Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02715154 |
| Other study ID # |
JSPH-A-1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1
|
| First received |
March 2, 2016 |
| Last updated |
March 24, 2017 |
| Start date |
June 2015 |
| Est. completion date |
November 2015 |
Study information
| Verified date |
March 2017 |
| Source |
The First Affiliated Hospital with Nanjing Medical University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Current cesarean section often chooses spinal anesthesia. And in order to avoid the impact
of drugs on the fetus, before the delivery, anesthesiologist generally don't use sedative or
analgesic drugs. However, the majority of puerperas would appear nervous, anxiety, fear and
other psychological reactions in cesarean section. Although the placental transfer and the
foetal metabolism of dexmedetomidine have been reported and the result show no adverse
effects on neonates, but the placental transfer of dexmedetomidine in intravertebral
anesthesia area was lack of systematical research. This study intends to use of
dexmedetomidine in the cesarean section under epidural anesthesia and investigate its
effects on the parturients' haemodynamics and the neonates' placental transfer and
metabolism.
Description:
Current cesarean section in domestic and overseas often chooses spinal anesthesia. And in
order to avoid the impact of drugs on the fetus, before the delivery, anesthesiologist
generally don't use sedative or analgesic drugs. However, the majority of puerperas would
appear nervous, anxiety, fear and other psychological reactions in cesarean section, and
thus produced a series of stress reactions that not only cause the hemodynamic fluctuating
in anesthesia and operation, but also lead to different degrees of personality and behavior
changed. It causes serious injury to physical and mental health of patients. Dexmedetomidine
is a highly selective α2 receptors agonist (α2-AR) ，it has sedation, analgesia,
antisympathetic pharmacological effects and unique "conscious sedation" without respiratory
depression. At present, dexmedetomidine has been widely used in patients in clinics and
clinical anesthesia, it has been hailed as an"dvocate medicine in modern comfortable
anesthesia."Experiments in animals have shown that dexmedetomidine had no adverse effects on
pregnant rats. In addition, Dexmedetomidine has successful application in preterm infants,
infants and children anesthesia, also has a few for caesarean patients sedation reports.
Although the placental transfer and the foetal metabolism of dexmedetomidine have been
reported and the result show no adverse effects on neonates, but the placental transfer of
dexmedetomidine in intravertebral anesthesia area was lack of systematical research.
The safety of the use of dexmedetomidine on neonatal outcome is a very important issue.
Experimental study on acute exposure of rats to dexmedetomidine at the anticipated delivery
time recorded absence of any adverse effects on perinatal morphology of pups, their birth
weight, crown-rump length, physical growth and postnatal behavioural performances. Others
studied the transfer of clonidine and dexmedetomidine across the isolated perfused human
placenta. Dexmedetomidine disappeared faster than clonidine from the maternal circulation,
while even less dexmedetomidine was transported into the fetal circulation. This was due to
its greater placental tissue retention, the basis for which probably is the higher
lipophilicity of dexmedetomidine.
Umbilical cord blood gas analysis of umbilical vein and umbilical artery in this study was
similar to the results of previous studies . The partial oxygen pressure (PO2) of the
arterial blood gas in the umbilical vein was not significantly affected to the oxygen supply
of the newborn infants. On the other hand, the umbilical arterial blood gas was the most
reliable indicator of the oxygenation index and acid-base status of the fetus. Previous
studies have indicated that the relationship between hydrogen ion concentration(PH), base
excess（BE） and neonatal asphyxia was relatively large, and it was positively related to
growth.
Previous research of in vitro placental perfusion indicated that the transfer rate of
dexmedetomidine through the placenta to foetus was 0.77, and the other study indicated that
the rate of placental transfer of dexmedetomidine in cesarean section operation under
general anesthesia was 0.76. It's indicated that dexmedetomidine can also easily pass
through the placental barrier like other anaesthetic drugs. However, the placental transfer
rate of dexmedetomidine is much lower than that of clonidine(0.85) and that of
remifentanil(0.88), which may be caused by dexmedetomidine being more fat-soluble and easier
to be retained in the placenta.
Recently, there is a published interested case report about the successful use of
dexmedetomidine 1 µg/kg followed with 1 µg/kg/h for 10 minutes before cesarean delivery to
facilitate awake fiberoptic endotracheal intubation patient with spinal muscular atrophy
type III with provided adequate sedation, without respiratory compromise. Although
pharmacokinetic data cannot be determined, this case confirms existing in vitro data that
dexmedetomidine has significant placental transfer. Nevertheless, serious neonatal effects
were not detected. Similarly, others used, i.v. dexmedetomidine successfully as an adjunct
to opioid-based PCA and general anesthesia for the respective provision of labor analgesia
and cesarean delivery anesthesia in a parturient with a tethered spinal cord, with
favourable maternal and neonatal outcome.
Project Objectives:
The investigators hypothesize that application of dexmedetomidine in cesarean section under
epidural anesthesia was conducive to maintaining the stability of hemodynamics of the
patients, reducing patients' anxiety and pain stress during the operations, which also had
no adverse effects on newborns.
The aims of the present study are:
Our research efforts will focus on identifying the effects of 0.5 µg/kg/h dexmedetomidine
for uncomplicated cesarean delivery on the followings.
Hemodynamic [heart rate, systolic and mean blood pressure] changes. The rate of placental
transfer of dexmedetomidine . Apgar score (1 and 5 minute) after delivery. The umbilical
cord venous and arterial blood gases analyses. The sedation of Dexmedetomidine. The
incidence of the major complications (respiratory, cardiovascular events, nausea, vomiting
and other adverse reactions).
Project Design:
Study Design:
The study was approved by the first affiliated hospital ethics committee of Nanjing Medical
University, and the puerperas and their families signed informed consent.
Sampling Site:
I. Patient Selection: patients aged 23-41 years (ASA physical status I-II) scheduled for
elective in about 40 women (American Society of Anesthesiologists [ASA] I and II), with
uncomplicated, singleton pregnancies, who will receive epidural anesthesia. The
investigators will exclude women with a history of cardiac, liver, or kidney diseases;
allergy to amide local anesthetics; epilepsy; those taking cardiovascular medications; and
those with pregnancy-induced hypertension, evidence of intrauterine growth restriction, or
fetal compromise.
II. Anesthesia method
Routine monitoring such as electrocardiogram(ECG), heart rate(HR), saturation of pulse
oxygen(SpO2) were monitored after patient arrived at the operation room. Selected the
forearm vein to open venous access, infused sodium lactate Ringer's solution before
anaesthesia. Then began to epidural anesthesia: The patients were at left side lying
position, the L2,3 gap was chosen for puncture. After determined the success of puncture,
inserted the epidural catheter into the head side, the length of the epidural space is 4cm.
By intraductal injection of 2% lidocaine 3ml, signs of spinal anesthesia were excluded.
Additional 0.75% ropivacaine 10 ~ 20ml was injected to control the level of pain disappear
on thoracic4(T4) or thoracic6(T6) to satisfy the operation needs. After the level of
anesthesia completed, Dex group: dexmedetomidine was continuously infused by 0.5 μg/kg in 10
min, followed with 0.5 μg/kg/hr continuous infusion until the closure of the abdominal.
normal saline(NS)group: Pumped in the same volume of normal saline. In the operation, if the
blood pressure was lower than 70% before anesthesia given ephedrine 10 ~ 15mg, and 0.5mg
atropine was used when the heart rate was lower than 60 beats per minute. All operations
were performed by the same group of maieutologists.
III. The Investigators who will be involved with subsequent postoperative patient assessment
will be blinded of the patient group.
IV. Observational information
Systolic pressure(SBP) and diastolic blood pressure(DBP), heart rate(HR) were recorded at
four time points: before anesthesia(T0), infused 10 min(T1), at the delivery of the
baby(T2), at the end of the operation(T3). Ramsay sedation scales were evaluated at three
time points: before anesthesia (T0), skin incision (T1) and 10min after delivery (T2).
(Ramsay standard for evaluation: 1 point: anxious or restless or both; 2 point: cooperative,
orientated and tranquil; 3 point: responding to commands; 4 point: brisk response to
stimulus; 5 point: sluggish response to stimulus; 6 point: no response to stimulus. The
Apgar scores were evaluated at 1 and 5 minute after the delivery. The urinary volume, the
bleeding volume and the infusion volume during the operation were measured. Adverse effects
such as nausea and vomiting in 24 hour after the operation were recorded. Postoperative
analgesic formula: 12mg butorphanol tartrate, 9mg granisetron hydrochloride, diluted with
normal saline to 100ml. Background dose: 2 milliliter per hour, patient controlled analgesia
(PCA): 0.5 milliliter, locking time:15 minutes.
V. Samples Collection and Analysis For blood gas analysis and the plasma dexmedetomidine
concentrations:
Maternal venous blood samples (MV), umbilical artery(UA) and umbilical vein(UV) will be
collected for blood gas analysis, plasma dexmedetomidine concentrations. concentrations at
points: When the baby was born.
1. Type of samples: centrifuged 3500 revolutions per minute for 5 minutes and separated of
plasma to -20℃ frozen preservation.
2. Laboratory Analysis:
High-performance liquid chromatography-mass spectrometry(HPLC-MS/MS) was then used for
measuring the plasma dexmedetomidine concentrations [concentration of umbilical vein(CUV),
concentration of umbilical artery(CUA) and concentration of maternal vein(CMV)]..
VI. Statistical Analysis: The statistical analysis was performed with SPSS 22.0. The
measurement data are shown as mean ± standard deviation (x±s), the t-test was used for
comparison between the groups, and repeated measures analysis of variance was performed for
comparison within the group; chi-square test was used for comparison of the count data, and
rank-sum test was used for comparison of the level information. p < 0.05 was considered as
statistically significant.
VII. Report Writing: 2 months
