Effects of an Individualized Analgesia Protocol on the Requirements of Medical Interventions After Adenotonsillectomy in Children Based on the Result of a Fentanyl Test: a Randomized Controlled Trial
Phase: NA
Conditions: Analgesia
Sponsor: Children's Hospital of Fudan University

 
 
NCT02990910 
 
 
 
 
 
 
 
The effect of individualized analgesia 
on respiratory adverse events after 
adenotonsillectomy in Children 
—randomized double-blind controlled trial 
 
 
 
 
 
 
                                          2017-2-15 
 
 
 
 

Study protocol 
Study background  
Adenotonsillectomy in children is a common operation in Department of 
ENT, and it is also the main method for treatment of obstructive sleep 
apnea syndrome (OSAS). Clinically, there are a considerable number of 
children with OSAS who underwent adenotonsillectomy, some of which 
are severe OSAS.  
Recurrent nocturnal hypoxemia occurred in children with severe OSAS. 
Their susceptibility to opioids increased and the quantity of opioid 
needed for no pain after operation was less than that of mild children . 
Therefore, the dosage of opioids for postoperative analgesia in children 
with different severity is different. If all children are treated with a small 
dose of opioid analgesics, the analgesic efficacy of mild or non OSAS 
children is not sufficient; if a large dose is used, then severe children are 
prone to respiratory adverse events . Studies have shown that the 
incidence of respiratory adverse events in children with severe OSAS is 
as high as 29.6%, which is about 10 times that of children with mild 
OSAS.Therefore, it is very important to differentiate the patients with 
severe and mild OSAS for targeted individualized use of analgesics in 
children with adenotonsillectomy .  
Since children with severe OSAS have an increased susceptibility to 
opioids, we hypothesized that the sensitivity of children to opioids could 

be judged by the response of respiratory rate to small doses of opioids, 
which can guide the use of long-acting opioids after surgery to reduce 
the incidence of respiratory adverse events. Based on our previous 
studies, we found that the fentanyl test results were correlated with the 
postoperative morphine requirement. Children with positive fentanyl 
test need less morphine requirement (median morphine use was 
30μg/kg), and negative children need less postoperative morphine 
requirement (median morphine use was 50μg/kg) . It shows that the 
conventional analgesic dose (25 μg/kg) is larger for some of the children 
with positive fentanyl, which may increase the incidence of 
postoperative respiratory adverse events . It is small for the children 
with negative fentanyl test, there is a lack of pain relief, which extends 
the duration of pain in children. Fentanyl test cannot identify the 
severity of OSAS, but it can be used to identify children with different 
morphine requirements. Therefore, we hypothesized that individual 
analgesia should be performed according to the results of fentanyl test. 
More amount of morphine in children with positive fentanyl test and 
less amount of morphine in children with negative fentanyl test can 
reduce the incidence of postoperative adverse events in children ,and 
improve the analgesic efficacy of children.  
Objective  
The aim of this study was to verify the hypothesis that individualized 

opioid analgesia regimen according to fentanyl test could decrease the 
incidence of postoperative respiratory adverse events and improve the 
effect of analgesia compared with conventional opioid analgesia 
regimen after adenotonsillectomy in children. 
Materials and Methods 
The study received approval from the Institutional Review Board of the 
Children’s Hospital Fudan university (Human Research Review 
Committee Approval No.2016189) and written parental informed 
consent. In this prospective, double-blind, randomized, controlled 
clinical trial, 280 children scheduled for adenotonsillectomy under 
general anesthesia at the Children’s Hospital from November 2016 
through February 2017 were selected and were randomly divided into 
two groups. One group was conventional opioid analgesia regimen 
group, another was individualized opioid analgesia regimen group. The 
two groups had the same anesthesia regimen. Intubation was performed 
without muscle relaxants after induction with inhaled sevoflurane 
combined with propofol. Anesthesia was maintained with sevoflurane 
and N2O without opioids during the operation. Before extubation, 
spontaneous respiration was recovered, and respiratory rate were 
monitored after administration of 1µg/kg fentanyl intravenously. A 
positive result was defined as a decrease of more than 50% in 
spontaneous respiratory rate. Otherwise it was defined as a negative 

result. Extubation was performed when patients were fully awake, and 
they were transferred to the post-anesthesia care unit (PACU). Pain was 
evaluated based on the Children’s Hospital of Eastern Ontario Pain Score 
(CHEOPS) upon admission into the PACU, and every 10 minutes 
thereafter. Morphine was administered repeatedly every 10 minutes 
until a CHEOPS of 6 was attained. Patients in the individualized group 
with positive results of fentanyl test received morphine 10μg/kg 
intravenously, while patients with negative results received morphine 
50μg/kg intravenously. In the conventional group all patients received 
25μg/kg morphine. The main observation indexes was the incidence of 
respiratory adverse events in PACU, the ratio was the number of 
children who occurred respiratory adverse events to the total number of 
children. Respiratory adverse events were defined as an intervention 
requiring a nurse to maintain the SPO2 ≥95%. Interventions include 
blow-by-oxygen mask, jaw thrust, change the body position, pressure 
ventilation, the need to establish artificial airway (oropharyngeal or 
nasopharyngeal airway, laryngeal mask, the endotracheal tube), drug 
administration 
(succinylcholine 
or 
propofol 
ease 
laryngospasm, 
salbutamol inhalation ease bronchospasm, etc.).Secondary indexes were 
the pain score of children in two groups, and analyzed the persistent 
pain state of children in the two groups by Kaplan-Meier survival 
analysis. 

Statistical Analysis 
the SPSS 23.0（Statistical Package for Social Sciences，IBM）was used to 
analyze the data. The measurement data are tested by normality, and 
the normal distribution is expressed as the mean± standard deviation; 
if the distribution is not normal, it is represented by the median and 
range interquartile. The measurement data with normal distribution and 
homogeneity of variance uses t test, if heterogeneity of variance, use the 
nonparametric test; Chi square test was used to compare the count data. 
Results  
The rate of postoperative respiratory adverse events were the main  
observation indexes, comparative the differences， RR (relative risk) and 
the NNT (number need to treat)。We also compare the median survival 
time of CHEOPS> 6 in the individualized group and conventional group. 
At 20 minutes in the PACU, the proportion of children who reached a 
score of CHEOPS ≤ 6 in the individualized group and conventional 
group . p < 0.05 was considered statistically significant. 
Summary 
There are few studies on how to guide the opioid analgesic dosage in 
children with OSAS according to their sensitivity to opioids. In our study , 
the individualized analgesic regimen guided by fentanyl test may reduce 
the incidence of respiratory adverse events after adenotonsillectomy  
and improve the postoperative safety of children.