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W2325323170 abstract "“Was it a vision, or a waking dream? Fled is that music: — Do I wake or sleep?”The Eve of St. Agnes John Keats Since the advent of pediatric gastrointestinal endoscopy in the early 1970s, there has been a remarkable increase in the number of diagnostic and therapeutic procedures performed in infants and children (1). Commensurate with the increase in use has been the recognition that performance of endoscopy in children requires more patience, experience, and expertise than in adults (2). For example, there is a common wisdom that infants neither respond to nor remember painful experiences, but this is simply not true (3). Endoscopic procedures may be associated with discomfort and anxiety. Painful procedures have been shown to result in short-term physiologic changes (4) and possible long-term behavioral changes (5), and the response to painful stimuli may be greatly exaggerated in children (6). In recognition of these physiologic and psychological differences, the pediatric endoscopist must exercise appropriate clinical judgment in patient selection and must demonstrate adequate cognitive and technical competency for accomplishing a successful and safe procedure (7,8). Depending on the type of endoscopic procedure, children may require no sedation, conscious sedation, or general anesthesia (GA) (9–11). When appropriate analgesia and amnesia are ensured in children, anxiety is greatly diminished (12). This is a review of conscious sedation for endoscopy and a discussion of the rationale for sedation techniques in children. The terms “conscious sedation” and “deep sedation” are used to categorize the physiologic effects of sedatives. It must be emphasized that these states lie along a continuum of the degree of sedation, ranging from light, or conscious sedation to GA (13). After administration of any sedative, the level of consciousness is not predictable, and a sedated child may vacillate between different degrees of consciousness during the procedure. The American Academy of Pediatrics has defined conscious sedation as a minimally depressed level of consciousness that retains the patient's ability to maintain a patent airway independently and continuously and to respond to physical stimulation and/or verbal command. (13) Deep sedation is defined as a state of depressed consciousness or unconsciousness from which the patient is not easily aroused. It may be accompanied by partial or complete loss of protective reflexes, with inability to maintain a patent airway independently or respond purposefully to physical stimulation or verbal commands. (13) General anesthesia is defined as a controlled state of unconsciousness accompanied by a loss of protective reflexes including the ability to maintain an airway independently and to respond purposefully to physical stimulation or verbal command (14). The method of sedation for endoscopy, whether conscious sedation, deep sedation, or GA, is really a matter of choice (15–17). Many factors must be considered, including the patient's condition (American Society of Anesthesiology [ASA] classification), (18) the type of procedure (diagnostic vs. therapeutic), the anticipated level of cooperation from the patient, the parents' and patient's preference after they have been provided these choices and explanation of the risks, and the endoscopist's personal preference based on experience. There is a consensus that GA is necessary for complicated therapeutic procedures, for patients with neurologic problems, for patients at high risk for cardiopulmonary complications, and for uncooperative patients in whom intravenous (IV) sedation has failed (4,10,19). However, there are no rules regarding the choice between conscious sedation or GA (15–18). Chuang et al. (20) reported their experience in 614 children between 1 and 18 years of age with the use of meperidine, midazolam, or fentanyl in different combinations and suggested that IV sedation (IV-s) was safe, effective, and less costly than GA. In a large, retrospective study of 2711 upper and lower endoscopic examinations in patients more than 12 years of age, Balsells et al. (11) reached conclusions similar to those of Chuang et al. and used IV-s in 96.5% of patients and GA in 3.5% of patients. Squires et al. (21) performed a prospective study on 226 patients less than 18 years of age comparing efficacy, safety, and cost of performing endoscopic procedures in patients under IV-s versus those under GA. The costs of GA were predictably higher; however, the procedure room time for patients under IV-s sedation less than 2 years of age and between 6 and 9 years of age were significantly longer than for patients evaluated under GA (75 ± 10 vs. 44 ± 7 minutes, respectively [P < 0.007] for patients aged less than 2 years; and 84 ± 8 vs. 58 ± 7 minutes, respectively [P < 0.01] for patients aged between 6 and 9 years). Unfortunately, the issue of postprocedure amnesia was not investigated (11,21). The purpose of performing a procedure is not only to establish diagnosis and/or therapy in a timely manner but also to ensure the patient's comfort and anxiolysis. In approximately 18% of patients receiving IV-s in the series by Squires et al., (21) the procedure was completed with additional physical restraint while the patients continued in an agitated state, and in 5% of patients the procedure had to be aborted (21). It is obvious that for every patient, an individual decision must be made regarding use of IV-s versus GA. PREPARATION OF THE PATIENT AND PARENTS The physician must obtain a thorough history, perform a complete physical examination, and obtain appropriate laboratory tests before deciding about the procedure. Table 1 lists the potential risk factors for complications during endoscopic procedures. It is advisable to categorize the patient according to the guidelines of the ASA to determine whether to use IV-s or GA (18) (Table 2). It is usually safe to sedate the patients belonging to ASA classes 1 and 2. The indications, expected duration, potential risks and complications of the procedures and of sedation must be explained in detail to the patient and parents as appropriate and an informed consent obtained (22–24). A team approach involving the patient, nurse, and physician is essential to ensure the safety and efficacy of the procedure.TABLE 1: Potential risk factors for complications during endoscopyTABLE 2: American Society of Anesthesiologists (ASA) physical status classificationFASTING GUIDELINES Traditionally, fasting for solids for 6 hours and liquids for 2 to 4 hours is recommended (8,25,26). However, longer periods of fasting may be required for conditions such as achalasia and gastric outlet obstruction, because retained food in the esophagus or stomach may increase the risk of aspiration. PREPARATION FOR THE PROCEDURE Specific considerations regarding adequate facilities, backup emergency devices, equipment, and education and training have been reviewed elsewhere and are beyond the scope of this discussion (13,23,24). A minimum of three people should be available to perform the procedure safely and effectively: the endoscopist, the monitor or the endoscopy nurse to observe appropriate physiologic variables and to assist in any support or resuscitative measures required, and an assistant in performance of biopsies and specimen collection. The endoscopist and monitor must be present from the time of administration of the sedative medication until recovery is judged adequate (23,24). Premedications are not routinely used in pediatric endoscopic procedures. A study on the use of atropine as an adjunct to conscious sedation in children undergoing esophagogastoduodenoscopy (EGD) did not demonstrate benefit (27). However, a placebo-controlled trial of oral midazolam as a premedication in children undergoing EGD was effective in decreasing patient anxiety and facilitated preprocedural preparation (28). There is no consensus on the use of pharyngeal anesthesia. Some do not advocate pharyngeal anesthesia, because they believe that many children become more excited after losing the swallowing sensation (29) Others have noted greater agitation after pharyngeal stimulation from the endoscope, and therefore use topical pharyngeal anesthesia routinely (22,30). An adequate IV line with free-flowing blood return to minimize local phlebitis should be established and either kept running or “heplocked” for future access if needed. Continuous monitoring of pulse rate, respiration, blood pressure, and transcutaneous oxygen saturation should be started before injecting the sedatives. An experienced nurse should meticulously monitor the patient's color, respiratory effort, and peripheral perfusion (31). Most complications of pediatric endoscopy are secondary to sedation and are often related to hypoxemia, which may not be recognized by even experienced personnel in absence of pulse oximetry (32). Introduction of the endoscope orally causing tracheal compression, size and endoscope looping causing pain, anemia, obesity, and a history of smoking have all been reported as adverse events (33–36). Several pediatric studies have noted the frequency of oxygen desaturation during EGDs (31,37,38) and suggest oxygen desaturation may be more common with conscious sedation (39). Which patient will have such a problem can never be predicted with certainty, and universal monitoring of patients should therefore be the rule. The most common adverse effect of brief hypoxemia on cardiac rhythm is tachycardia (2,38). This may be prevented by using supplemental oxygen with a nasal cannula or blow-by technique. With intraprocedural desaturation to less than 90% for more than 30 to 45 seconds, oxygen should be administered and if Sao2 does not improve, the endoscope should be removed. Table 3 lists potential complications related to sedation. Ineffective sedation is a more common problem than oversedation and hypoxemia in children, because the metabolism of these medications is different than in adults. The effect of a drug at a particular milligram per kilogram dose is much less predictable when absorbed across a mucus membrane than when administered parenterally. Slow titration of a drug is only possible using the IV route. If there is reluctance to provide higher than expected doses based on adult guidelines, the pediatric gastroenterologist may have a combative patient. This stems directly from several age-dependent factors influencing the pharmacokinetics and pharmacodynamics of these drugs, including the greater relative permeability of the blood–brain barrier in neonates for narcotics and barbiturates and maturational changes in hepatic enzyme activities and renal function (8,22). Careful titration of medication dosages to achieve the desired pharmacologic effect in each child is therefore key in providing safe and successful conscious sedation.TABLE 3: Potential complications associated with sedationAGENTS FOR CONSCIOUS SEDATION The perfect conscious sedation regimen should confer a predictable level of sedation, have a broad therapeutic window, and possess a consistent dose–response relationship (40). Further, the drugs used should render the child devoid of anxiety, create anterograde amnesia for the duration of the procedure, avoid cardiovascular and respiratory depression, be nonirritating during injection, possess a rapid onset of action, and provide smooth postprocedural recovery without side effects (22,40). Unfortunately, such an ideal drug does not exist. However, a wide variety of agents are available for conscious sedation of children. Dosages of the more commonly used drugs, their side effects, and other precautions inherent in their use are listed in Table 4(22,41–45).TABLE 4: Common agents for conscious sedation in pediatric endoscopyIn general, the most common sedation cocktails used for pediatric endoscopy combine a narcotic analgesic (e.g., meperidine or fentanyl) with a benzodiazepine (diazepam or midazolam). These latter agents provide sedation and amnesia but no analgesia (8). Administration of the narcotic agent first allows a reduction in the benzodiazepine dose that is subsequently required (40). Ideally, medications for sedation should be slowly administered as boluses during 2-minute periods, each separated from the next by an interval of at least another 2 minutes (20). NARCOTIC ANALGESICS Meperidine Meperidine is a synthetic narcotic analgesic that is hepatically metabolized by N-demethylation. Because this process is less efficient in neonates, the half-life is longer than in older children and adults (46). With an IV dose of 1.0 to 1.5 mg/kg, meperidine demonstrates onset of action in 15 to 30 minutes, peak effect at 45 to 60 minutes, and a duration of action of 3 to 4 hours (47). Meperidine has a long and favorable experience in IV-s for pediatric endoscopy (6,19,48). In a study comparing the efficacy and safety in this setting of meperidine alone (in a dosage of 2 mg/kg) versus meperidine plus diazepam and diazepam alone, Bahal-O'Mara, et al. (48) actually found the meperidine single-agent regimen preferable, especially for patients less than 11 years of age. Side effects of meperidine are respiratory depression, nausea, vomiting, and dysphoria (49,50). It causes less histamine release and urticaria than morphine (6,51). Fentanyl Fentanyl is a synthetic opiate that is 80 to 150 times more potent than morphine (50–53). It is metabolized in the liver by dealkylation, hydroxylation, and amide hydrolysis to inactive metabolites (52). Plasma fentanyl concentrations are lower in infants and children than in adults when administered in similar gram per kilogram dosages. Yet, variation in pharmacokinetics with age, type of surgery, or underlying medical conditions (e.g., cyanotic congenital heart disease) make this agent's effects less predictable in pediatric patients (46,52). Fentanyl's high lipid solubility allows for quick penetration of the blood–brain barrier, resulting in a very rapid onset of action (<1 minute) and short duration of action (30–45 minutes) (51,53). These properties make it very attractive for use in conscious sedation for endoscopy (4). Quicker recovery times and lower concomitant doses of midazolam were reported with its use than with the use of meperidine with midazolam (20). Fentanyl can cause respiratory depression and apnea, especially when combined with other sedatives or in infants less than 3 months of age (51,53). Chest wall and glottic rigidity has been observed with rapid administration of fentanyl (51,53). This side effect is only partially reversed by naloxone and may even require intubation and assisted ventilation for management (47). Safe IV administration of fentanyl therefore requires slow titration of 0.5 to 1.0 μg/kg boluses, with several minutes' wait between dosages, and a maximum cumulative dose of 4 to 5 μg/kg in 1 hour (53,54). BENZODIAZEPINES Diazepam Diazepam's sedative and anxiolytic effects are caused by its interaction with the γ-aminobutyric acid (GABA) receptor complex and subsequent depression of the limbic amygdala and spinal afferent pathways (47,52). It is hepatically metabolized by hydroxylation and demethylation in the liver, both of which are reduced in the neonate, accounting for the longer half-life (approximately 30 hours) in premature and term infants compared with that in children (18 hours) (46). Because diazepam exhibits some degree of enterohepatic circulation, a second peak of the drug can occur 4 to 6 hours after administration, leading to re-sedation (40). In addition, one of diazepam's active metabolites has an elimination half-life of up to 72 hours (40). Propylene glycol is used as a carrier for intravenous diazepam and can lead to local thrombophlebitis and pain at injection sites (3). However, the incidence of phlebitis has been reported to be much lower with an emulsified preparation of diazepam in adults (55). Both diazepam and midazolam may produce paradoxical hyperactivity and respiratory depression, especially if used in combination with a narcotic (8,53). Gilger et al. (38) observed that a combination of diazepam and meperidine for pediatric upper endoscopic procedures was associated with an increased incidence of oxygen desaturation at various times during the procedure, in comparison with midazolam plus meperidine. Midazolam Midazolam is a short-acting benzodiazepine that is three to four times as potent as diazepam (46). It is very widely used because of its more rapid onset of action and shorter duration of effect compared with diazepam (9). Because it is in aqueous solution, no local irritation is usually seen after IV injection (46). At physiologic pH, the drug's ringed structure closes, increasing its lipophilic activity and allowing midazolam to readily cross the blood–brain barrier (46,52). This explains the agent's rapid onset of action in approximately 3 minutes, with maximal sedative effect by 5 minutes (56). Midazolam is also metabolized in the liver, with less than 1% of the drug appearing unchanged in the urine (46,52). Midazolam is somewhat unique among benzodiazepines in that its pharmacokinetics are dose related, with drug clearance increasing with increasing dosages (57). Tolia et al. (58) found that children receiving midazolam for EGD tended to metabolize and excrete the medication more rapidly than adults. Their patients, aged 6 to 18 years, demonstrated a mean elimination half-life of 47 minutes (56), which is lower than that reported in children by others (46,57) and significantly less than in adults (1.7–4.0 hours) (46). Because of this greater clearance of midazolam in children, larger weight-adjusted dosages may be required in pediatric patients than in adults to achieve similar levels and duration of sedation (22,56). An additional significant benefit of midazolam is the superior overall and anterograde amnesia it affords patients for their procedures (58,59). Although the sedative dose of midazolam commonly reported in children is up to 0.3 mg/kg, Gremse et al. (60) reported that a dose of more than 0.3 mg/kg was also well tolerated in conjunction with meperidine. Midazolam may also be administered by intramuscular, oral, intranasal, sublingual, and even rectal routes (53). A pediatric study comparing intranasal midazolam to IV administration for small bowel biopsy by capsule concluded that the IV route was preferable, because fewer doses of medication were needed to maintain sedation. Furthermore, intranasal midazolam caused substantial local discomfort (61). Oral midazolam tastes bitter, even with flavoring agents added (46,51). Disadvantages of midazolam include transient hypotension and vomiting, which may occur in up to 10% of patients (44,59). The shorter clinical half-life of the drug necessitates additional boluses for longer or complicated procedures. Finally, use of midazolam with fentanyl has been reported to cause respiratory arrest (62). REVERSAL AGENTS Naloxone Naloxone is a well-known opioid antagonist. This agent reverses both the sedative and analgesic properties of narcotics, leading to rebound pain and concomitant hypertension (41). Naloxone's brief clinical effects (less than 30 minutes in most children) may not outlast those of the narcotic being reversed, and the endoscopy team must therefore be watchful for relapsing sedation and respiratory depression (44,47). Nalmephene is a newer competitive opioid antagonist with a longer duration of action, lasting up to 3 to 4 hours (47). There is little experience with this agent in children. Flumazenil Flumazenil is a benzodiazepine antagonist, blocking the effect on the GABA receptor complex in the central nervous system (52). It has a rapid onset of action (within 30–60 seconds) with a mean elimination half-life of 53 minutes (40). Flumazenil has been shown to be safe and effective in reversing the effects of benzodiazepine-induced conscious sedation in children in several clinical situations, including endoscopy (63). However, Peters et al. (64) observed that after routine administration of this agent after sedation with diazepam and meperidine for EGD, recovery times were not hastened compared with placebo (64). It should be reserved for reversing excessive clinical sedation after benzodiazepine use, and its routine administration is not recommended. Adverse effects of flumazenil include nausea, vomiting, blurred vision, anxiety, and emotional liability. It can also precipitate seizures, especially in individuals with long-term benzodiazepine intake and in patients with tricyclic antidepressant overdose (47,52). The longer half-lives of midazolam and diazepam compared with that of flumazenil means that re-sedation can occur as the antagonistic effects of flumazenil wane (40,52). This is especially true for respiratory depression, which is reversed by flumazenil less reliably than the sedative effects (40,51). Therefore, children who require flumazenil should be monitored for an additional 1 to 2 hours after its administration (63). Overall, it is found that to produce adequate sedation for pediatric gastrointestinal endoscopic procedures, recommended dosage guidelines may need to be exceeded. Fortunately, adverse events occur only rarely under these circumstances (65). Conscious sedation should be performed only by individuals trained in pediatric resuscitation with appropriate equipment. Furthermore, these individuals should be able to handle oversedation and respiratory depression. POSTPROCEDURE PERIOD Monitoring Each patient must recovered from IV-s, just as with GA. Typically, all monitoring performed during a procedure should be continued for at least 30 minutes after a procedure. Vital signs must be stable for approximately 30 minutes after the procedure before discharge. No child should leave the hospital until becoming awake and alert. The older patient should be talking and show no new problems, such as persistent abdominal pain. Appropriate discharge criteria after a sedated procedure are summarized in Table 5.TABLE 5: Discharge criteria after sedationDischarge instructions should be reviewed with the patient and a responsible adult and a copy of the instructions furnished (Table 6). Finally, the patient must be accompanied home by an adult.TABLE 6: Postprocedure instructionsCONTROVERSIAL ISSUES IN SEDATION OF CHILDREN FOR GASTROINTESTINAL PROCEDURES Children cannot cooperate during procedures as can adults. Children's response to and recognition of anxiety change with age (66). For example, an infant more than 6 months of age is usually easy to sedate compared with the infant more than 6 months of age, in whom separation anxiety has developed. The presence of the parents during sedation of an infant more than 6 months of age may be beneficial. Psychological preparation of patients between the ages of 7 and 11 years is enhanced by allowing hands-on examination of the endoscope and monitoring equipment, taking advantage of the natural curiosity of this age group. Such efforts improve cooperation and relaxation with the sedation process. METABOLISM OF SEDATIVES IN CHILDREN The age of the child may be important in determining the appropriate sedation dosage. For example, the blood–brain barrier is still developing in the neonate. This results in a 20% to 100% greater penetration of narcotic and barbiturate medications through the blood–brain barrier (8,67). Hepatic drug metabolism for narcotics is also immature in infants less than 2 months of age. Thus, in neonates, the dosage of these medications are lower than in the adult to achieve the same level of sedation (68). In children up to 2.5 months of age, renal clearance is immature, requiring a lower dose of diazepam, which is cleared through the kidneys (8,65). Midazolam is metabolized and excreted much more rapidly in children than in adults, leading to the need for repeated doses of midazolam during a procedure (58). Interestingly, despite these physiologic and pharmacologic features of children that generally suggest lower sedation doses, children usually require higher doses of a sedative to achieve similar levels of sedation for a given procedure compared with an adult (60,65). SELECTING A SEDATION METHOD The highest ideals of medical practice require physicians not only to have excellent biomedical competence but also to deliver health care in a humanistic manner. This requires an individual approach to sedation for every patient. For example, high-risk patients can be identified before the procedure, by using the classification in Table 2. Children considered ASA classes 3, 4, and 5 would often be candidates for GA. Special situations, such as uncooperative patients, morbid obesity, sleep apnea, or known drug abuse, often dictate the use of GA as well. Moreover, if the child is terrified of needles, conscious sedation may not be easy to accomplish. Mahajan et al. (69) have shown that psychological preparation before endoscopy significantly decreases patient and parental anxiety. In their study, such preparation was associated with decreased sedative use. Most children are in ASA Class 1 or 2, and as such would be considered candidates for IV-s. Special circumstances, involving therapeutic procedures such as sclerotherapy or balloon dilation, and those involving large or sharp esophageal or gastric foreign bodies, usually require GA. Should Pediatric Gastroenterologists Administer the Sedation? Although it would be ideal for the endoscopist to have the luxury of having someone available who is solely responsible for administration of medication and concomitant monitoring of the patient, this is not always possible. Therefore, the pediatric endoscopist must be capable of providing appropriate sedation for endoscopic procedures and manage resuscitation if needed. CONCLUSIONS The use of endoscopy in children continues to increase. This increase has been fueled both by availability of trained pediatric gastroenterologists and the increasing application of diagnostic and therapeutic endoscopic techniques in children. The appropriate type of sedation is a matter of physician's judgment. This choice may be based on the characteristics of the individual patient, the type of procedure, and the knowledge and skills of the physician or may be dictated by practice trends within a community. Therefore the pediatric endoscopist must have two distinct areas of knowledge and skill: first, appropriate knowledge and training in the care of children and second, familiarity with the methods and agents available for sedation, including side effects. Advances in preprocedural psychologic interventions, focusing on behavioral and cognitive behavioral techniques, may help in reducing patient and parental anxiety and distress. Finally and perhaps most important, the pediatric gastroenterologist must be ever cognizant of the wide range of behavioral and maturational aspects unique to children to insure performance of safe and effective endoscopic procedures in this age group." @default.
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W2325323170 title "Sedation for Pediatric Endoscopic Procedures" @default.
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