Sedation for Pediatric Endoscopic Procedures

“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 μg/kg in 1 sedative and effects are by its with the and depression of the and It is hepatically metabolized by and in the of which are in the for the longer half-life 30 in and infants with that in children (46). Because diazepam degree of a peak of the drug can 4 to 6 hours after to (40). In of metabolites has an half-life of to hours (40). is used as a for intravenous diazepam and can to local and at (3). However, the of phlebitis has been reported to be much lower with an preparation of diazepam in adults diazepam and midazolam may and respiratory depression, especially if used in with a narcotic et al. observed that a of diazepam and meperidine for pediatric upper endoscopic procedures was associated with an of oxygen desaturation at times during the procedure, in with midazolam plus is a benzodiazepine that is three to times as potent as diazepam (46). It is very used because of its more rapid onset of action and duration of effect with diazepam Because it is in no local is usually after IV (46). physiologic the its and midazolam to the blood–brain barrier (46,52). This the agent's rapid onset of action in approximately 3 minutes, with sedative effect by minutes is also metabolized in the with less than of the drug in the (46,52). is in that its pharmacokinetics are dose with drug with dosages et al. found that children receiving midazolam for EGD to and the medication more than adults. aged 6 to 18 a half-life of minutes which is lower than that reported in children by and significantly less than in adults (46). Because of this greater of midazolam in children, dosages may be required in pediatric patients than in adults to achieve similar and duration of sedation An additional benefit of midazolam is the and anterograde amnesia it patients for their procedures the sedative dose of midazolam commonly reported in children is to mg/kg, et al. reported that a dose of more than was also in with may also be administered by and even A pediatric study comparing midazolam to IV administration for by that the IV was preferable, because doses of medication were to maintain sedation. midazolam local discomfort midazolam even with agents of midazolam and vomiting, which may in to of patients The clinical half-life of the drug additional boluses for longer or complicated procedures. use of midazolam with fentanyl has been reported to cause respiratory is a This agent the sedative and analgesic properties of to and concomitant brief clinical effects than 30 minutes in most may not those of the narcotic and the endoscopy team must therefore be for sedation and respiratory depression is a with a longer duration of action, to 3 to 4 hours (47). There is experience with this agent in children. is a benzodiazepine the effect on the in the (52). It has a rapid onset of action with a half-life of minutes (40). has been shown to be safe and effective in the effects of conscious sedation in children in several clinical including endoscopy However, et al. observed that after administration of this agent after sedation with diazepam and meperidine for recovery times were not with It should be for clinical sedation after benzodiazepine and its administration is not effects of nausea, vomiting, vision, anxiety, and It can also especially in with long-term benzodiazepine and in patients with The longer of midazolam and diazepam with that of that can as the effects of This is especially true for respiratory depression, which is reversed by less than the sedative effects children require should be for an additional 1 to 2 hours after its administration it is found that to adequate sedation for pediatric gastrointestinal endoscopic procedures, recommended dosage guidelines may to be adverse events only under these sedation should be performed only by in pediatric with appropriate these should be to oversedation and respiratory patient must from as with GA. all monitoring performed during a procedure should be continued for at least 30 minutes after a procedure. must be for approximately 30 minutes after the procedure before child should the until and The older patient should be and no problems, such as after a sedated procedure are in Table after should be reviewed with the patient and a adult and a of the (Table the patient must be accompanied by an SEDATION OF FOR during procedures as can adults. response to and recognition of anxiety with age For example, an more than 6 months of age is usually to sedate with the more than 6 months of age, in whom anxiety has The of the parents during sedation of an more than 6 months of age may be preparation of patients between the of 7 and 11 years is by of the endoscope and monitoring equipment, of the of this age cooperation and with the sedation OF The age of the child may be in the appropriate sedation For example, the blood–brain barrier is in the This in a to greater penetration of narcotic and medications the blood–brain barrier drug metabolism for narcotics is also in infants less than 2 months of age. in neonates, the dosage of these medications are lower than in the adult to achieve the level of sedation In children to months of age, renal is a lower dose of which is the is metabolized and much more in children than in to the for doses of midazolam during a procedure these physiologic and pharmacologic of children that suggest lower sedation children usually require higher doses of a sedative to achieve similar of sedation for a procedure with an adult A SEDATION The of medical require not only to have but also to in a This requires an individual approach to sedation for every patient. For example, patients can be before the procedure, by using the in Table 2. ASA classes and often be for GA. such as uncooperative obesity, apnea, or drug often the use of GA as if the child is of conscious sedation may not be to et al. have shown that psychological preparation before endoscopy significantly patient and anxiety. In their such preparation was associated with sedative Most children are in ASA 1 or and as such be for involving therapeutic procedures such as or and those involving or or gastric usually require GA. the it be ideal for the endoscopist to have the of available is for administration of medication and concomitant monitoring of the patient, this is not the pediatric endoscopist must be of providing appropriate sedation for endoscopic procedures and if needed. The use of endoscopy in children to This increase has been by of pediatric and the of diagnostic and therapeutic endoscopic techniques in children. The appropriate type of sedation is a matter of This choice may be based on the of the individual patient, the type of procedure, and the and of the physician or may be by a the pediatric endoscopist must have of and appropriate and training in the of children and with the and agents available for sedation, including side in preprocedural on behavioral and cognitive behavioral may in patient and anxiety and and most the pediatric gastroenterologist must be of the wide of behavioral and maturational to children to performance of safe and effective endoscopic procedures in this age