of diazepam is too great. These are persons who are quite sensitive (not allergic) to this drug and require smaller than usual doses to obtain clinically effective sedation, the so-called hyperresponders. It is normally not possible to predict the 15% of the population that will react in this manner. A history of a prior ADR may provide a clue to this occurrence. The medical history questionnaire should be examined carefully in relation to all prior drug reactions. When a history of drug sensitivity is obtained, great care should be exercised if barbiturates and opioid analgesics are to be used. Lower-than-average doses should be administered or different drug categories substituted. Nonbarbiturate sedative-hypnotic drugs, such as the benzodiazepines and the opioid agonist/antagonists, may be used in place of these drugs.
Although the clinical nature of the overdose cannot always be predicted, there is another way in which these drugs can produce this reaction—a way that is preventable. It relates entirely to the goal being sought by the dentist when these drugs are administered. Some clinicians administer CNS-depressants, such as barbiturates and opioids, seeking to achieve deep levels of sedation in more fearful patients. When these drugs are used in this manner via the oral, IN, or IM routes of drug administration, potential for overdose increases. Most dentists who administer barbiturates in their practices encounter patients who become uncooperative (less inhibited) after receiving these drugs. The planned procedure cannot be completed because of the difficulty in managing a patient who is slightly overdosed on barbiturates. Larger doses of the barbiturate given to a fearful patient in an attempt to produce deeper levels of sedation may produce greater degrees of CNS depression, with possible loss of consciousness and significant respiratory depression.
Administering any CNS depressant seeking to obtain deeper levels of sedation via routes of administration in which titration is not possible is foolhardy and an invitation to overdose. It can be neither recommended nor condoned. Only those techniques permitting titration should be used when deeper levels of sedation are sought, and then only when the dentist and entire sedation team are thoroughly familiar with both the technique and the drugs to be administered and are able to manage all possible complications associated with the procedure.
The inhalation and IV routes are the only routes that permit titration. A factor to be remembered regarding inhalation and IV sedation is that absorption of the drugs into the systemic circulation occurs rapidly, so drug responses (both therapeutic as well as adverse) develop suddenly. Titration remains the greatest safety feature these techniques possess and should always be used when possible. Table 34-1 summarizes the recommendations made throughout this book for the various routes of drug administration.
Barbiturates produce depression of a number of physiologic properties, including nerve tissue; respiration; and skeletal, smooth, and cardiac muscle. The mechanism of action (sedation and hypnosis) is depression at the level of the hypothalamus and the ascending reticular activating system (RAS), which produces a decrease in the transmission of impulses to the cerebral cortex. Further increases in barbiturate blood level produce depression at other levels of the CNS, such as profound cortical depression, depression of motor function, and finally depression of the medulla. This is represented diagrammatically as follows:
Minimal-to-moderate sedation (calming) → Moderate-to-deep sedation (hypnosis, sleep) → General anesthesia (unconsciousness with progressive respiratory and cardiovascular depression) → Respiratory arrest
At low (therapeutic) blood levels the patient appears calm and cooperative (minimal-to-moderate sedation). As the CNS-depressant drug level in the cerebral circulation increases, the patient falls into a rousable sleep (moderate-to-deep sedation). The dentist will notice the patient’s inability to keep his or her mouth open despite reminders to do so.
In addition, when barbiturates are administered, patients at this level of barbiturate-induced CNS depression tend to overreact to stimulation, especially noxious stimulation. An unsedated adult patient may grimace in response to a painful stimulus; an adult moderately to deeply sedated with barbiturates commonly demonstrates an exaggerated response, perhaps yelling or jumping. This reflects a loss of self-control over emotion that is associated with the CNS-depressant action of the barbiturate. This reaction to noxious stimuli is extremely uncommon when benzodiazepines are administered for sedation.
With continued elevation of the barbiturate blood level, hypnosis (sleep) ensues, with a minor degree of respiratory depression (decreased depth and increased rate of ventilation). At this level of CNS depression, there is usually no adverse action on the cardiovascular system, only a slight decrease in blood pressure and heart rate, similar to that occurring in normal sleep. Dental treatment cannot be continued at this level of CNS depression because the patient is unable to cooperate with the dentist by keeping his or her mouth open and may require assistance in maintaining airway patency (head-tilt). The patient still responds to noxious stimulation but in a sluggish manner. This patient requires rescue from deep sedation until such times as they return to moderate sedation levels.
With further elevation of the barbiturate blood level, the degree of CNS depression broadens so that the patient is now unconscious (incapable of response to sensory stimulation, loss of protective reflexes with attendant inability to maintain an airway). Spontaneous respiratory efforts may still be present; however, with even further increase in barbiturate blood levels, medullary depression occurs, which is clinically evident as respiratory and cardiovascular depression. Respiratory depression is noted as shallow breathing movements at a slow or rapid rate. Ventilatory excursions of the chest are not an indication that air is entering or leaving the lungs but only that the patient is trying to bring air into the lungs. Cardiovascular depression is evident as a continued decrease in blood pressure (caused by medullary depression and direct depression of the myocardium and vascular smooth muscle) and an increased heart rate. The patient develops a shocklike appearance and has a weak and rapid pulse and cold, moist skin.
As the barbiturate blood level continues to increase, or if the patient is not managed adequately in the previous stage, respiratory arrest will occur. Respiratory arrest is readily managed with controlled ventilation. If ventilation is not adequately provided, cardiac arrest will ensue.
Other nonbarbiturate sedative-hypnotic drugs (i.e., benzodiazepines) also possess a potential to produce overdose, although this is quite a bit less likely to occur as with the barbiturates. The potential for overdose varies greatly from drug to drug, and to varying degrees all sedative-hypnotic drugs have this potential.
Meperidine, like most opioid agonists, exerts its chief pharmacologic actions on the CNS. Therapeutic doses of meperidine produce analgesia, sedation, euphoria, and a degree of respiratory depression. Of principal concern, of course, is the respiratory depressant action of the opioid agonists. They are direct depressants of the medullary respiratory center. In humans respiratory depression from opioid agonists is evident even at doses that do not disturb the level of consciousness. Respiratory depression produced by opioids is dose dependent: The larger the dose, the greater the level of respiratory depression. The opioid agonist/antagonists nalbuphine and butorphanol offer the combination of analgesia and sedation with minimal respiratory depression.
Death from opioid overdose almost always results from respiratory arrest. All phases of respiration are depressed: rate, minute volume, and tidal volume. The respiratory rate may fall below 10 breaths per minute. Rates of 5 to 6 breaths per minute are not uncommon. The cause of this decreased respiratory rate is a reduction in responsiveness of the medullary respiratory centers to increases in carbon dioxide tension (Pco2) and also a depression of the pontine and medullary centers that are responsible for respiratory rhythm.
The cardiovascular effects of meperidine are not clinically significant when the drug is administered within its usual therapeutic dose range. Following IV administration of meperidine, however, there is normally an increase in the heart rate produced by the atropine-like vagolytic properties of meperidine. Even at overdose levels the blood pressure remains quite stable until late in the course of the reaction, when it falls, primarily as a result of hypoxia. The administration of O2 at this time will produce an increase in blood pressure despite continued medullary depression. Overly high blood levels of opioid agonists can lead to loss of consciousness.
Overdose reactions to both the sedative-hypnotics and opioid agonists are produced by a progressive depression of the CNS that is manifested by alterations in the level of consciousness and as respiratory depression that ultimately results in respiratory arrest. The loss of consciousness produced by barbiturates or opioid agonists is not always the result of unintentional overdose—these drugs are commonly administered as the primary agents in general anesthesia (see Chapter 31). However, when moderate sedation is the goal, unintended loss of consciousness and respiratory depression/arrest must be considered as complications of drug administration.
The duration and the degree of this clinical reaction vary according to the route of administration, the dose administered, and the patient’s individual sensitivity to the drug. In most situations oral and rectal administration result in reduced CNS depression but with a longer duration; IM, IN, and submucosal administration result in a more profound level of depression of relatively long duration, whereas IV administration produces the most profound level of depression, but of shorter duration than that seen with the other techniques. The onset of respiratory depression after IV administration may be quite rapid, whereas that following oral or rectal administration is considerably slower. Onset is intermediate in IM, IN, and subcutaneous administration.
Management of sedative-hypnotic drug overdose is predicated on correcting the clinical manifestations of CNS depression. Stated another way, according to the “new” definitions of sedation from the American Society of Anesthesiologists9 and the American Dental Association,10 the dentist administering sedation must be capable of “rescuing” the patient who inadvertently descends into a level of CNS-depression beyond that which is intended.
Of primary importance is recognition and management of respiratory depression through the administration of basic life support (BLS). Benzodiazepines can be reversed through administration of the specific reversal agent, flumazenil. Unfortunately, there is no effective antagonist that reverses the CNS-depressant properties of the barbiturates.
(From Malamed SF: Medical emergencies in the dental office, ed 6, St Louis, 2007, Mosby.)
The patient might be more deeply sedated and barely responsive to stimulation, with a partially or totally obstructed airway. In this situation assisted ventilation is essential in addition to airway maintenance. With patency of the airway ensured, the patient should receive oxygen via full-face mask or nasal hood. If spontaneous breathing is present but shallow, assisted positive-pressure ventilation is indicated. This is accomplished by activating the positive-pressure mask just as the patient begins each respiratory movement (just as the chest begins to expand). The positive-pressure mask is activated by depressing the button on top of the mask until the patient’s chest rises and then releasing the button. With the self-inflating bag-valve-mask device, the bellows bag is squeezed at the start of each inhalation. With both devices, an airtight seal of the mask and head-tilt must be maintained at all times. If respiratory arrest occurs (no visible respiratory efforts), controlled artificial ventilation (rescue breathing) must be initiated. The recommended rate for the adult is one breath every 5 seconds (12 per minute) and one breath every 3 seconds for the child aged 1 to 8 years (20 per minute) and the same rate for the infant younger than 1 year old (20 per minute).11 Expansion of the patient’s chest is the only sure sign of successful ventilation. Overinflation should be avoided as this leads to abdominal distention, resulting in inadequate ventilation and an increased risk of regurgitation.
In most cases of barbiturate or nonbarbiturate sedative-hypnotic (e.g., benzodiazepine) drug overdose, the patient can be managed in this manner until the cerebral blood level of the drug decreases and the patient returns to the desired level of CNS-depression (consciousness returns) or until emergency assistance arrives. Recovery occurs as a result of redistribution of the drug within compartments in the body, not biotransformation. The patient becomes more alert and responsive, breathing improves (becomes deeper), and if the blood pressure had been depressed, it returns to near baseline levels. The length of time for this process to occur depends on the drug administered (short-acting versus long-acting drug) and its route of administration.
Benzodiazepine overdosage may be reversed by IV or IM administration of flumazenil, a specific benzodiazepine antagonist. Flumazenil is administered intravenously at a dosage of 0.2 mg in 15 seconds, waiting 45 seconds to evaluate recovery. If recovery is not adequate at 1 minute, an additional dose of 0.2 mg may be administered. This is repeated every 5 minutes until recovery occurs or a dose of 1.0 mg has been delivered.12
Management of Sedative-Hypnotic Overdose
Most cases of sedative-hypnotic overdose involving benzodiazepines are considerably less severe, with diminished responsiveness and slight respiratory depression noted. Management consists of positioning, airway maintenance, and assisted ventilation until recovery. Emergency medical assistance is not usually required. Before discharge in the custody of a responsible adult, the patient must be capable of standing and walking without assistance. In no circumstance should the patient be discharged alone or if not adequately recovered.
Drugs used in management include oxygen and, if benzodiazepines are involved in the overdose, flumazenil. The need for medical assistance with altered consciousness varies with the training and experience of the dentist.
Oversedation and respiratory depression are the primary clinical manifestations of opioid overdose. Cardiovascular depression typically does not develop until late in the opioid overdose reaction, especially if the patient is placed in a supine position. Management of the patient who has received an absolute or relative overdose of an opioid is similar to that described for the sedative-hypnotic drugs with one major addition: A specific antagonist is available to reverse the clinical actions of opioid agonists.
In most cases of opioid overdose the patient remains conscious, although not fully alert or as responsive. Assistance in airway maintenance may be desirable (e.g., head tilt–chin lift). With more profound depression, unconsciousness and respiratory arrest may occur, necessitating reassessment of airway and breathing. Because the cardiovascular system is relatively unaffected by opioid overdose if oxygenation is maintained (airway patency and adequate ventilations are maintained), especially in the supine patient, the blood pressure and heart rate should remain close to baseline values.
Following IV administration, naloxone’s actions are noted within 1 to 2 minutes (if not faster) and within 10 minutes following IM administration (in the presence of a near-baseline blood pressure). Naloxone is available in a 1-ml ampule containing 0.4 mg (adult dosage form) or 0.02 mg (pediatric dosage form). The drug is loaded into a plastic disposable syringe, and when the IV route is available, 3 ml of diluent (any IV fluid) is added to the syringe, producing a final concentration of 0.1 mg/ml of naloxone (adult) or 0.005 mg/ml (pediatric). The drug is then administered intravenously to the adult at a rate of 1 ml/min until the ventilatory rate and alertness increase. In children the IV dose is 0.01 mg/kg.13 If naloxone is administered intramuscularly, a dose of 0.4 mg (adult) or 0.01 mg/kg (pediatric) is administered into a suitable muscle mass, such as the middeltoid (adult) or vastus lateralis (child or adult), or sublingually (if the patient is unconscious).
A potential problem when reversing opioid overdose with naloxone is the fact that its duration of clinical activity may be shorter than that of the opioid it is being used to reverse. This is especially true in cases in which a longer-acting opioid agonist such as morphine is administered; it is less likely to occur with meperidine and even more unlikely with fentanyl and its analogs alfentanil, sufentanil, and remifentanil. When the opioid action is of greater duration than the intravenously administered naloxone, the dentist and staff will notice an initial improvement in the patient’s clinical picture as the naloxone begins to act and then see a recurrence of CNS depression approximately 10 minutes or more later (following IV administration of naloxone). Because the opioid producing the overdose continues to undergo redistribution and biotransformation during this time, in the event that such a rebound effect does occur, it would quite likely be much less intense than the initial response. In cases in which longer-acting opioids (e.g., morphine) have been administered intramuscularly or submucosally, it is recommended that the initial IV dose of naloxone be followed with an IM dose (0.4 mg [adult] or 0.01 mg/kg [pediatric]). In this way, as the clinical action of the IV naloxone dose is waning, the level of naloxone from the IM dose will be reaching a peak, minimizing the likelihood of a relapse of significant respiratory or CNS depression. The administration of naloxone in opioid overdose is important but not the most critical step in overall patient management (see later discussion).
Box 34-3 outlines the steps to follow in management of opioid overdose.
Management of Opioid Overdose
The previous discussions dealt with overdose reactions of varying levels of severity that occur after the administration of a single drug. Although single-drug overdose can and does occur, especially after IM, IN, or submucosal administration (because of the inability to titrate to effect), many overdose reactions reported involve the administration of multiple drugs. In many of these cases, drugs such as an antianxiety drug are combined with an opioid to provide a level of sedation and some analgesia. A local anesthetic is then added to manage operative pain. Drugs in all three of these categories are CNS depressants. Added to this, in many cases, will be nitrous oxide (N2O) and oxygen (O2), adding yet another degree of CNS depression.
Whenever more than one CNS-depressant drug is administered to a patient, the dosages of all drugs must be reduced from their usual dosage to prevent exaggerated, undesirable clinical responses. As demonstrated in Table 34-2, in most of the cases reported by Goodson and Moore, this step was not taken, with disastrous results often occurring.8
Another factor must be considered, one that most health professionals do not, as a rule, give much thought when using sedative techniques: Local anesthetics themselves are CNS depressants and can produce additive actions when administered in conjunction with drugs commonly used for sedation. The maximal dosage of local anesthetic to be administered to any patient, but especially to a child or lighter-weight adult, should be based on the patient’s body weight in kilograms (or pounds). When no other CNS depressants are being administered, this maximal dose could be reached without adverse effects if the patient is an American Society of Anesthesiologists (ASA) 1 and falls within the normal responding range on the bell-shaped curve. Table 34-3 presents the maximal recommended doses of the most commonly used local anesthetics. When a local anesthetic is administered with other CNS depressants, the local anesthetic dosage should be minimized.
A primary goal of moderate sedation is to produce a cooperative patient who still possesses their protective reflexes (e.g., swallowing, coughing, maintenance of the airway). If possible, this goal should be achieved using the simplest technique available, as well as the fewest drugs possible. Polypharmacy, the combination of several drugs, is necessary in many patients to achieve the desired level of sedation and/or analgesia. The use of drug combinations, however, increases the opportunity for ADRs while making it less obvious which drug might be responsible for any problems that arise, thereby making management of the situation more complicated.
Within the individual techniques of sedation, it is suggested that single-drug regimens are preferable to combinations of drugs. Rational drug combinations are available for use in certain situations in which they are specifically indicated. With IV drug administration, the problem of severe ADRs should not occur if the technique of titration is strictly adhered to at all times. Titration is not possible with the IM, IN, and oral routes of administration. The dentist must modify individual drug dosages before their administration. Serious ADRs are more likely to occur when the technique used was one in which titration was not possible.
Consideration must also be given to the use of multiple techniques of sedation, as opposed to multiple drugs by one technique of administration. It is not uncommon for patient who is a significant management problem to receive an oral antianxiety drug before arrival at the office. This is followed by either IM, IN, or IV sedation, and inhalation sedation and local anesthesia during the course of treatment. Whenever oral sedation with CNS depressants is used, the dosages of all subsequent CNS depressants should be evaluated carefully before their administration. This is critical when nontitratable routes of drug administration are used. With inhalation and IV sedation, careful titration of CNS-depressant drugs to the patient who has previously received oral premedication will usually produce the desired level of clinical sedation with minimal risk of adverse response by the patient.
When possible, fixed-dose administration of drugs based on a range of ages (e.g., 4 to 6 years: 50 mg) should not be used. Dosages based on body weight or surface area of the patient, or titration, are preferred when possible.
Should the selected drug dosage administered in a non-titratable technique prove to be inadequate to produce the desired effect in the patient, it is prudent to consider a change in the sedation technique or in the drugs being used (at a subsequent appointment) rather than increasing the drug dosage to a higher and potentially more dangerous level at the same visit.
The Dentists Insurance Company (TDIC), in a retrospective study of deaths and morbidity in dental practices over a 3-year period, concluded that in most of those incidents related to administration of drugs, there were three common factors.14
An overdose reaction to the administration of CNS-depressant drugs may not always be a preventable complication; however, with care taken on the part of the dentist, the incidence of these events should be extremely low, with a successful outcome the result virtually every time. With techniques such as IV and inhalation sedation, in which titration is possible, overdosage should be rare. With oral, IM, and IN drug administration, in which little control is maintained over the drug’s ultimate effect because of the inability to titrate, the dentist must expend greater care in the preoperative evaluation of the patient, in the determination of the appropriate drug dosage, and in monitoring during the procedure so that excessive CNS or respiratory depression may be identified and treated immediately. When the oral, IN, or IM routes are used, the onset of adverse reactions may be delayed. An adverse reaction may not develop until after the rubber dam is in place and the dental procedure has been started. Therefore monitoring of the patient throughout the procedure becomes extremely important to the patient’s safety. My preferences, as of April 2009, in monitoring during parenteral minimal or moderate sedation are as follows:
Allergy is a hypersensitive state acquired through exposure to a particular allergen, reexposure to which produces a heightened capacity to react. Allergic reactions cover a broad range of clinical manifestations, from mild, delayed-onset reactions occurring as long as 48 hours after exposure to immediate and life-threatening reactions developing within seconds of exposure. Although all allergic phenomena are important and require thorough evaluation by the dentist, only one form, the type I, or immediate, reaction is discussed here, for it may present the dentist with a life-threatening emergency situation. A classification of allergy types is presented in Table 34-4.
Allergic reactions are mediated through immunologic mechanisms that are similar regardless of the specific antigen responsible for precipitating the response. Therefore an allergic reaction to the venom of a stinging insect may be identical to that seen after aspirin or penicillin administration in a previously sensitized individual. Allergic reactions must be differentiated from the overdose, or toxic, reaction previously discussed, in which the observed signs and symptoms are a direct extension of the normal pharmacologic properties of the drug administered. Overdose reactions are much more commonly encountered than are allergic drug reactions. Of all ADRs, 85% result from the pharmacologic actions of drugs; 15% are immunologic reactions.15 To the layperson, however, any adverse drug response is frequently labeled “allergic.”
Allergy is a frightening word to those health professionals responsible for primary care of patients. Although none of the drugs commonly used for the management of pain and anxiety has a significantly high rate of allergenicity, allergic phenomena may still arise. The only drugs mentioned in this book that, to my knowledge, have never been shown to have produced allergy are N2O and O2. Although the concept of prevention has been stressed repeatedly throughout this text, in no other situation is this concept of greater importance than with allergy. Although allergy is not the most common ADR, it is frequently involved with the most serious of these reactions.
Of the many antianxiety drugs used, the barbiturates probably possessed the greatest potential for sensitization of patients. Although not nearly as common as allergy to penicillin or aspirin, barbiturate allergy usually manifests itself in the form of skin lesions, such as hives and urticaria, or less frequently in the form of blood dyscrasias, such as agranulocytosis or thrombocytopenia. Allergy to barbiturates occurs much more frequently in persons with a history of asthma, urticaria, and angioedema.16 A documented history of allergy to any barbiturate represents an absolute contraindication to their administration.
Amongst the opioids, meperidine can release histamine locally. When meperidine is administered intravenously, this localized histamine release develops along the path of the vein through which the drug travels. This reaction is not an allergy and requires no therapeutic management. The reaction resolves after the drug leaves the area of its administration. Use of meperidine is relatively contraindicated in asthmatic patients because of potential bronchospasm induced by histamine release when the drug enters the pulmonary circulation.
Following IV administration, atropine—an anticholinergic—may produce flushing of a patient’s face, neck, and upper chest. Known as atropine flush, this is not an allergic reaction and requires no therapeutic intervention because spontaneous resolution occurs within a brief time. Atropine flush is most often seen with overdose of atropine. However, in certain sensitive individuals (those who are hyperresponders on the bell-shaped curve), the usual therapeutic dose may provoke this response.
Whenever any drug or combination of drugs is being considered for administration, the dentist must question the patient about any prior exposure to that drug or members of the same drug family. In addition, the patient’s medical history questionnaire must be evaluated. All questionnaires include questions concerning current drug use and prior ADRs. These two steps will, in most cases, enable the dentist to assess the possibility of an adverse drug response. Should a positive history be elicited, questioning is undertaken to determine the nature of the previous reactions. Although the questioning may vary, basic questions asked include the following:
The need for hospitalization or assistance from a second health professional usually indicates that a more serious ADR occurred. If possible, it would be prudent to speak directly to the doctor involved with the patient at that time.
Following a thorough dialogue history and review of the medical history questionnaire, it is usually possible to form a general opinion about the true nature of the reaction. If the dentist is convinced that an allergy did occur, other drugs that are structurally dissimilar to the offending drug should be selected for administration. In most cases, however, it will become obvious that the “allergy” was in fact a side effect of the drug (e.g., nausea from codeine) or that the response was psychogenic (i.e., induced by anxiety). If doubt remains as to the precise nature of the reaction, the patient should be managed, at that time, with drugs unrelated to the one(s) in question, followed by consultation with an allergist (or other appropriate individual) so that more definitive testing might be undertaken.
Most serious (i.e., life-threatening) allergic drug reactions are immediate, in particular the type I, or anaphylactic, reaction. The term immediate, relating to allergic phenomena, indicates the development of clinical signs and symptoms within 60 minutes of exposure to the allergen.
A number of organs and tissues are affected during immediate allergic reactions, particularly the skin, respiratory system, cardiovascular system, and gastrointestinal tract. Generalized, or systemic, anaphylaxis, by definition, affects all the systems mentioned. If hypotension is also a clinical component of the response, the term anaphylactic shock is correctly applied.
Immediate allergic reactions also manifest through any number of combinations involving these organs. Reactions involving one system are referred to as localized anaphylaxis, for example, asthmatic attack, in which the respiratory system is the sole target, or urticaria, in which the skin is the target organ.
The time elapsing between exposure of the patient to the antigen and the development of clinical signs and symptoms is of great importance. As a rule, the more rapidly signs and symptoms evolve after exposure to an allergen, the more intense the ultimate response will be. Conversely, the greater the length of time is between exposure and onset, the less intense the reaction usually is. However, cases of anaphylaxis have been reported to arise many hours after exposure. Of importance, too, is the rate at which signs and symptoms progress once they appear. If they appear and increase in severity rapidly, the reaction is more likely to become life threatening than one that progresses slowly or not at all.
Allergic skin reactions are the most common sensitization reaction to drug administration. Many types of allergic skin reaction may occur, the two most important types being localized anaphylaxis and drug eruption. Drug eruption constitutes the most common group of skin manifestations of drug allergy. Included in this category are urticaria, erythema (reddening), and angioedema (localized swelling).
Urticaria is associated with wheals (smooth, slightly elevated patches of skin) and often with intense itching (pruritus). Angioedema is a process in which localized swelling occurs in response to an allergen. Several forms of angioedema exist, but clinically they appear to be similar. The skin is usually of normal color (unless accompanied by urticaria or erythema) and temperature, and pain and itching are uncommon. The areas most commonly involved are the hands, face, feet, and genitalia. Of special concern is the potential involvement of the lips, tongue, pharynx, and larynx, leading to obstruction of the airway (laryngeal edema).
Allergic skin reactions, if the sole manifestation of allergy, are usually not considered life threatening. However, a skin reaction that develops rapidly after drug administration may be the first indication of the generalized reaction to follow.
Adhesive tape used during IV sedation is a fairly common cause of dermatologic reactions, the adhesive being the allergen. The usual response to this tape is erythema and urticaria developing around the site where the tape has been placed. In adhesive-allergic individuals, hypoallergenic tapes are recommended for use.
Clinical signs and symptoms of allergy may be related entirely to the respiratory tract, or signs and symptoms of respiratory tract involvement may develop along with other systemic responses. In a slowly developing generalized allergic reaction, respiratory tract involvement usually follows the skin response but precedes cardiovascular signs and symptoms. Bronchospasm is the classic respiratory manifestation of allergy. It represents the clinical result of constriction of bronchial smooth muscle. Signs and symptoms include respiratory distress, dyspnea, wheezing, flushing, possible cyanosis, perspiration, tachycardia, greatly increased anxiety, and the use of accessory muscles of respiration.
A second respiratory manifestation of acute allergy may be the extension of angioedema to the larynx, producing a swelling of the vocal apparatus with subsequent obstruction of the airway (laryngeal edema). Clinical manifestations include little or no air exchange from the lungs (chest is not moving, little or no air is felt); wheezing, indicative of partial airway obstruction; or no sound, indicating total obstruction. The occurrence of significant angioedema represents one of the most ominous of clinical signs. Acute airway obstruction leads rapidly to the death of the patient unless immediately corrected.
Generalized anaphylaxis is the most dramatic and acutely life-threatening form of allergy and may lead to clinical death within a few minutes. It may develop after the administration of an antigen via any route but is most likely to occur after parenteral administration. The time from antigenic challenge to the onset of reaction varies greatly, but typically the reaction develops rapidly, reaching a maximum within 5 to 30 minutes. Delayed responses of 1 hour or more have been reported. It is believed that this is the result of the rate at which the antigen enters into the circulatory system.
Signs and symptoms of generalized anaphylaxis are highly variable. Four major clinical syndromes are recognized: skin reactions, smooth muscle spasm (gastrointestinal and genitourinary tracts and respiratory smooth muscle), respiratory distress, and cardiovascular collapse. In typical generalized anaphylaxis, the symptoms progressively move through these four areas; however, in cases of fatal anaphylaxis, respiratory and cardiovascular disturbances predominate and are evident early in the reaction.
In the typical generalized anaphylactic reaction, the patient may begin to complain of feeling sick with intense itching, flushing, and giant hives developing over their face and upper chest. Nausea, possibly followed by vomiting, may also occur. These early symptoms are primarily related to the skin. Other responses noted early in the reaction include conjunctivitis, vasomotor rhinitis (increased mucus secretion in the nose), and pilomotor erection (the feeling of hair standing on end).
Associated with the development of skin symptoms are various gastrointestinal and genitourinary disturbances related to spasm of smooth muscle. Severe abdominal cramps, nausea and vomiting, diarrhea, and fecal and urinary incontinence may occur.
Respiratory symptoms normally follow. However, in rapidly developing reactions, all symptoms may occur within a short time with considerable overlap. In particularly severe reactions, respiratory and cardiovascular symptoms may be the only signs present.
Respiratory symptoms begin with a feeling of substernal tightness or pain in the chest. A cough may develop in addition to wheezing and dyspnea. If the respiratory disturbances are severe, cyanosis may develop, noted initially in mucous membranes and nail beds. Laryngeal edema may also develop, producing acute airway obstruction.
Signs and symptoms of cardiovascular disturbance follow and include pallor, lightheadedness, palpitation, tachycardia, hypotension, and cardiac dysrhythmias, followed by loss of consciousness and cardiac arrest. With loss of consciousness, the anaphylactic reaction may more properly be called anaphylactic shock.