Trial Outcomes & Findings for Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Hyperalgesia Induced by Remifentanil in Patients (NCT NCT02043366)

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

180 participants

Primary outcome timeframe

24 hours after surgery

Results posted on

2016-01-08

Participant Flow

From February 2014 to June 2015, 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, a history of gastrointestinal disease

Participant milestones

Participant milestones
Measure	Normal Saline Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Normal Saline	Flurbiprofen AxetilⅠ Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before anesthesia induction and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Flurbiprofen AxetilⅡ Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before the skin closure and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Butorphanol Butorphanol is intravenously administrated at a dose of 20μg/ kg before anesthesia induction and intraoperative pain management was with remifentanil.	Butorphanol-Flurbiprofen Axetil A dose of 10μg/kg butorphanol and a dose of 0.5mg/kg flurbiprofen axetil are intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil.	Sufentanil Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with sufentanil.
Overall Study STARTED	30	30	30	30	30	30
Overall Study COMPLETED	28	28	28	28	28	28
Overall Study NOT COMPLETED	2	2	2	2	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Normal Saline Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Normal Saline	Flurbiprofen AxetilⅠ Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before anesthesia induction and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Flurbiprofen AxetilⅡ Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before the skin closure and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Butorphanol Butorphanol is intravenously administrated at a dose of 20μg/ kg before anesthesia induction and intraoperative pain management was with remifentanil.	Butorphanol-Flurbiprofen Axetil A dose of 10μg/kg butorphanol and a dose of 0.5mg/kg flurbiprofen axetil are intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil.	Sufentanil Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with sufentanil.
Overall Study Lost to Follow-up	2	2	2	2	2	2

Baseline Characteristics

Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Hyperalgesia Induced by Remifentanil in Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Saline n=28 Participants Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Normal Saline	Flurbiprofen AxetilⅠ n=28 Participants Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before anesthesia induction and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Flurbiprofen AxetilⅡ n=28 Participants Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before the skin closure and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Butorphanol n=28 Participants Butorphanol is intravenously administrated at a dose of 20μg/ kg before anesthesia induction and intraoperative pain management was with remifentanil.	Butorphanol-Flurbiprofen Axetil n=28 Participants A dose of 10μg/ kg butorphanol and a dose of 0.5mg/ kg flurbiprofen axetil are intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil.	Sufentanil n=28 Participants Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with sufentanil.	Total n=168 Participants Total of all reporting groups
Age, Continuous	44.2 years STANDARD_DEVIATION 11.0 • n=39 Participants	45.3 years STANDARD_DEVIATION 9.7 • n=41 Participants	47.9 years STANDARD_DEVIATION 10.0 • n=35 Participants	46.5 years STANDARD_DEVIATION 9.7 • n=31 Participants	45.1 years STANDARD_DEVIATION 7.9 • n=146 Participants	43.5 years STANDARD_DEVIATION 10.8 • n=19 Participants	45.5 years STANDARD_DEVIATION 9.8 • n=147 Participants
Sex: Female, Male Female	28 Participants n=39 Participants	28 Participants n=41 Participants	28 Participants n=35 Participants	28 Participants n=31 Participants	28 Participants n=146 Participants	28 Participants n=19 Participants	168 Participants n=147 Participants
Sex: Female, Male Male	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	0 Participants n=146 Participants	0 Participants n=19 Participants	0 Participants n=147 Participants
Region of Enrollment China	28 participants n=39 Participants	28 participants n=41 Participants	28 participants n=35 Participants	28 participants n=31 Participants	28 participants n=146 Participants	28 participants n=19 Participants	168 participants n=147 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=28 Participants Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil Normal Saline	Flurbiprofen AxetilⅠ n=28 Participants Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before anesthesia induction and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Flurbiprofen AxetilⅡ n=28 Participants Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before the skin closure and intraoperative pain management was with remifentanil Flurbiprofen axetil: Flurbiprofen axetil is intravenously administrated	Butorphanol n=28 Participants Butorphanol is intravenously administrated at a dose of 20μg/ kg before anesthesia induction and intraoperative pain management was with remifentanil.	Butorphanol-Flurbiprofen Axetil n=28 Participants A dose of 10μg/ kg butorphanol and a dose of 0.5mg/ kg flurbiprofen axetil are intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil.	Sufentanil n=28 Participants Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with sufentanil
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm	60.57 g Standard Deviation 22.55	78.29 g Standard Deviation 24.76	68.50 g Standard Deviation 21.98	79.7 g Standard Deviation 20.93	81.64 g Standard Deviation 20.40	89.5 g Standard Deviation 23.4

SECONDARY outcome

Timeframe: 3h, 6h, 12h, and 24h after surgery

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour post surgery

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours

Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 hour after surgery

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours

Each patient was administered analgesics using a PCA pump containing sufentanil (100μg) in normal saline at a total volume of 100 ml after leaving PACU. 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 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.