Trial Outcomes & Findings for Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia (NCT NCT03096730)

Results Overview

The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament at 24 hours postoperatively

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

150 participants

Primary outcome timeframe

24 hours after surgery

Results posted on

2021-08-03

Participant Flow

From February 2017 to September 2017, patients were recruited and estimated for eligibility

Exclusion criteria: coronary heart disease, bronchial asthma, cardiac, lung, hepatic and renal insufficiency, severe hypertension, diabetes mellitus, psychiatric disease, obesity, a history of chronic pain, a history of alcohol or opioid abuse, pregnancy, allergy and contraindication to study drugs.

Participant milestones

Participant milestones
Measure	Normal Saline Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Normal saline: Normal saline is intravenously administrated before anesthesia induction Remifentanil: Remifentanil is intravenously administrated	Sufentanil Normal saline is intravenously admistrated before anesthesia induction and intraoperative pain management was with sufentanil Normal saline: Normal saline is intravenously administrated before anesthesia induction Sufentanil: Sufentanil is intravenously administrated	Dexmedetomidine Dexmedetomidine is intravenously administrated at a dose of 0.4ug/kg 10min before anesthesia induction until 30min prior to the end of surgery and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Dexmedetomidine: Dexmedetomidine is intravenously administrated before anesthesia induction	Nalmefene Nalmefene is intravenously administrated at a dose of 0.3ug/kg before anesthesia induction and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Nalmefene: Nalmefene is intravenously administrated before anesthesia induction	Dexmedetomidine-Nalmefene A dose of 0.3ug/kg nalmefene and a dose of 0.4ug/kg dexmedetomidine for 10 minutes before anesthesia induction until 30min prior to the end of surgery and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Dexmedetomidine: Dexmedetomidine is intravenously administrated before anesthesia induction Nalmefene: Nalmefene is intravenously administrated before anesthesia induction
Overall Study STARTED	30	30	30	30	30
Overall Study COMPLETED	27	27	27	27	27
Overall Study NOT COMPLETED	3	3	3	3	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Saline n=27 Participants Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Normal saline: Normal saline is intravenously administrated before anesthesia induction Remifentanil: Remifentanil is intravenously administrated	Sufentanil n=27 Participants Normal saline is intravenously admistrated before anesthesia induction and intraoperative pain management was with sufentanil Normal saline: Normal saline is intravenously administrated before anesthesia induction Sufentanil: Sufentanil is intravenously administrated	Dexmedetomidine n=27 Participants Dexmedetomidine is intravenously administrated at a dose of 0.5ug/kg 10min before anesthesia induction and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Dexmedetomidine: Dexmedetomidine is intravenously administrated before anesthesia induction	Nalmefene n=27 Participants Nalmefene is intravenously administrated at a dose of 0.2ug/kg before anesthesia induction and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Nalmefene: Nalmefene is intravenously administrated before anesthesia induction	Dexmedetomidine-Nalmefene n=27 Participants A dose of 0.2ug/kg nalmefene and a dose of 0.5ug/kg dexmedetomidine for 10 minutes before anesthesia induction and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Dexmedetomidine: Dexmedetomidine is intravenously administrated before anesthesia induction Nalmefene: Nalmefene is intravenously administrated before anesthesia induction	Total n=135 Participants Total of all reporting groups
Age, Continuous	47.0 years STANDARD_DEVIATION 5.0 • n=27 Participants	46.0 years STANDARD_DEVIATION 8.0 • n=27 Participants	45.0 years STANDARD_DEVIATION 12 • n=27 Participants	47.0 years STANDARD_DEVIATION 10 • n=27 Participants	46.0 years STANDARD_DEVIATION 9 • n=27 Participants	46.2 years STANDARD_DEVIATION 8.8 • n=135 Participants
Sex: Female, Male Female	27 Participants n=27 Participants	27 Participants n=27 Participants	27 Participants n=27 Participants	27 Participants n=27 Participants	27 Participants n=27 Participants	135 Participants n=135 Participants
Sex: Female, Male Male	0 Participants n=27 Participants	0 Participants n=27 Participants	0 Participants n=27 Participants	0 Participants n=27 Participants	0 Participants n=27 Participants	0 Participants n=135 Participants
Race and Ethnicity Not Collected	—	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment China	27 participants n=27 Participants	27 participants n=27 Participants	27 participants n=27 Participants	27 participants n=27 Participants	27 participants n=27 Participants	135 participants n=135 Participants
Weight	60 Kg STANDARD_DEVIATION 7 • n=27 Participants	57 Kg STANDARD_DEVIATION 8 • n=27 Participants	59 Kg STANDARD_DEVIATION 7 • n=27 Participants	58 Kg STANDARD_DEVIATION 5 • n=27 Participants	60 Kg STANDARD_DEVIATION 8 • n=27 Participants	59 Kg STANDARD_DEVIATION 7 • n=135 Participants

PRIMARY outcome

Timeframe: 24 hours after surgery

The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament at 24 hours postoperatively

Outcome measures

Outcome measures
Measure	Normal Saline n=27 Participants Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Normal saline: Normal saline is intravenously administrated before anesthesia induction Remifentanil: Remifentanil is intravenously administrated	Sufentanil n=27 Participants Normal saline is intravenously admistrated before anesthesia induction and intraoperative pain management was with sufentanil Normal saline: Normal saline is intravenously administrated before anesthesia induction Sufentanil: Sufentanil is intravenously administrated	Dexmedetomidine n=27 Participants Dexmedetomidine is intravenously administrated at a dose of 0.4ug/kg 10min before anesthesia induction until 30min prior to the end of surgery and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Dexmedetomidine: Dexmedetomidine is intravenously administrated before anesthesia induction	Nalmefene n=27 Participants Nalmefene is intravenously administrated at a dose of 0.3ug/kg before anesthesia induction and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Nalmefene: Nalmefene is intravenously administrated before anesthesia induction	Dexmedetomidine-Nalmefene n=27 Participants A dose of 0.3ug/kg nalmefene and a dose of 0.4ug/kg dexmedetomidine for 10 minutes before anesthesia induction until 30min prior to the end of surgery and intraoperative pain management was with remifentanil Remifentanil: Remifentanil is intravenously administrated Dexmedetomidine: Dexmedetomidine is intravenously administrated before anesthesia induction Nalmefene: Nalmefene is intravenously administrated before anesthesia induction
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm	61.5 g Standard Deviation 6.0	88.2 g Standard Deviation 23.40	73.0 g Standard Deviation 3.2	67.2 g Standard Deviation 3.3	74.0 g Standard Deviation 9.3

SECONDARY outcome

Timeframe: 1hours,3hours，6hours，12hours，24hours after surgery

The skin around the incision is stimulated in steps of 5 mm at intervals of 1 s starting outside of the hyperalgesic area in the direction of the incision. The distance from the incision to the first point where a 'painful', 'sore' or 'sharper' feeling occurred is measured and noted. This measurement is repeated at predefined radial lines around the incision. To eliminate the variable length of incision, this length is subtracted from the longer diameter leaving four radial distances from the end and from the middle of the incision. The normalized area of hyperalgesia is calculated by summing up the areas of the remaining four triangles measured by and Von Frey filament.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1hours,3hours，6hours，12hours，24hours after surgery

The pain score at rest was evaluated by pain 11-point numerical rating scale : 0 = no pain, 10 = greatest imaginable pain.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: postoperative 1 hours

First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1hours,3hours，6hours，12hours，24hours after surgery

Each patient was administered analgesics using a PCA pump containing sufentanil (100μg) in normal saline at a total volume of 100 ml after leaving post-anaesthesia care unit . This device was set to deliver a basal infusion of 2 ml/h and bolus doses of 0.5 ml with a 15-min lockout period. Sufentanyl cumulative consumption is recorded 24 hours postoperatively

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours

Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus，hypotention/hypertention，bradycardia/tachycardia