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Intravenous sedation in pediatric upper gastrointestinal endoscopy
0016-5107/95/4202-015653.00 + 0 GASTROINTESTINAL ENDOSCOPY Copyright © 1995 by the American Society for Gastrointestinal Endoscopy
Intravenous sedation in pediatric upper gastrointestinal endoscopy Emil Chuang, MD, William J. Wenner, Jr., MD, David A. Piccoli, MD Steven M. Altschuler, MD, Chris A. Liacouras, MD Phi/ade/phia, Pennsylvania To assess the safety and efficacy of intravenous sedation in pediatric upper endoscopy, all elective outpatient procedures performed during a 2-year period (January 1, 1991 through December 31, 1992) were retrospectively reviewed. Of 614 children, 553 received intravenous meperidine and midazolam; 61 received fentanyl and midazolam. The mean dose of meperidine was 1.5 ± 0.7 mg/kg and of fentanyl 0.0031 ± 0.0014 mg/kg. Less midazolam was needed for children receiving fentanyl than for those receiving meperidine (0.05 ± 0.03 mg/kg versus 0.08 ± 0.05 mg/kg, p < 002). Recovery time (minutes) was shorter for those receiving fentanyl (74.7 ± 22.8 versus 95.1 ± 23.0, p < .003). Side effects occurred in 117 patients (19.1%), of which the majority were mild (83%); all were transient with no residual sequelae. Inability to complete the procedure occurred in fewer than 1%. We conclude that both combinations of medication are safe and effective for children of all ages. The use of fentanyl/midazolam results in a shorter recovery time and a lower dose of midazolam. (Gastrointest Endosc 1995;42:156-60.)
There are few descriptions of the indications, pharmacology, and safety of sedation in pediatric esophagogastroduodenoscopy (EGD). The mode of sedation and choice of medication vary among pediatric gastroenterologists. Although some physicians perform all EGDs under general anesthesia, an increasing number of pediatric gastroenterologists are now using intravenous (IV) sedation, which can be given to achieve either conscious or deep sedation. Conscious sedation can be defined as "a medically controlled state of depressed consciousness that allows protective reflexes to be maintained, does not interfere with the patient's ability to maintain a patent airway independently and continuously, and permits appropriate response by the patient to physical stimulation or verbal command. "1, u Deep sedation can be defined as Received May 3, 1994. For revision August 24, 1994. Accepted October 20, 1994. From the Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania Medical School, Philadelphia, Pennsylvania. Reprint requests: Chris A. Liacouras, MD, The Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA 19104. 37/1/61390 156
GASTROINTESTINAL ENDOSCOPY
"a medically controlled state of depressed consciousness or unconsciousness from which the patient is not easily aroused. "1, 2 Most of the experience in pediatric IV sedation has been acquired during dental procedures, cardiac catheterizations, and general ward procedures. 38 In the adult population, the efficacy and safety of IV conscious sedation for EGD has been well documented. 9"11 Although these experiences are of value as a guideline, caution may be needed in applying the results to pediatric EGD because pediatric UGI endoscopy is different from other pediatric procedures in nature and duration. Some investigators argue that most pediatric EGDs cannot be performed with conscious sedation. In a recent editorial, Hassal112 advocated against the use of IV sedation in pediatric procedures. He argued that conscious sedation typically results in unsafe, prolonged, or aborted procedures; endoscopic examinations of poor quality; missed diagnoses; fearful children and parents, and frustrated health care professionals. This is contrary to the experience at The Children's Hospital of Philadelphia, where the majority of elective EGDs are performed under intravenous sedation. Although conscious sedation is easily deVOLUME42, NO. 2, 1995
Table 1. Comparison of medication doses in each group by age
200
Pafientage <1 year
100
7
50
0
<1
1
2
3
4
5
6
7
8 9 10 A g e (years)
11
12
13
14
t5
16
17 >18
Figure 1. Age distribution of study patients. fined in school-age children and adolescents, it can become difficult to define in children under 3 years of age; however, safe and effective intravenous sedation can be safely achieved in preschool-age children without the loss of protective reflexes and without additional risk even though the precise definition of conscious sedation m a y not be met. The following study evaluates the safety and efficacy of intravenous s e d a t i o n for all p a t i e n t s w h o u n d e r w e n t elective outp a t i e n t E G D d u r i n g a 2 - y e a r period.
METHODS All elective pediatric outpatient EGDs performed with conscious sedation during a 2-year period were reviewed. Records were analyzed according to two parameters: patient age (infants <1 year of age or children <1 year of age) and medications administered (meperidine/midazolam or fentanyl/midazolam). Endoscopy and hospital records were analyzed for recovery time, age of patient, medications given, and side effects of sedation. Side effects of sedation were categorized as respiratory arrest, hypotension, bradycardia (decrease in heart rate >20%), hives, facial flushing, anaphylaxis, inability to achieve sedation, or oxygen desaturation. Oxygen desaturation, determined by pulse oximetry, was further defined as transient (saturation <93% recovering to >95% within 15 seconds) or prolonged (saturation <93% for >15 seconds). Patients were sedated with either midazolam (Versed) and meperidine (Demerol) or midazolam and fentanyl (Sublimaze). Fentanyl was first approved for hospital use for conscious sedation in July 1992. The choice of sedation was made by the endoscopist. All medications were given intravenously and titrated to achieve a depressed level of consciousness, characterized by (1) sleepiness with continued responsiveness to commands; (2) slurred speech, drooping eyelids, or nonsensical speech; (3) no loss of protective reflexes or respiratory depression requiring assisted ventilation. Intravenous medications were given according to standards previously approved by the Pediatric and Anesthesiology Standards Committee at The Children's Hospital of Philadelphia. The dosing guidelines are as follows: (1) midazolam--initial dose 0.05 to 0.1 mg/kg (maximum 2.5 mg), followed by titrating doses of 0.025 to 0.05 mg/kg and net exceeding a total dose of 0.4 mg/kg or 10 mg; (2) meperidine--initial dose 0.5 to 1.0 mg/kg (maximum 50 nag), V O L U M E 42, NO. 2, 1995
>1 year
p Value
Fentanyl group (n = 15) (n = 46) Midazolam (mg/kg) 0.01 _ 0.01 0.06 __-0.03 <.001 Fentanyl (mg/kg) 0.0030 _+0.00067 0.0031 _+0.0015 NS Meperidine group (n = 135) (n = 418) Midazolam (mg/kg) 0.11 _+0.05 0.08 ± 0.04 <.001 Meperidine (mg/kg) 1.54 _+0.63 1.53 ± 0.72 NS N, number of patients. followed by titrating doses of 0.25 to 1.0 mg/kg and not exceeding a total dose of 4 mg/kg or 150 mg; (3) fentanyl--initial dose 0.001 mg/kg (maximum 0.050 mg), followed by titrating doses of 0.001 mg/kg and not exceeding a total dose of 0.006 mg/kg or 0.200 mg. Titrating doses of all medications were given for 2-minute periods at least 2 minutes apart in order to judge the patient's level of sedation. The amount of sedation was determined by the endoscopist and was titrated to achieve a depressed level of consciousness as described above. Patients initially presented to t h e Day Medicine Unit, where baseline vital signs were taken and an IV line was placed. All patients were monitored by a dedicated nurse; continuous pulse oximetry (Nellcor pulse oximeter, Nellcor Inc., Heyward, Calif.) and noninvasive measurement of heart rate and blood pressure (Dinamapp vital signs monitor, Critikon, Tampa, Fla.) were performed. Topical Hurricaine spray was utilized in all patients older than 5 years of age. Vital signs were recorded every 3 minutes. Supplemental oxygen was given for all prolonged desaturation events (see above). Recovery time was defined as the time elapsed between the end of the procedure and discharge from the recovery unit. The following criteria had to be met for discharge: (1) patients had to be awake and alert and able to follow simple commands; (2) patients had to be able to tolerate at least 4 oz of oral fluid without emesis; (3) patients' vital signs were stable.
Statistical analysis All values are expressed as mean -+ I standard deviation. Mean values of medication doses and recovery time were compared by Student's paired t test. Procedural complications were compared by the chi-squared test and Student's paired t test for independent samples. Values for p of less than .05 were considered significant.
RESULTS B e t w e e n J a n u a r y 1, 1991 a n d D e c e m b e r 31, 1992, 710 elective o u t p a t i e n t E G D s w e r e p e r f o r m e d , of w h i c h full a n d complete i n f o r m a t i o n w a s a v a i l a b l e in 614 (86.5%). T h e age d i s t r i b u t i o n of p a t i e n t s studied is s h o w n in F i g u r e 1. A c o m b i n a t i o n of m e p e r i d i n e a n d m i d a z o l a m w a s given to 553 p a t i e n t s ( m e p e r i d i n e group), a n d 61 received f e n t a n y l a n d m i d a z o l a m (fentanyl group). GASTROINTESTINAL ENDOSCOPY
157
Table 2. Comparison of number of intraoperative complications of EGD in meperidine and fentanyl groups by age Meperidine
Fentanyl
<1 year >1 year <1 year >1 year (n=135) (n=418) pvalue (n=15) (n=46) p value Oxygendesaturation, transient* 9 40 NS 1 8 NS Oxygendesaturation, prolongedt 10 6 <.002 2 1 NS Facial flushing 13 16 <.01 3 3 <.01 Hives 6 26 NS 0 1 NS Failed EGD 1 5 NS 0 0 NS N, numberof patients. *No supplementaloxygenrequired, desaturation<15 seconds. ?Supplemental oxygenrequired, desaturation>15 seconds. The dose of midazolam per kilogram of body weight was 37.5% less for the fentanyl group t h a n for the meperidine group (p < .002). Recovery time was 21% shorter for the fentanyl group t h a n for the meperidine group (74.7 -+ 22.8 minutes versus 91.1 _+ 23.0 minutes, p < .003). Age of the patient had a significant effect on the total dose of midazolam. In the meperidine group, the dose ofmidazolam given to infants less than 1 year of age was 27.2% less than the dose given to children more t h a n 1 year of age (p < .001). In the fentanyl group, the dose ofmidazolam given to infants less t h a n 1 year of age was 83% less than the dose given to children more t h a n 1 year of age (p < .001) (Table 1). The doses of meperidine and fentanyl were not significantly different between age groups.
Side effects One hundred fifty-one side effects of sedation were noted in 117 (19.1%) patients (Table 2). The majority (83%) were minor (transient oxygen desaturation, facial flushing, and hives). Prolonged oxygen desaturation occurred in 3.1% of all patients. Inadequate sedation resulting in incomplete endoscopy occurred in fewer than 1% of all patients. Of the 33 patients in whom hives developed, 23 received diphenhydramine hydrochloride (Benadryl). Naloxone was given to 12 of the 19 who had prolonged oxygen desaturation. All patients with transient oxygen desaturation responded to supplemental oxygen. Assisted ventilation was not required. Flumazenil was given to one patient to reverse a paradoxical response to midazolam. Respiratory arrest, hypotension, significant bradycardia, cardiac arrhythmias, or anaphylactic reactions were not observed. No significant difference was noted in side effects between the meperidine group and the fentanyl group; however, the incidence of hives and failed EGDs was higher in the meperidine group. Oxygen desaturation and facial flushing were more frequent in the fentanyl group, but neither difference was significant. Pro158 GASTROINTESTINAL E N D O S C O P Y
longed oxygen desaturation occurred more often in infants less than 1 year of age who received meperidine/midazolam than in children greater t h a n 1 year in the same medication group (p < .002) (Table 2). No significant difference was found in dose of medication (midazolam, meperidine, or fentanyt) between children who developed significant side effects (prolonged oxygen desaturation, hives, facial flushing) and children who had no side effects (paired t test).
DISCUSSION Intravenous sedation for adult UGI endoscopy has been shown to be both effective and safe. 13 Currently, most gastroenterologists use an opioid and benzodiazepine combination for sedation in adult patients. 14 The use of such intravenous sedation for pediatric patients undergoing EGD, although debated, has increased because of improved training and quality assurance, a perceived increased incidence of pediatric gastrointestinal disorders, and the high costs associated with general anesthesia. 15 During the past 5 years, differences in the dose of medication required for IV sedation in pediatric EGD has been observed as compared with the dose of medication required to sedate adults. Andrus et al. 16 reported t h a t in adults the mean total dose of meperidine was 0.8 mg/kg. This pediatric experience found a total dose to be 1.5 z 0.7 mg/kg. Bell et al. 17 reported a mean total dose of midazolam for adults of I rag; this pediatric experience found an average total dose of midazolam to be 1.7 ~- 0.8 mg. The above differences may be explained in part by anxiety or by the increased metabolism and excretion of drugs in children. Tolia et al. 1° prospectively evaluated the pharmacokinetics of midazolam in children undergoing UGI endoscopy and concluded t h a t children metabolize and excrete midazolam more rapidly than adults. Transient side effects of sedation were seen in 19.1% of all patients. Transient oxygen desaturation occurred in 9.6% of these patients, which is less than t h a t reported recently by Gilger et al. 18 These events VOLUME 42, NO. 2, 1995
were quickly and completely reversed and did not impact on the procedure or the patient. Potentially serious side effects (oxygen desaturation lasting more t h a n 15 seconds) were seen in 3.1%; all responded to oxygen supplementation or naloxone. In this study, oxygen was immediately available but not routinely administered. However, the routine use of oxygen may have significant benefits, especially in children under 1 year of age, and is recommended by some endoscopists. In comparison, The American Society for Gastrointestinal Endoscopy reported the complications of endoscopy in a collaborative study of 21,000 adults. 13 Severe cardiorespiratory events defined by death or need for a medical or surgical intervention occurred in fewer t h a n 1% of procedures (114 events, 7 deaths). Naloxone was needed in 14% of procedures, compared to fewer t h a n 2% in our study. Unfortunately, the adult study did not report mild side effects, such as transient oxygen desaturation or rash. Although we report a 19% complication rate, we were extremely strict in our definition of side effects. If we had used the collaborative study definition of side effects, we would have had no complications. Some pediatric endoscopists believe t h a t performing UGI endoscopy under IV sedation m a y result in an unacceptable failure rate and is unsafe when compared with general anesthesia. 12, 19 Yaster et a19 ° reported a case of respiratory arrest in a 14-month-old child who received midazolam and fentanyl. As reported, the child received a midazolam bolus of 0.11 mg/kg followed by three boluses of fentanyl in doses of 0.002 mg/kg. Although in total this dose may have been appropriate, we believe t h a t complications occur when midazolam, meperidine, and fentanyl are given too rapidly. In our institution, we administer all medication with flowing intravenous fluid. As defined in our methods, each bolus of medication is given during a 2-minute period. Periods are spaced at least 2 minutes apart. Additionally, we limit the dose of each bolus to midazolam 0.1 mg/kg, meperidine 1 mg/kg, and fentanyl 0.001 mg/kg. Although time-consuming, we believe t h a t our standards allow the use of large but adequate doses of medication, resulting in safe and comfortable procedures for children. To achieve acceptable results with IV sedation, an experienced endoscopist trained in pediatric endoscopy and administration of IV sedation is required. Also required are continuous monitoring of vital signs and oxygen saturation, adequate endoscopy personnel (a nurse to observe the patient, a technician, and individuals trained in the use of pediatric ACLS), adequate equipment (nasogastric suction, pediatric laryngoscopes, and Ambu bags), and an adequate facility where the patient can be observed after completion of the procedure. VOLUME 42, NO. 2, 1995
The use of IV sedation in pediatric UGI endoscopy offers a safe, effective, and less costly alternative to general anesthesia. In this study, successful sedation was achieved in 99% of all elective procedures. Currently, some investigators argue t h a t pediatric endoscopy cannot be performed with IV medication unless deep sedation is achieved. In the above study, in all but five children older t h a n 4 years, a safe EGD was performed under the guidelines of conscious sedation (protection of reflexes and ability to follow commands). In the children aged 4 years or less, a response to voice commands was difficult to interpret, and one could therefore argue t h a t deep sedation may have been used; however, in all cases the gag reflex remained intact and every patient continued to be aroused on insertion of the endoscope. On the other hand, general anesthesia should be used for specific patients. At our institution, we utilize general anesthesia for all patients who are at increased risk for cardiorespiratory complications, who are profoundly mentally retarded, who require therapeutic endoscopy (such as removal of foreign body, balloon dilation, or sclerotherapy), or who are exceedingly anxious or previously failed IV sedation. Although investigators may continue to argue that IV sedation for pediatric endoscopy must utilize deep sedation, this study demonstrates t h a t excellent results can be achieved in a large number of pediatric patients of all ages while adhering to the definition of conscious sedation. It also demonstrates t h a t both meperidine/midazolam and fentanyl/midazolam are safe and effective; however, the results with fentanyl show a significantly shorter recovery time, suggesting that it is associated with fewer side effects when used in combination with midazolam and may be the drug of choice for future endoscopic procedures. REFERENCES
1. AmericanAcademyof Pediatrics Committeeon Drugs: guidelines for monitoring and management of pediatric patients during and after sedationfor diagnosticand therapeuticprocedures. Pediatrics 1992;89:1110-5. 2. BenarochLM, Rudolph CD. Introductionto pediatric esophagogastroduodenoscopyand enteroscopy. Gastrointest Endosc 1994;4:121-42. 3. CookBA, Bass JW, NomizuS, AlexanderME. Sedationofchildren fortechnicalprocedures:current standard ofpractice. Clin Pediatr 1992;31:137-42. 4. Smith C, Rowe RD, Vlad P. Sedation of children for cardiac catheterizationwith ataracticmixture. CanadianAnesthetists SocietyJournal 1985;5:35-43. 5. Waggoner WF. Conscious sedation in predoctoral pediatric dentistry programs. J Dent Educ 1986;50:225-9. 6. Guidelines for the elective use of conscious sedation, deep sedation, and general anesthesia in pediatric patients. Committee on Drugs. Section on anesthesiology.Pediatrics 1985; 76:317-21. 7. ChanLY, Tan CL. Use of intravenous midazolamfor sedation in children undergoingward procedures. Journal of the Singapore Paediatric Society1992;34:30-3. 8. Barr EB, Wynn RL. IV sedation in pediatric dentistry: an GASTROINTESTINAL ENDOSCOPY
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9.
10. 11.
12. 13.
14.
alternative to general anesthesia. Pediatric Dentistry 1992;14: 251-5. Bahal-O'Mara N, Nahata MC, Murray RD, et al. Efficacy ofdiazepam and meperidine in ambulatory pediatric patients undergoing endoscopy: a randomized, double-blind trial. J Pediatr Gastroenterol Nutr 1993;16:387-92. Tolia V, Fleming SL, Kauffman RE. Randomized, double-blind trial of midazolam and diazepam for endoscopic sedation in children. Dev Pharamcol Ther 1990;14:141-7. Nahata MC, Murray RD, Zingare]li J, Li BU, McClung HJ, Lininger B. Efficacy and safety of diazepam and meperidine combination for pediatric gastrointestinal procedures. J Pediatr Gastroenterol Nutr 1990;10:335-8. Hassall E. Should pediatric gastroenterologists be i.v. drug users? J Pediatr Gastroenterol Nutr 1993;16:387-92. Arrowsmith JB, Gerstman BB, Fleischer DE, Benjamin SB. Results from the American Society for Gastrointestinal Endoscopy/U.S. Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy. Gastrointest Endosc 1991;37:421-7. Deneshmend TK, Bell GD, Logan RF. Sedation for upper endoscopy: results of a nationwide survey. Gut 1991;32:12-5.
15. Kato S, Nakagawa H, Harada Y, et al. A clinical study &upper gastrointestinal endoscopy in Japanese children. Acta Paediatr Jpn 1991;33:36-42. 16. Andrus CH, Dean PA, Ponsky JL. Evaluation of safe, effective intravenous sedation for utilization in endoscopic procedures. Surg Endosc 1990;4:179-83. 17. Bell GD, Spickett GP, Reeve PA, Mordan A, Logan RF. Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient. Br J Clin Pharmacol 1987;23:241-3. 18. Gilger MA, Jeiven SD, Barrish JO, McCarroll LR. Oxygen desaturation and cardiac arrhythmias in children during esophagogastroduodenoscopyusing conscious sedation. Gastrointest Endosc 1993;39:392-5. 19. Ellett ML. General anesthesia: an alternative to sedation for pediatric endoscopic procedures. Gastroenterology Nursing 1991;13:166-8. 20. Yaster M, Nichols DG, Deshpande JK, Wetzel RC. Midazolamfentanyl intravenous sedation in children: case report of respiratory arrest. Pediatrics 1990;86:463-7.
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160 G A S T R O I N T E S T I N A L E N D O S C O P Y
V O L U M E 42, NO. 2, 1995
Intravenous sedation in pediatric upper gastrointestinal endoscopy Emil Chuang, MD, William J. Wenner, Jr., MD, David A. Piccoli, MD Steven M. Altschuler, MD, Chris A. Liacouras, MD Phi/ade/phia, Pennsylvania To assess the safety and efficacy of intravenous sedation in pediatric upper endoscopy, all elective outpatient procedures performed during a 2-year period (January 1, 1991 through December 31, 1992) were retrospectively reviewed. Of 614 children, 553 received intravenous meperidine and midazolam; 61 received fentanyl and midazolam. The mean dose of meperidine was 1.5 ± 0.7 mg/kg and of fentanyl 0.0031 ± 0.0014 mg/kg. Less midazolam was needed for children receiving fentanyl than for those receiving meperidine (0.05 ± 0.03 mg/kg versus 0.08 ± 0.05 mg/kg, p < 002). Recovery time (minutes) was shorter for those receiving fentanyl (74.7 ± 22.8 versus 95.1 ± 23.0, p < .003). Side effects occurred in 117 patients (19.1%), of which the majority were mild (83%); all were transient with no residual sequelae. Inability to complete the procedure occurred in fewer than 1%. We conclude that both combinations of medication are safe and effective for children of all ages. The use of fentanyl/midazolam results in a shorter recovery time and a lower dose of midazolam. (Gastrointest Endosc 1995;42:156-60.)
There are few descriptions of the indications, pharmacology, and safety of sedation in pediatric esophagogastroduodenoscopy (EGD). The mode of sedation and choice of medication vary among pediatric gastroenterologists. Although some physicians perform all EGDs under general anesthesia, an increasing number of pediatric gastroenterologists are now using intravenous (IV) sedation, which can be given to achieve either conscious or deep sedation. Conscious sedation can be defined as "a medically controlled state of depressed consciousness that allows protective reflexes to be maintained, does not interfere with the patient's ability to maintain a patent airway independently and continuously, and permits appropriate response by the patient to physical stimulation or verbal command. "1, u Deep sedation can be defined as Received May 3, 1994. For revision August 24, 1994. Accepted October 20, 1994. From the Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania Medical School, Philadelphia, Pennsylvania. Reprint requests: Chris A. Liacouras, MD, The Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA 19104. 37/1/61390 156
GASTROINTESTINAL ENDOSCOPY
"a medically controlled state of depressed consciousness or unconsciousness from which the patient is not easily aroused. "1, 2 Most of the experience in pediatric IV sedation has been acquired during dental procedures, cardiac catheterizations, and general ward procedures. 38 In the adult population, the efficacy and safety of IV conscious sedation for EGD has been well documented. 9"11 Although these experiences are of value as a guideline, caution may be needed in applying the results to pediatric EGD because pediatric UGI endoscopy is different from other pediatric procedures in nature and duration. Some investigators argue that most pediatric EGDs cannot be performed with conscious sedation. In a recent editorial, Hassal112 advocated against the use of IV sedation in pediatric procedures. He argued that conscious sedation typically results in unsafe, prolonged, or aborted procedures; endoscopic examinations of poor quality; missed diagnoses; fearful children and parents, and frustrated health care professionals. This is contrary to the experience at The Children's Hospital of Philadelphia, where the majority of elective EGDs are performed under intravenous sedation. Although conscious sedation is easily deVOLUME42, NO. 2, 1995
Table 1. Comparison of medication doses in each group by age
200
Pafientage <1 year
100
7
50
0
<1
1
2
3
4
5
6
7
8 9 10 A g e (years)
11
12
13
14
t5
16
17 >18
Figure 1. Age distribution of study patients. fined in school-age children and adolescents, it can become difficult to define in children under 3 years of age; however, safe and effective intravenous sedation can be safely achieved in preschool-age children without the loss of protective reflexes and without additional risk even though the precise definition of conscious sedation m a y not be met. The following study evaluates the safety and efficacy of intravenous s e d a t i o n for all p a t i e n t s w h o u n d e r w e n t elective outp a t i e n t E G D d u r i n g a 2 - y e a r period.
METHODS All elective pediatric outpatient EGDs performed with conscious sedation during a 2-year period were reviewed. Records were analyzed according to two parameters: patient age (infants <1 year of age or children <1 year of age) and medications administered (meperidine/midazolam or fentanyl/midazolam). Endoscopy and hospital records were analyzed for recovery time, age of patient, medications given, and side effects of sedation. Side effects of sedation were categorized as respiratory arrest, hypotension, bradycardia (decrease in heart rate >20%), hives, facial flushing, anaphylaxis, inability to achieve sedation, or oxygen desaturation. Oxygen desaturation, determined by pulse oximetry, was further defined as transient (saturation <93% recovering to >95% within 15 seconds) or prolonged (saturation <93% for >15 seconds). Patients were sedated with either midazolam (Versed) and meperidine (Demerol) or midazolam and fentanyl (Sublimaze). Fentanyl was first approved for hospital use for conscious sedation in July 1992. The choice of sedation was made by the endoscopist. All medications were given intravenously and titrated to achieve a depressed level of consciousness, characterized by (1) sleepiness with continued responsiveness to commands; (2) slurred speech, drooping eyelids, or nonsensical speech; (3) no loss of protective reflexes or respiratory depression requiring assisted ventilation. Intravenous medications were given according to standards previously approved by the Pediatric and Anesthesiology Standards Committee at The Children's Hospital of Philadelphia. The dosing guidelines are as follows: (1) midazolam--initial dose 0.05 to 0.1 mg/kg (maximum 2.5 mg), followed by titrating doses of 0.025 to 0.05 mg/kg and net exceeding a total dose of 0.4 mg/kg or 10 mg; (2) meperidine--initial dose 0.5 to 1.0 mg/kg (maximum 50 nag), V O L U M E 42, NO. 2, 1995
>1 year
p Value
Fentanyl group (n = 15) (n = 46) Midazolam (mg/kg) 0.01 _ 0.01 0.06 __-0.03 <.001 Fentanyl (mg/kg) 0.0030 _+0.00067 0.0031 _+0.0015 NS Meperidine group (n = 135) (n = 418) Midazolam (mg/kg) 0.11 _+0.05 0.08 ± 0.04 <.001 Meperidine (mg/kg) 1.54 _+0.63 1.53 ± 0.72 NS N, number of patients. followed by titrating doses of 0.25 to 1.0 mg/kg and not exceeding a total dose of 4 mg/kg or 150 mg; (3) fentanyl--initial dose 0.001 mg/kg (maximum 0.050 mg), followed by titrating doses of 0.001 mg/kg and not exceeding a total dose of 0.006 mg/kg or 0.200 mg. Titrating doses of all medications were given for 2-minute periods at least 2 minutes apart in order to judge the patient's level of sedation. The amount of sedation was determined by the endoscopist and was titrated to achieve a depressed level of consciousness as described above. Patients initially presented to t h e Day Medicine Unit, where baseline vital signs were taken and an IV line was placed. All patients were monitored by a dedicated nurse; continuous pulse oximetry (Nellcor pulse oximeter, Nellcor Inc., Heyward, Calif.) and noninvasive measurement of heart rate and blood pressure (Dinamapp vital signs monitor, Critikon, Tampa, Fla.) were performed. Topical Hurricaine spray was utilized in all patients older than 5 years of age. Vital signs were recorded every 3 minutes. Supplemental oxygen was given for all prolonged desaturation events (see above). Recovery time was defined as the time elapsed between the end of the procedure and discharge from the recovery unit. The following criteria had to be met for discharge: (1) patients had to be awake and alert and able to follow simple commands; (2) patients had to be able to tolerate at least 4 oz of oral fluid without emesis; (3) patients' vital signs were stable.
Statistical analysis All values are expressed as mean -+ I standard deviation. Mean values of medication doses and recovery time were compared by Student's paired t test. Procedural complications were compared by the chi-squared test and Student's paired t test for independent samples. Values for p of less than .05 were considered significant.
RESULTS B e t w e e n J a n u a r y 1, 1991 a n d D e c e m b e r 31, 1992, 710 elective o u t p a t i e n t E G D s w e r e p e r f o r m e d , of w h i c h full a n d complete i n f o r m a t i o n w a s a v a i l a b l e in 614 (86.5%). T h e age d i s t r i b u t i o n of p a t i e n t s studied is s h o w n in F i g u r e 1. A c o m b i n a t i o n of m e p e r i d i n e a n d m i d a z o l a m w a s given to 553 p a t i e n t s ( m e p e r i d i n e group), a n d 61 received f e n t a n y l a n d m i d a z o l a m (fentanyl group). GASTROINTESTINAL ENDOSCOPY
157
Table 2. Comparison of number of intraoperative complications of EGD in meperidine and fentanyl groups by age Meperidine
Fentanyl
<1 year >1 year <1 year >1 year (n=135) (n=418) pvalue (n=15) (n=46) p value Oxygendesaturation, transient* 9 40 NS 1 8 NS Oxygendesaturation, prolongedt 10 6 <.002 2 1 NS Facial flushing 13 16 <.01 3 3 <.01 Hives 6 26 NS 0 1 NS Failed EGD 1 5 NS 0 0 NS N, numberof patients. *No supplementaloxygenrequired, desaturation<15 seconds. ?Supplemental oxygenrequired, desaturation>15 seconds. The dose of midazolam per kilogram of body weight was 37.5% less for the fentanyl group t h a n for the meperidine group (p < .002). Recovery time was 21% shorter for the fentanyl group t h a n for the meperidine group (74.7 -+ 22.8 minutes versus 91.1 _+ 23.0 minutes, p < .003). Age of the patient had a significant effect on the total dose of midazolam. In the meperidine group, the dose ofmidazolam given to infants less than 1 year of age was 27.2% less than the dose given to children more t h a n 1 year of age (p < .001). In the fentanyl group, the dose ofmidazolam given to infants less t h a n 1 year of age was 83% less than the dose given to children more t h a n 1 year of age (p < .001) (Table 1). The doses of meperidine and fentanyl were not significantly different between age groups.
Side effects One hundred fifty-one side effects of sedation were noted in 117 (19.1%) patients (Table 2). The majority (83%) were minor (transient oxygen desaturation, facial flushing, and hives). Prolonged oxygen desaturation occurred in 3.1% of all patients. Inadequate sedation resulting in incomplete endoscopy occurred in fewer than 1% of all patients. Of the 33 patients in whom hives developed, 23 received diphenhydramine hydrochloride (Benadryl). Naloxone was given to 12 of the 19 who had prolonged oxygen desaturation. All patients with transient oxygen desaturation responded to supplemental oxygen. Assisted ventilation was not required. Flumazenil was given to one patient to reverse a paradoxical response to midazolam. Respiratory arrest, hypotension, significant bradycardia, cardiac arrhythmias, or anaphylactic reactions were not observed. No significant difference was noted in side effects between the meperidine group and the fentanyl group; however, the incidence of hives and failed EGDs was higher in the meperidine group. Oxygen desaturation and facial flushing were more frequent in the fentanyl group, but neither difference was significant. Pro158 GASTROINTESTINAL E N D O S C O P Y
longed oxygen desaturation occurred more often in infants less than 1 year of age who received meperidine/midazolam than in children greater t h a n 1 year in the same medication group (p < .002) (Table 2). No significant difference was found in dose of medication (midazolam, meperidine, or fentanyt) between children who developed significant side effects (prolonged oxygen desaturation, hives, facial flushing) and children who had no side effects (paired t test).
DISCUSSION Intravenous sedation for adult UGI endoscopy has been shown to be both effective and safe. 13 Currently, most gastroenterologists use an opioid and benzodiazepine combination for sedation in adult patients. 14 The use of such intravenous sedation for pediatric patients undergoing EGD, although debated, has increased because of improved training and quality assurance, a perceived increased incidence of pediatric gastrointestinal disorders, and the high costs associated with general anesthesia. 15 During the past 5 years, differences in the dose of medication required for IV sedation in pediatric EGD has been observed as compared with the dose of medication required to sedate adults. Andrus et al. 16 reported t h a t in adults the mean total dose of meperidine was 0.8 mg/kg. This pediatric experience found a total dose to be 1.5 z 0.7 mg/kg. Bell et al. 17 reported a mean total dose of midazolam for adults of I rag; this pediatric experience found an average total dose of midazolam to be 1.7 ~- 0.8 mg. The above differences may be explained in part by anxiety or by the increased metabolism and excretion of drugs in children. Tolia et al. 1° prospectively evaluated the pharmacokinetics of midazolam in children undergoing UGI endoscopy and concluded t h a t children metabolize and excrete midazolam more rapidly than adults. Transient side effects of sedation were seen in 19.1% of all patients. Transient oxygen desaturation occurred in 9.6% of these patients, which is less than t h a t reported recently by Gilger et al. 18 These events VOLUME 42, NO. 2, 1995
were quickly and completely reversed and did not impact on the procedure or the patient. Potentially serious side effects (oxygen desaturation lasting more t h a n 15 seconds) were seen in 3.1%; all responded to oxygen supplementation or naloxone. In this study, oxygen was immediately available but not routinely administered. However, the routine use of oxygen may have significant benefits, especially in children under 1 year of age, and is recommended by some endoscopists. In comparison, The American Society for Gastrointestinal Endoscopy reported the complications of endoscopy in a collaborative study of 21,000 adults. 13 Severe cardiorespiratory events defined by death or need for a medical or surgical intervention occurred in fewer t h a n 1% of procedures (114 events, 7 deaths). Naloxone was needed in 14% of procedures, compared to fewer t h a n 2% in our study. Unfortunately, the adult study did not report mild side effects, such as transient oxygen desaturation or rash. Although we report a 19% complication rate, we were extremely strict in our definition of side effects. If we had used the collaborative study definition of side effects, we would have had no complications. Some pediatric endoscopists believe t h a t performing UGI endoscopy under IV sedation m a y result in an unacceptable failure rate and is unsafe when compared with general anesthesia. 12, 19 Yaster et a19 ° reported a case of respiratory arrest in a 14-month-old child who received midazolam and fentanyl. As reported, the child received a midazolam bolus of 0.11 mg/kg followed by three boluses of fentanyl in doses of 0.002 mg/kg. Although in total this dose may have been appropriate, we believe t h a t complications occur when midazolam, meperidine, and fentanyl are given too rapidly. In our institution, we administer all medication with flowing intravenous fluid. As defined in our methods, each bolus of medication is given during a 2-minute period. Periods are spaced at least 2 minutes apart. Additionally, we limit the dose of each bolus to midazolam 0.1 mg/kg, meperidine 1 mg/kg, and fentanyl 0.001 mg/kg. Although time-consuming, we believe t h a t our standards allow the use of large but adequate doses of medication, resulting in safe and comfortable procedures for children. To achieve acceptable results with IV sedation, an experienced endoscopist trained in pediatric endoscopy and administration of IV sedation is required. Also required are continuous monitoring of vital signs and oxygen saturation, adequate endoscopy personnel (a nurse to observe the patient, a technician, and individuals trained in the use of pediatric ACLS), adequate equipment (nasogastric suction, pediatric laryngoscopes, and Ambu bags), and an adequate facility where the patient can be observed after completion of the procedure. VOLUME 42, NO. 2, 1995
The use of IV sedation in pediatric UGI endoscopy offers a safe, effective, and less costly alternative to general anesthesia. In this study, successful sedation was achieved in 99% of all elective procedures. Currently, some investigators argue t h a t pediatric endoscopy cannot be performed with IV medication unless deep sedation is achieved. In the above study, in all but five children older t h a n 4 years, a safe EGD was performed under the guidelines of conscious sedation (protection of reflexes and ability to follow commands). In the children aged 4 years or less, a response to voice commands was difficult to interpret, and one could therefore argue t h a t deep sedation may have been used; however, in all cases the gag reflex remained intact and every patient continued to be aroused on insertion of the endoscope. On the other hand, general anesthesia should be used for specific patients. At our institution, we utilize general anesthesia for all patients who are at increased risk for cardiorespiratory complications, who are profoundly mentally retarded, who require therapeutic endoscopy (such as removal of foreign body, balloon dilation, or sclerotherapy), or who are exceedingly anxious or previously failed IV sedation. Although investigators may continue to argue that IV sedation for pediatric endoscopy must utilize deep sedation, this study demonstrates t h a t excellent results can be achieved in a large number of pediatric patients of all ages while adhering to the definition of conscious sedation. It also demonstrates t h a t both meperidine/midazolam and fentanyl/midazolam are safe and effective; however, the results with fentanyl show a significantly shorter recovery time, suggesting that it is associated with fewer side effects when used in combination with midazolam and may be the drug of choice for future endoscopic procedures. REFERENCES
1. AmericanAcademyof Pediatrics Committeeon Drugs: guidelines for monitoring and management of pediatric patients during and after sedationfor diagnosticand therapeuticprocedures. Pediatrics 1992;89:1110-5. 2. BenarochLM, Rudolph CD. Introductionto pediatric esophagogastroduodenoscopyand enteroscopy. Gastrointest Endosc 1994;4:121-42. 3. CookBA, Bass JW, NomizuS, AlexanderME. Sedationofchildren fortechnicalprocedures:current standard ofpractice. Clin Pediatr 1992;31:137-42. 4. Smith C, Rowe RD, Vlad P. Sedation of children for cardiac catheterizationwith ataracticmixture. CanadianAnesthetists SocietyJournal 1985;5:35-43. 5. Waggoner WF. Conscious sedation in predoctoral pediatric dentistry programs. J Dent Educ 1986;50:225-9. 6. Guidelines for the elective use of conscious sedation, deep sedation, and general anesthesia in pediatric patients. Committee on Drugs. Section on anesthesiology.Pediatrics 1985; 76:317-21. 7. ChanLY, Tan CL. Use of intravenous midazolamfor sedation in children undergoingward procedures. Journal of the Singapore Paediatric Society1992;34:30-3. 8. Barr EB, Wynn RL. IV sedation in pediatric dentistry: an GASTROINTESTINAL ENDOSCOPY
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15. Kato S, Nakagawa H, Harada Y, et al. A clinical study &upper gastrointestinal endoscopy in Japanese children. Acta Paediatr Jpn 1991;33:36-42. 16. Andrus CH, Dean PA, Ponsky JL. Evaluation of safe, effective intravenous sedation for utilization in endoscopic procedures. Surg Endosc 1990;4:179-83. 17. Bell GD, Spickett GP, Reeve PA, Mordan A, Logan RF. Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient. Br J Clin Pharmacol 1987;23:241-3. 18. Gilger MA, Jeiven SD, Barrish JO, McCarroll LR. Oxygen desaturation and cardiac arrhythmias in children during esophagogastroduodenoscopyusing conscious sedation. Gastrointest Endosc 1993;39:392-5. 19. Ellett ML. General anesthesia: an alternative to sedation for pediatric endoscopic procedures. Gastroenterology Nursing 1991;13:166-8. 20. Yaster M, Nichols DG, Deshpande JK, Wetzel RC. Midazolamfentanyl intravenous sedation in children: case report of respiratory arrest. Pediatrics 1990;86:463-7.
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