Dexmedetomidine Combined With Nalbuphine Advanced Analgesia on the Quality of Recovery After General Anesthesia in Elderly Patients
Phase: PHASE4
Conditions: General Anesthetics，Emergence Agitation
Sponsor: Lili Jia



Dexmedetomidine combined with nalbuphine over-the-top analgesia
on the quality of awakening after general anaesthetic surgery
in elderly patients and perioperative lung protection
20221201
V1.0 , 2022.12.01
Tianjin First Central Hospital
The awakening period of general anaesthesia refers to the
time period between the end of surgery and the patient's
awakening when the infusion of anaesthetic drugs is stopped.
During the initial period of general anaesthesia, the depth of
anaesthesia is reduced, the cerebral cortex is still in a state
of inhibition and the subcortical centres are often
hypersensitive to external stimuli. At this time, factors such
as drug effects, pain, hypoxaemia, unrecognised aspiration,
pneumothorax, urinary retention, tracheal tube irritation and
urinary catheter irritation may induce agitation and cause
dramatic haemodynamic changes. Especially in elderly people
with reduced organ function, this may increase postoperative
complications, prolong the hospital stay and increase hospital
costs. In recent years, several studies have demonstrated that
dexmedetomidine and nalbuphine reduce postoperative agitation
and choking during extubation, respectively, without increasing
the time to extubation. Nalbuphine is a mixed agonist-
antagonist analgesic for opioid receptors, binding to μ, κ
and δ receptors, with a complete agonist effect on κ
receptors and a partial antagonist effect on μ receptors, thus
providing analgesia and sedation. Its analgesic strength is
comparable to that of morphine and can be used to relieve
moderate to severe pain, as well as to reduce visceral pain.
Nalbuphine has few cardiovascular side effects, minimal
respiratory depression and a capping effect. As with other
agonist antagonists, nalbuphine interferes with the adverse

effects associated with pure mu agonists such as nausea,
vomiting and pruritus. Dexmedetomidine is an agonist of the
alpha2 adrenergic receptor, which has analgesic, sedative,
anxiolytic, kinetic stabilizing and stress-reducing effects. It
can activate the α2 receptors in the patient's body, thus
inhibiting the release of norepinephrine in the patient's body,
which in turn has analgesic, sedative and anti-anxiety effects
on the patient. According to relevant reports at home and
abroad, dexmedetomidine can reduce the synthesis and release of
pro-inflammatory factors [such as tumour necrosis factor α and
interleukin 6], inhibit the inflammatory response, improve lung
function and protect the lung. The aim of this study is to
explore whether the combination of the two can provide better
analgesic effect, alleviate patients' discomfort during the
awakening period, and reduce patients' perioperative
inflammation level, improve lung function and protect the lung.
Main research objectives
1. A study to evaluate the combination of dextromethorphan
and nalbuphine on the quality of postoperative awakening in
elderly people undergoing general anaesthesia.
2. A study of the combination of dextromethorphan and
nalbuphine on perioperative levels of inflammation and the
occurrence of pulmonary complications in elderly people
undergoing general anaesthesia.
The occurrence of agitation within 1h after extubation and
the occurrence of pulmonary complications within 7d after
surgery.
Elderly patients aged ≥60 years admitted to the PACU with
a tube after major surgery under general anaesthesia.
For patients aged ≥60 years admitted to the operating room
for general anaesthetic surgery, oxygen was administered by
face mask, intravenous access was opened, blood pressure,
oxygen saturation, ECG and BIS values were monitored; radial

artery puncture was performed under local anaesthesia and
invasive blood pressure was monitored. After triple checking,
general anaesthesia was induced and intravenous
methylprednisolone 40mg, gronobromine 1mg, midazolam 0.05
mg/kg, etomidate 0.3mg/kg, sufentanil 0.5μg/kg, rocuronium
0.6mg/kg was administered. Intraoperative volume control
ventilation was adopted with tidal volume 6-8 mL/kg, frequency
12 times/min and oxygen flow rate 12 times. Intraoperative
ventilation was volume-controlled, with a tidal volume of 6-8
mL/kg, a frequency of 12 breaths/min, an oxygen flow rate of 2
L/min, an inspiratory-to-expiratory ratio of 1:2, and a partial
pressure of carbon dioxide at 30-40 mmHg. Intra-operative
maintenance: use static inhalation compound anaesthesia,
remifentanil 0.05-2.00 μg/(kg-min), propofol 4.0-6.0 mg/(kg-
h), 1%-2% sevoflurane inhalation, intra-operative control of
mean arterial pressure fluctuations not exceeding 20% of the
basal value, BIS maintained between 40-60, 30 min before the
end of the operation, stop sevoflurane, according to the drug
The subjects were divided into group A with continuous
intraoperative pumping of saline and an intravenous push of 5
mL of saline 30 min before the end of surgery; group B with
continuous intravenous pumping of DEX 0.5 μg/kg for 10 min and
an intravenous push of nalbuphine 0.20 mg/kg (5 mL) 30 min
before the end of surgery. At the end of the operation, all
anesthetic drugs were stopped and the patient was transferred
to the PACU with intubation.

The primary outcome of this study was the occurrence of
agitation from the awakening period to 30 min after extubation,
with a Riker sedation-agitation score of 5 to 7 determining the
occurrence of agitation.
Secondary research indicators.
（1）EA occurred 0, 10, 20 and 30 min after PACU extubation.
（2）Chills occurred 0, 10, 20 and 30 min after PACU
tubation.
（3）Postoperative pain was assessed by visual analogue scale
AS) at 0, 10, 20 and 30 min after PACU extubation.
（4）Grading of choking and coughing from awakening to 30 min
ter extubation
(5) Observe the changes in vital signs (heart rate, blood
pressure, oxygen saturation) at 0min, 10min, 20min and 30min
after extubation.
(6) Time of extubation: from discontinuation of anaesthetic
medication to time of extubation.
(7) PACU length of stay: the time from the end of the
procedure to discharge from the PACU.
(8) Oxygenation index: Blood gas analysis was taken from the
radial artery for oxygenation index (PaO2/FiO2) before skin
incision, at the end of surgery and 5 min after extubation.

(1) Age ≥60 years, regardless of gender.
(2) Post-tracheal intubation, ventilator-assisted
ventilation.
(3) Performing general anaesthetic surgery.
(1) Hypersensitivity to the drugs used in this study.
(2) Any sedative, analgesic, antiemetic or antipruritic
medication taken 24 hours prior to surgery.
(3) History of severe bradycardia (heart rate <50
beats/min).
(4) Moderate to severe liver and kidney dysfunction.
(5) Persons with combined neurological disorders.
Termination of the trial is required if the subject meets
one or more of the following criteria.
(1) The emergence of life-threatening complications that
urgently require resuscitation of the patient.
(2) The subject or guardian requests to withdraw from the
trial.
(3) Other circumstances which, in the judgment of the
investigator, warrant withdrawal from the trial.
The primary endpoint of this study was the incidence of
post-operative agitation. The incidence of postoperative
agitation in adults has been reported to be 3.7%-41%. We
based the incidence of postoperative agitation in patients in
the placebo group on a 40% incidence of postoperative
agitation at a design test efficiency (1-β) = 0.8 and a test
level of α = 0.05 (bilateral), which would require 108
patients per group if we expected a 30% reduction in the
incidence of EA with dextromethorphan + nalbuphine
prophylaxis. An estimated 10% of patients dropped out of the
study during the trial; therefore, we planned to recruit 120
patients per group, for a total of 240 patients.
Statistical analysis was performed using SPSS statistical
software. the total incidence of EA was expressed as a
percentage and analysed using the chi-square test. Logistic
regression analysis was used to compare the incidence of EA
in the two groups at different times after extubation, and
the WALD χ2 test was used to estimate the parameters
associated with the two groups at different times after
extubation. flacc scores were expressed as mean ± standard
deviation, and within-group repeated measures ANOVA was
performed. Comparisons between groups at different time
points were made using independent samples t-tests. Where
appropriate, demographic data and anaesthetic characteristics
were analysed using chi-square tests and t-tests. The
incidence of adverse events was expressed as frequencies and
percentages (n, %). The difference was statistically

significant at P<0.05 bilaterally.