What Is Known/What Is New
What Is Known
- Pediatric upper gastrointestinal endoscopy is performed more effectively on deeply sedated patients.
- Use of inhaled anesthetics in children, while feasible, causes several postoperative complications; mainly nausea and vomiting and emergence delirium.
What Is New
- With a rich history as an antiemetic, more recently, preoperative dexamethasone has been used effectively to improve recovery after some pediatric operations.
- A single preoperative dose of dexamethasone for children under deep sedation with inhaled anesthetics can reduce postoperative nausea and vomiting after pediatric endoscopy with no further complications.
See “The Deep Sedation Conundrum and Paediatric Endoscopy” by Turnbull and Thomson on page 271.
Upper gastrointestinal endoscopy (UGIE) in pediatric patient population has been performed with increasing diagnostic and therapeutic applications (1). Although it can be completed with no or mild sedation (2), sufficient sedation and procedural anesthesia for children, provides patient comfort and cooperation and enhances the feasibility and effectiveness of the ongoing procedure (3,4). No specific sedation form has been proposed for all patients (4,5). Although preferences vary, the profile of potential side effects remains an important factor in choosing the appropriate anesthetic regimen for younger patient populations (6,7).
Postoperative nausea and vomiting (PONV) is a frequent complication in pediatric anesthesia, with rates of incidence twice as high compared with adult patients (8,9). It can in turn slow patient recovery, delay discharge, and therefore increase medical costs (10). Bronchospasm or laryngospasm and postanesthesia emergence delirium are other UGIE complications that have higher frequencies in children recovering from deep sedation (11,12).
Sevoflurane is a proper inhalational anesthetic for elective UGIE in children (13). It is relatively safe, inexpensive, and has comparable recovery periods to the intravenous agents (14); but it can increase the rates of PONV (15,16) and emergence delirium (17). To address the issue, several works have studied using different regimens, to reduce the incidence of PONV (18,19) and emergence delirium (20) after moderate to deep sedation or general anesthesia.
Dexamethasone was first reported as an antiemetic drug in patients undergoing chemotherapy (21,22), and more recently its effectiveness in reducing PONV has been shown in several adult and pediatric procedures (10,23). Although prophylactic dexamethasone can also reduce other postoperative complications including pain (24) and emergence delirium (25), medical literature lacks sufficient evidence on its potential efficacy in reducing PONV and recovery time after UGIE.
This work aims to test this hypothesis and study the effect of a single dose of preoperative intravenous (i.v.) dexamethasone, primarily in reducing PONV, and secondarily on the incidence of bronchospasm or laryngospasm, emergence delirium, and reduction of patient recovery time after elective UGIE procedures, performed on deeply sedated children.
Design and Oversight
The following study was designed as a prospective single-center, 2-arm parallel group, double-blind randomized controlled trial. Research protocol was approved by the Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran, on October 17, 2018 and registered at the Iranian Registry of Clinical Trials on October 26, 2018 (Number IRCT20180929041173N1 at irct.ir). This research was conducted on children referred to the Endoscopy ward of Children's Medical Center hospital (Tehran, Iran) during November 2018, after obtaining a written informed consent from their parents or legal guardians.
Children aged 2 to 14, with ASA physical status I-II (ie, healthy or with a mild systemic disease) (26) who were a candidate for elective UGIE with deep sedation (based on the diagnosis by a pediatric gastroenterologist), were considered eligible for inclusion. The following were excluded from this study: children with a history of hypersensitivity to the drugs studied; a history of previous chemotherapy treatment, malignancy, metabolic disease, or diabetes; patients suffering from anatomical upper airway disorders; diagnosed with behavioral disorders or currently taking psychiatric medication; children who had taken a sedative/hypnotic drug before the operation; patients who were a candidate for endoscopic retrograde cholangiopancreatography or an emergency endoscopic procedure; and patients whose operation was complicated and took too long to be completed and therefore could have potentially received more quantities of anesthetics (In retrospect, no patient had to be subjected to the final exclusion criteria).
Based on data presented in previous works (15,21), frequency of the main outcome (PONV incidence) was assumed to be 5% and 25% in the intervention groups. To have a power of 80% to detect this potential difference in the PONV incidence with type I error of 5%, a sample size of 47 for each group was calculated. To compensate for the possible loss of information, we estimated it was necessary to enroll 49 subjects in each study group.
Patient Enrollment and Allocation
As shown in Supplemental Figure 1 (Patient Flow Diagram, from CONSORT 2010 statement, http://links.lww.com/MPG/B657), in a period of 18 days, from the total of 134 patients observed, 98 patients were enrolled; 34 patients did not match the defined criteria; and 2 patients’ guardians declined to participate and therefore were excluded from the trial. After written informed consent was obtained from parents or legal guardians, the enrolled children were randomly assigned to dexamethasone groups (DEX groups) and control groups in 1:1 allocation ratio. A computer software tool was used to generate the random sequence for permuted block randomization with random block sizes of 2, 4, and 6. Based on the random sequence, intervention allocation was carried out using sequential sealed opaque envelopes prepared by an external assistant not involved in the trial process. Therefore the treatment allocation was properly concealed from all investigators and care givers.
All the UGIE procedures were performed by 4 board-certified pediatric gastroenterologists and 2 registered endoscopy assistants, under supervision of a senior anesthesiology resident. Procedural methods were decided beforehand and all patients underwent the same procedural techniques. Patients were not allowed solid food intake from the night before, but clear liquids were permitted until 4 hours to the operation. For all patients i.v. cannula was inserted, standard patient monitoring was established and vital signs were recorded. During operation patients were monitored continuously for heart rate, blood pressure, respiratory rate, and O2 saturation. Anesthesia was induced with 2.5 mg/kg i.v. sodium thiopental and was maintained with 2% to 2.5% sevoflurane in oxygen while breathing spontaneously. A procedural (endoscopy) mask with a dedicated endoscope opening was used, which allowed for continuous anesthetic/oxygen delivery throughout the procedure with no interruption or leaking. Children were deeply sedated for the procedure, that is, they were not easily arousable, but could respond following repeated or painful stimulation. Before the commencement of UGIE, when the adequate sedation was reached, patients in dexamethasone group received 0.1 mg/kg i.v. dexamethasone, and patients in the control group received 2 cm3 i.v. 0.9% saline. Nurses not involved in the study design, prepared dexamethasone or 0.9% saline in similar looking containers according to the random sequence of group assignments, and an investigator blind to the allocated drugs performed the drug administration. At the end of the procedure patients were first transferred to postanesthesia care unit (PACU) then, when eligible (explained later), to the secondary recovery facilities of the endoscopy ward.
Baseline characteristics including sex, age, and weight of all the children were recorded preoperatively.
An investigator (a medical doctor) blinded to the patient drug assignments examined and recorded the incidence of PONV as the primary outcome of this study. Because using subjective measures in younger patients could lead to unreliable results, presence of either subjective feeling of nausea (as expressed by the patients) or objective vomiting or retching in postoperative patients were considered as a positive PONV outcome. Among patients with positive PONV, rescue therapy with i.v. ondansetron was saved for patients with more than 1 episode of vomiting, patients with nausea after a single episode of vomiting and patients who were otherwise eligible for discharge but had persistent nausea.
Data were also collected on the following secondary outcomes: The incidence of bronchospasm or laryngospasm was examined and recorded. Postanesthesia emergence delirium was assessed using the Pediatric Anesthesia Emergence Delirium Scale (Table 1). Patient recovery from anesthesia was assessed using Modified Aldrete (MA) score for postanesthetic recovery (Table 2) (27) at the time of entry to PACU (0 minutes) and at 5 minutes after endoscopy. Patients were eligible for transfer from PACU to the secondary recovery facilities when they scored 9 or 10 on MA. After the operation for each child patient recovery time, defined as the total time period of their stay in PACU (and not the secondary facilities), was recorded. Children were discharged from secondary recovery facilities in presence of a responsible adult; when they were fully conscious, oriented, and responding (with regard to their age); scored at least 9 on MA; had stable cardiovascular function and airway patency; had recovered from ED or any other complications (if positive); and could drink clear liquids without nausea/vomiting.
Data collection and patient enrollment were terminated when complete data on all variables were collected for the required sample size. Throughout the trial blinding on patient drug assignments was carried out for all participants, data collectors, and care givers. There were no changes to any part of the study methods after trial commencement and all the subjects completed the course of this study in their randomly allocated intervention groups without protocol deviation (Supplemental Figure 1, http://links.lww.com/MPG/B657). There was no loss to follow-up and no patient data were missed. No outliers were recorded regarding the patient population, procedure duration, quantity of anesthetic used, or measures of any of the primary or secondary outcomes.
Statistical analysis was performed to compare data on baseline and outcome variables between dexamethasone group and the control group. Continuous normal variables were compared with the Student t test, categorical variables using Chi-square and Fisher's exact test and ordinal variables using nonparametric Mann-Whitney test. P value <0.05 was regarded as statistically significant. The statistical computer package IBM SPSS Statistics version 25 (IBM CO, Armonk, NY) was used for data analysis.
Overall, 98 patients were studied. Randomly, 49 patients (27 girls , 22 boys, mean age 7.8 years, mean weight 25 kg) received dexamethasone (DEX group), and 49 patients (20 girls, 29 boys, mean age 7.2 years, mean weight 23 kg) received 0.9% saline (control group). As presented in Table 3, none of the baseline characteristics were significantly different between the 2 groups and they were demographically comparable.
As shown in Table 4, a total of 17 (17.3%) patients experienced PONV. The incidence of nausea and vomiting was less in dexamethasone group (8.2%) compared with the control group (26.5%) (Supplemental Figure 2, http://links.lww.com/MPG/B657). This difference was statistically significant (P = 0.016) as shown in absolute (risk difference: 18.3%; 95% confidence interval [CI]: 3.4%–33%) and relative terms (relative risk: 0.31; 95% CI: 0.11–0.88). It can be estimated for prophylactic administration of dexamethasone to prevent 1 incident of PONV, about 6 patients need to be treated.
The incidence of bronchospasm or laryngospasm between dexamethasone group (4.1%) and control group (4.1%) showed no difference (0, P = 1).
For emergence delirium scores calculated with Pediatric Anesthesia Emergence Delirium scale, the mean ± SD equaled 5.9 ± 3.4 in dexamethasone group and 5.7 ± 3.2 in control group. This difference was not statistically significant (0.2, 95% CI: −1.13–1.54, P = 0.751).
Patient recovery from anesthesia was examined by MA score at 2 different occasions. At the time of patient entry to PACU (0 minutes) and 5 minutes later. Respectively, the median (range) score was 10 (7–10) and 10 (7–10) for dexamethasone group and 10 (7–10) and 10 (6–10) for control group. The difference was not significant at any of the occasions (P = 0.909 and P = 0.527, respectively).
Mean ± SD for patient recovery time (total time period of stay in PACU) was 21.1 ± 6.6 minutes in dexamethasone group and 23.4 ± 8.6 minutes in the control group but this difference was not statistically significant (difference = 2.35 minutes, 95% CI: −0.70–5.40, P = 0.130).
Especially in the pediatric patient population, PONV is a common complication of UGIE (10,11). In children, performing UGIE under deep sedation with agents like sevoflurane offers several advantages (13) but can increase PONV incidence (15,16). Reducing PONV can help decrease patient morbidity and costs (18).
Dexamethasone is a glucocorticoid that can exert antiemetic properties through different pharmacological mechanisms (28). Several studies have shown its effects in reducing PONV in children after different procedures such as adenotonsillectomy (21), laparoscopic, and strabismus surgeries (29), but evidence of its effectiveness in reducing PONV in gastrointestinal endoscopic procedures has been insufficient.
This randomized, placebo-controlled trial showed a single dose of 0.1 mg/kg preoperative dexamethasone, reduces PONV in pediatric UGIE with deep sedation. Results of this study show the size and direction of dexamethasone effect in reducing PONV incidence is consistent with existing research of its effectiveness in other surgeries, as previously shown in several works including important RCTs (23,30), reviews, and meta-analyses (9,18,29). Exploring this antiemetic effect further with future trials can help dexamethasone have a more established role in pragmatic guidelines on pediatric procedural sedation.
It was hypothesized that reducing PONV may shorten patient recovery time and facilitate patient discharge. In this study, patient postanesthesia recovery state assessed with MA scores on 2 time points (0 and 5 minutes) were not improved by dexamethasone and the recovery time of patients in the 2 intervention groups were not significantly different. These results could be explained by the similar incidence of complications other than PONV such as emergence delirium. Emergence delirium is a common postoperative complication in pediatric procedures and a known factor for delaying patient discharge (17,31). Although some studies had shown a positive dexamethasone effect in reducing emergence delirium (25,32), this study was inconsistent and failed to show a significant difference (based on PAED scores) between the 2 groups. Excluding children with behavioral and severe systemic disorders (who are more susceptible to this complication) (17) may have played a role in this matter. To clarify inconsistencies, more studies with appropriate sample sizes are recommended to investigate the effect of dexamethasone on recovery time and emergence delirium as primary outcomes in other patient populations. Use of dexamethasone combined with other pharmacologic or nonpharmacologic interventions (33) to reduce emergence delirium in UGIE with sevoflurane anesthesia can be another promising research subject.
Incidence of bronchospasm or laryngospasm was rather low in both groups and receiving dexamethasone did not show an effect. As subjects of this study in both groups had overall low risk of this complication, research conducted in patients with higher risk of postanesthesia respiratory complications can investigate this effect further.
This study gains its strength from the randomized controlled design, proper allocation concealment and blinding, clearly defined endpoint, inclusion and exclusion criteria, and meticulous adherence to its protocol. This work bears some limitations. Subjects of this research had ASA status of I-II, and patients with metabolic and severe systemic diseases were excluded. Therefore further research is required to evaluate the effect of dexamethasone on PONV and other UGIE complications including pain (34) and its potential side effects in the mentioned patient populations. In addition, these results may not be generalizable to emergency UGIE procedures. Furthermore, the antiemetic effect of dexamethasone combined with other sedation regimens which are in common use for UGIE (2–4), was not explored in this work and can be a subject for future investigations.
In conclusion this study showed a single preoperative dose of i.v. dexamethasone reduces PONV in children following elective UGIE with deep sedation, but has no significant effect on the postoperative patient recovery time, postanesthesia emergence delirium, and the incidence of bronchospasm or laryngospasm.
The authors would like to thank Dr H. Alimadadi, Dr F. Farahmand, Dr F. Motamed, and Dr M. Najafi, members of Department of Pediatrics at Tehran University of Medical Sciences, who acted as scientific advisors and supported this study.
1. Tringali A, Thomson M, Dumonceau JM, et al. Pediatric gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guideline executive summary. Endoscopy
2. Early DS, Lightdale JR, Vargo JJ 2nd, et al. ASGE Standards of Practice Committee. Guidelines for sedation and anesthesia in GI endoscopy. Gastrointest Endosc
3. Van Beek E, Leroy P. Safe and effective procedural sedation for gastrointestinal endoscopy in children. J Pediatr Gastroenterol Nutr
4. Oh SH. Sedation in pediatric esophagogastroduodenoscopy. Clin Endosc
5. Gilger MA. Sedation for pediatric GI endoscopy. Gastrointest Endosc
6. Lightdale JR, Mahoney LB, Schwarz SM, et al. Methods of sedation in pediatric endoscopy: a survey of NASPGHAN members. J Pediatr Gastroenterol Nutr
7. Motamed F, Aminpour Y, Hashemian H, et al. Midazolam-ketamine combination for moderate sedation in upper GI endoscopy. J Pediatr Gastroenterol Nutr
8. Amornyotin S. Sedation-related complications in gastrointestinal endoscopy. World J Gastrointest Endosc
9. Höhne C. Postoperative nausea and vomiting
in pediatric anesthesia. Curr Opin Anaesthesiol
10. Cao X, White PF, Ma H. An update on the management of postoperative nausea and vomiting
. J Anesth
11. Friedt M, Welsch S. An update on pediatric endoscopy. Eur J Med Res
12. Kim YJ. General considerations and updates in pediatric gastrointestinal diagnostic endoscopy. Korean J Pediatr
13. Montes RG, Bohn RA. Deep sedation with inhaled sevoflurane for pediatric outpatient gastrointestinal endoscopy. J Pediatr Gastroenterol Nutr
14. Ebert TJ, Robinson BJ, Uhrich TD, et al. Recovery from sevoflurane anesthesia: a comparison to isoflurane and propofol anesthesia. Anesthesiology
15. Bedi A, Gallagher A, Fee JP, et al. Postoperative nausea and vomiting
following 8% sevoflurane anaesthesia. Anaesthesia
16. Matsuura H, Inoue S, Kawaguchi M. The risk of postoperative nausea and vomiting
between surgical patients received propofol and sevoflurane anesthesia: a matched study. Acta Anaesthesiol Taiwan
17. Sikich N, Lerman J. Development and psychometric evaluation of the Pediatric Anesthesia Emergence Delirium scale. Anesthesiology
18. Kovac AL. Management of postoperative nausea and vomiting
in children. Paediatr Drugs
19. Gan TJ, Diemunsch P, Habib AS, et al. Society for Ambulatory Anesthesia. Consensus guidelines for the management of postoperative nausea and vomiting
. Anesth Analg
20. Jung HJ, Kim JB, Im KS, et al. Effect of ketamine versus thiopental sodium anesthetic induction and a small dose of fentanyl on emergence agitation after sevoflurane anesthesia in children undergoing brief ophthalmic surgery. Korean J Anesthesiol
21. Fazel MR, Yegane-Moghaddam A, Forghani Z, et al. The effect of dexamethasone on postoperative vomiting
and oral intake after adenotonsillectomy. Int J Pediatr Otorhinolaryngol
22. Herrstedt J, Roila F, Warr D, et al. 2016 Updated MASCC/ESMO Consensus Recommendations: prevention of nausea and vomiting
following high emetic risk chemotherapy. Support Care Cancer
23. Apfel CC, Bacher A, Biedler A, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting
24. Vlok R, Melhuish TM, Chong C, et al. Adjuncts to local anaesthetics in tonsillectomy: a systematic review and meta-analysis. J Anesth
25. Dahmani S, Delivet H, Hilly J. Emergence delirium in children: an update. Curr Opin Anaesthesiol
26. Aplin S, Baines D, DE Lima J. Use of the ASA physical status grading system in pediatric practice. Paediatr Anaesth
27. Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth
28. Pappas AL, Sukhani R, Hotaling AJ, et al. The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy. Anesth Analg
29. Maitra S, Som A, Baidya DK, et al. Comparison of ondansetron and dexamethasone for prophylaxis of postoperative nausea and vomiting
in patients undergoing laparoscopic surgeries: a meta-analysis of randomized controlled trials. Anesthesiol Res Pract
30. Hermans V, De Pooter F, De Groote F, et al. Effect of dexamethasone on nausea, vomiting
, and pain in paediatric tonsillectomy. Br J Anaesth
31. Moore AD, Anghelescu DL. Emergence delirium in pediatric anesthesia. Paediatr Drugs
32. Khalili G, Sajedi P, Shafa A, et al. A randomized evaluation of intravenous dexamethasone versus oral acetaminophen codeine in pediatric adenotonsillectomy: emergence agitation and analgesia. Middle East J Anaesthesiol
33. Kain ZN, Mayes LC, Wang SM, et al. Parental presence and a sedative premedicant for children undergoing surgery: a hierarchical study. Anesthesiology
34. Waldron NH, Jones CA, Gan TJ, et al. Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis. Br J Anaesth