The Safety、Efficacy and Pharmacokinetics of Dexmedetomidine Administered Through Different Routes in Pediatric
Phase: PHASE4
Conditions: Pediatrics, Dexmedetomidine, Pharmacodynamics, Pharmacokinetics
Sponsor: Chinese Medical Association

                                                      
 
The Safety、Efficacy and Pharmacokinetics of  
Dexmedetomidine Administered Through Different Routes 
 in Pediatric 
 
 
 
October 12,   2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

The safety、efficacy and pharmacokinetics of dexmedetomidine 
administered through different routes in pediatric 
Dexmedetomidine（DEX）is a highly selective α2  adrenoreceptor agonist that 
provides anxiolysis, sedation, and modest analgesia with minimal respiratory 
depression.DEX is approved for use in adults; however, there continues to be no U.S. Food 
and Drug Administration (FDA)-approved label indication for DEX in pediatric patients. 
Nevertheless, DEX has been reportedly used in pediatrics as a premedication,a sedation 
agent for use in the pediatric intensive care unit, an adjunct to inhaled anesthetic agents, 
and a drug for both the prophylaxis and the treatment of emergence agitation (EA) after 
general anesthesia. EA, especially in pediatrics,poses a significant challenge to quality 
patient care. Although 2-, 5-, or 10-minute DEX infusions reduce the incidence of EA in 
children, a rapid bolus injection, if proven to be hemodynamically acceptable, would allow 
a more timely and optimum administration of the drug to both treat and prevent EA. Jooste 
et al had obserbated that rapid IV bolus administration of dexmedetomidine in 12 children 
having undergone heart transplants was clinically well tolerated, although it resulted in a 
transient but significant increase in systemic and pulmonary pressure and a decrease in HR. 
John A et al also reported that rapid IV bolus administration of 0.5µg/kg  DEX in children 
improved their recovery profile by reducing the incidence of EA. Although a statistically 
significant change in hemodynamics was observed, but no patients required any 
intervention for hemodynamic changes.But either a small sample study, or only one dose of 
DEX.Dexmedetomidine is used frequently to prevent and treat postoperative agitation in 
doses of 0.25–1µg/kg ,and it is now common practice in clinical institution to administer 
dexmedetomidine as a rapid (less than 5 seconds) IV bolus.We therefore designed the 
research to study the efficacy 、safety and pharmacokinetics of  different doses of 
dexmedetomidine as a rapid bolus for pediatric patients. 
     On the other hand,our previous study revealed that intranasal dexmedetomidine 
premedication can low the preoperative anxiety and postoperative EA in pediatric.The 
nasal delivery is non-invasive、comfortable and easy to accept by children. So our further 
research is to study the pharmacokinetics after a single dose of dexmedetomidine 
administered as a nasal spray in pediatric. 
1.Acute hemodynamic and respiratory  changes after rapid intravenous 
different doses of dexmedetomidine in Pediatric 
1. 1 Patients’  selection
Inclusion: (1) selective operation of inguinal hernia repair in children; (2) aged 3-9 
years; (3) ASA I - II; (4) enter the operating room by himself without parents; (5) normal 
liver and kidney function; (6) no history of anesthesia medication allergy.  
Exclusion criteria: (1) allergic to dexmedetomidine, similar active ingredients or 
excipients; (2) G-6-PD deficiency; (3) a history of arrhythmia, bronchial and 

cardiovascular diseases, abnormal liver function and so on; (4) a history of use of alpha 2 
receptor agonists or antagonists.  
After obtained informed written consent from all parents, 100 pediatric patients were 
randomly enrolled into five groups: group 1.1: control group; group1.2: 0.25μg/kg 
dexmedetomidine group; group1.3: 0.5μg/kg dexmedetomidine group; group1.4: 0.75μg/kg 
dexmedetomidine group; group1.5:  1μg/kg dexmedetomidine group. 
1.2 Medication 
There was no premedication used. A peripheral venous catheter was placed about 2 h 
before operation on the ward.EMLA_ cream (lidocaine 2.5 % and prilocaine 2.5 %,Astra 
Zeneca Inc., Sweden) was applied to facilitate the venous cannulation. Heart rate, 
noninvasive arterial blood pressure, peripheral arteriolar oxygen saturation, ECG and BIS 
were monitored. After preoxygenation via face mask,anesthesia was induced with propofol 
2–3 mg/kg and inhalation of 6vol％ sevoflurane. After pupil is fixed , put into the LMA 
and do the Ilioinguinal/iliohypogastric nerve block(IINB) to relieve postoperative pain . 
Anesthesia maintained with 2-3vol％ sevoflurane and spontaneous respiration. After the 
vital signs are stable, study groups receive a rapid bolus injection of different dose of DEX 
at a rate of less than 5 seconds, whereas patients in control group received saline in an 
equal volume. 
1.3 Data collection 
HR, SBP,DBP, RR,VT ,Sao2 and BIS will be recorded immediately before the study 
drug injection (baseline) and every minute for 5 minutes thereafter. EA was assessed by the 
study staff upon arrival in the PACU using the Pediatric Anesthesia Emergence 
Delirium(PAED) scale (0–20 scale) and pain score using the mCHOPES scale. The time of 
operation and awakening , and any side-effects such as respiratory/cardiovascular 
depression should be recorded.  
1.4 Technical route 
Different doses of dexmedetomidine as a rapid bolus in pediatric 
0.25µg/kg 
 saline solution 
0.5µg/kg 
0.75µg/kg 
Hemodynamics and respiratory parameters、time of operation and awakening、
scores of PAED and mCHOPES、side-effects 
The safety and efficacy of diffrent doses of dexmedetomidine as a rapid bolus in pediatric 
1µg/kg 

2. Pharmacokinetics after a single rapid intravenous dose of
dexmedetomidine in Pediatric 
2.1 Patients’ selection 
selective operation of orthopedics operation or general surgery operation in children, 
others are the same as 1.1. 48 pediatric patients were randomly enrolled into four groups: 
group2.1: 0.25μg/kg dexmedetomidine group; group2.2: 0.5μg/kg dexmedetomidine group; 
group2.3: 0.75μg/kg dexmedetomidine group; group2.4:  1μg/kg dexmedetomidine group. 
2.2 Medication 
There was no premedication used. A peripheral venous catheter was placed about 2 h 
before operation on the ward.EMLA_ cream (lidocaine 2.5 % and prilocaine 2.5 %,Astra 
Zeneca Inc., Sweden) was applied to facilitate the venous cannulation. Heart rate, 
noninvasive arterial bloodpressure, peripheral arteriolar oxygen saturation, ECG and BIS 
were monitored. After preoxygenation via face mask,anesthesia was induced with propofol 
2–3 mg/kg and inhalation of 6vol％ sevoflurane. After pupil is fixed , put into the LMA 
and different regional nerve block or catheter was carried out to relieve postoperative pain . 
Anesthesia maintained with 2-3vol％ sevoflurane. After the vital signs are stable, study 
groups receive a rapid bolus injection of different dose of DEX at a rate of less than 5 
seconds. 
2.3 Blood sampling 
Venous blood samples of 0.4 ml each were collected at the following times: 1,5, 10, 30, 
60 and 120 min after the end of the infusion of dexmedetomidine. Blood samples were 
drawn into EDTA tubes and stored at 4 ℃. All heparinized blood samples were 
centrifuged within 30 min after collection, and the supernatant plasma was pipetted into 
glass vials and stored at -30℃ immediately after separation. Later on, the samples were 
stored at -80℃ until analysis. Dexmedetomidine plasma concentrations were measured 
with high-performance liquid chromatography and mass spectrometry.  
2.4 Technical route 
Pharmacokinetics after a single rapid Intravenous dose of dexmedetomidine in pediatric 
Collect venous blood samples at 1, 5, 10, 30, 60 and 120 min and measure the 
dexmedetomidine plasma concentrations 
1µg/kg 
0.25µg/kg 
0.5µg/kg 
0.75µg/kg 

3.Pharmacokinetics after a single dose of dexmedetomidine administered 
as a nasal spray in pediatric 
3.1 Patients’ selection 
The same as 2.1,39 pediatric patients were randomly enrolled into three groups: 
group3.1: 1.0 μg/kg dexmedetomidine group; group3.2: 1.5 μg/kg dexmedetomidine group; 
group3.3: 2.0 μg/kg dexmedetomidine group. 
3.2 Medication 
There was no premedication used. A peripheral venous catheter was placed about 2 h 
before operation on the ward.EMLA_ cream (lidocaine 2.5 % and prilocaine 2.5 %,Astra 
Zeneca Inc., Sweden) was applied to facilitate the venous cannulation. Heart rate, 
noninvasive arterial bloodpressure, peripheral arteriolar oxygen saturation, ECG and BIS 
were monitored. After preoxygenation via face mask,anesthesia was induced with propofol 
2–3 mg/kg and inhalation of 6vol％ sevoflurane. After pupil is fixed , put into the LMA 
and different regional nerve block or catheter was carried out to relieve postoperative pain . 
Anesthesia maintained with 2-3vol％ sevoflurane. After the vital signs are stable, study 
groups receive intranasal different dose of DEX .  
3.3 Blood sampling 
Venous blood samples of 0.4 ml each were collected at the following times: 10, 30, 
60,120,180 and 240 min after the end of administration of dexmedetomidine. Blood 
samples were drawn into EDTA tubes and stored at 4 ℃. All heparinized blood samples 
were centrifuged within 30 min after collection, and the supernatant plasma was 
pipetted into glass vials and stored at -30℃ immediately after separation. Later on, the 
samples were stored at -80℃ until analysis. Dexmedetomidine plasma concentrations 
were measured with high-performance liquid chromatography and mass spectrometry. 
3.4 Technical route 
Collect venous blood samples at 10, 30, 60,120,180 and 240 and measure the 
dexmedetomidine plasma concentrations 
1.0µg/kg 
1.5µg/kg 
2.µg/k0g 
Pharmacokinetics of dexmedetomidine as a nasal spray in pediatric