Combination of Nalbuphine and Dexmedetomidine Versus Sufentanil and Dexmedetomidine on Patients

Sponsor

Qianfoshan Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05445024

Collaborator

(none)

300

Enrollment

Location

Arms

Anticipated Duration (Months)

16.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Surgical pain refers to pain that occurs immediately after surgery, including physical pain and visceral pain. Thus, it severely challenges the proper use of analgesics for patients undergoing laparoscope gastrointestinal surgery to clinicians.

Nalbuphine is a mixed agonist-antagonist opioid. The investigators hypothesized that the clinical effect of nalbuphine in combination with dexmedetomidine might be different from that of sufentanil in combination with dexmedetomidine.

So, the investigators performed a nalbuphine and dexmedetomidine dose finding study, for the patient controlled anaesthesia (PCA) after the laparoscopic gastrointestinal surgery, to establish their 95% effective dose (ED95). The investigators then compared the clinical effect and adverse events of the newly established dosing regimen of nalbuphine combined with dexmedetomidine, to the equivalent dosing of sufentanil combined with dexmedetomidine, in the same patient population.

Condition or Disease	Intervention/Treatment	Phase
Laparoscopic Gastrointestinal Surgery	Procedure: nalbuphine group Procedure: sufentanil group	N/A

Detailed Description

Surgical pain refers to pain that occurs immediately after surgery, including physical pain and visceral pain. Appropriate perioperative analgesia is a fundamental component of enhanced recovery after surgery. Especially, 45% of postoperative patients experience inadequate pain after gastrointestinal surgery, and uncontrolled postoperative pain prompts respiratory distress, delays wound healing, and a potentially eventual transition from acute to chronic pain problems. Thus, it severely challenges the proper use of analgesics for patients undergoing laparoscope gastrointestinal surgery to clinicians.

Sufentanil is one of the most common opioid used in patient-controlled analgesia (PCA), it may induce many adverse events including respiratory depression, nausea, vomiting, constipation, urinary retention, pruritus, and drowsiness. Many drugs have been combined with dexmedetomidine in PCA to augment analgesic effect or to reduce the adverse events.

Nalbuphine is a mixed agonist-antagonist opioid. Nalbuphine derives its analgesic and sleep-producing effects through agonism at the kappa-opioid receptor with fewer opioid-induced adverse effects. some articles show that it also has the potential to attenuate the mu-opioid receptor-related adverse events. The investigators hypothesized that the clinical effect of nalbuphine in combination with dexmedetomidine might be different from that of sufentanil in combination with dexmedetomidine. Unfortunately, the optimal dosing of nalbuphine combined with dexmedetomidine for the PCIA after the laparoscopic gastrointestinal surgery, has not been determined.

So, the investigators performed a nalbuphine and dexmedetomidine dose finding study, for the PCIA after the laparoscopic gastrointestinal surgery, to establish their 95% effective dose (ED95). The investigators then compared the clinical effect and adverse events of the newly established dosing regimen of nalbuphine combined with dexmedetomidine, to the equivalent dosing of sufentanil combined with dexmedetomidine, in the same patient population.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Combination of Nalbuphine and Dexmedetomidine Versus Sufentanil and Dexmedetomidine on Patients After Laparoscopic Gastrointestinal Surgery: A Double-blind, Randomized, Controlled Clinical Study

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Aug 30, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: nalbuphine group nalbuphine ED95, dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml	Procedure: nalbuphine group nalbuphine ED95, dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml
Placebo Comparator: sufentanil group sufentanil (1/1000* nalbuphine ED95), dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml	Procedure: sufentanil group sufentanil (1/1000* nalbuphine ED95), dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml

Arm

Intervention/Treatment

Experimental: nalbuphine group

nalbuphine ED95, dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml

Procedure: nalbuphine group

nalbuphine ED95, dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml

Placebo Comparator: sufentanil group

sufentanil (1/1000* nalbuphine ED95), dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml

Procedure: sufentanil group

sufentanil (1/1000* nalbuphine ED95), dexmedetomidine ED95 and ondansetron 16mg were added into normal saline to a total of 100ml

Outcome Measures

Primary Outcome Measures

Visual Analogue Scale (VAS) at rest [At 24 hour after operation]
VAS = a 10 cm VAS for pain (0, no pain; 10, worst imaginable pain)

Secondary Outcome Measures

VAS upon movement [Before leaving post anesthesia care(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
VAS = a 10 cm VAS for pain (0, no pain; 10, worst imaginable pain) upon movement (during coughing or changing body position from supine to lateral on bed)
VAS at rest [At 6 hour(T1), 12 hour(T2), 18 hour(T3) ,48 hour(T5) postoperatively.T1 is defined as 6 hour after surgery.T2 is defined as 12 hour after surgery.T3 is defined as 18 hour after surgery.T5 is defined as 48 hour after surgery.]
VAS = a 10 cm VAS for pain (0, no pain; 10, worst imaginable pain)
VAS at rest [Before leaving post anesthesia care unit (PACU)(T0) .T0 is defined as before the patients leave PACU.]
VAS= a 10 cm VAS for pain (0, no pain; 10, worst imaginable pain) at rest
Brinell comfort score (BCS) [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
the Brinell Comfort Score (BCS) 0. for persistent pain; No pain when quiet, severe pain when deep breathing or coughing; No pain when quiet, mild pain when deep breathing or coughing; No pain when quiet and deep breathing; No pain when coughing.
pressing times of PCIA [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
PCIA(patient controled anesthesia), effective pressing times of PCIA/actual pressing times of PCIA
The number of patients who required remedial analgesic during the first 48h after operation [Within 48hours after surgery]
The number of patients who required remedial analgesic such as opioids(demerol,sufentanil,morphine)or non-steroid anti-inflammatory drugs(acetaminophen,diclofenac).
Frequency of remedial analgesic during the first 48h after operation [Within 48hours after surgery]
Frequency of remedial analgesic during the first 48h after operation
The cumulative remedial analgesic consumption during the first 48h after operation [Within 48hours after surgery]
The cumulative remedial analgesic consumption such as demerol, sufentanil, morphine
PONV [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
PONV (Postoperative nausea and vomiting)=Nausea is defined as subjective,unpleasant sensation associated with awareness of the urge to vomit. Retching is defined as the laboured, spastic, rhythmic contraction of the respiratory muscles without expulsion of the gastric contents.Vomiting is defined as the forceful expulsion of gastric contents from the mouth。0 is no nausea and vomiting; Grade I was nausea without vomiting. Grade Ⅱ was nausea with mild vomiting. Degree III was severe vomiting requiring further treatment. Grade Ⅳ is uncontrollable vomiting. The total number of episodes of vomiting was recorded.
pruritus [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
0, no; 1, mild; 2, moderate; 3, severe.
Frequency of remedial antiemetic during the first 48h after operation [Within 48hours after surgery]
Frequency of remedial antiemetic during the first 48h after operation
The cumulative remedial antiemetic consumption during the first 48h after operation [Within 48hours after surgery]
The cumulative remedial antiemetic consumption during the first 48h after operation
Ramsay sedation score [Before leaving PACU(T0) and at 6hour(T1), 12hour(T2), 18hour(T3), 24hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48h postoperatively, respectively.]
Ramsay sedation score (1, anxious, agitated, or restless; 2, cooperative, oriented, and tranquil; 3, responsive to command; 4, briskly responsive; 5, a sluggish response; 6, no response)
The number of patients who required remedial antiemetic during the first 48h after operation [Within 48hours after surgery]
The number of patients who required remedial antiemetic
hypotension [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
Hypotension was defined as systolic arterial pressure <90 mmHg at any investigated time or mean artetial pressure (MAP) decreased by 30% from baseline..
respiratory depression [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
Respiratory depression was defined as ventilatory frequency,8 min-1 or hypoxaemia (SpO2<90%).
dizziness [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
0, no; 1, mild; 2, moderate; 3, severe.
sufentanil [Before leaving PACU(T0). T0 is defined as before the patients leave PACU.]
Sufentanil amount in intraoperative and PACU
Satisfaction rating [T5 is defined as 48 hour after surgery.]
Patients and clinicians were evaluated from three aspects: analgesia effect, sedation and overall evaluation.(0, very dissatisfied;100 points, very satisfied.Score according to actual situation)
HR [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) ad 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48hour postoperatively, respectively.]
heart rate
NBP [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
noninvasive arterial pressure,
SpO2 [Before leaving PACU(T0) and at 6 hour(T1), 12 hour(T2), 18 hour(T3), 24 hour(T4) and 48 hour (T5)postoperatively.T0 is defined as before the patients leave PACU.T1-T5 were defined as 6,12,18,24 and 48 hour postoperatively, respectively.]
oxygen saturation
Time for leaving the bed [at discharge (assessed up to day 7)]
Time for patients to leave the bed and walk
Time for intestinal movement [at discharge (assessed up to day 7)]
Intestinal movement=The patient passed gas for the first time
Time for drinking [at discharge (assessed up to day 7)]
Time for drinking= The patient drink water for the first time
Time for eating [at discharge (assessed up to day 7)]
Time for eating= The patient eat food for the first time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

age ≥18 years and ≤75 years;
scheduled to undergo laparoscopic gastrointestinal surgery, under general anaesthesia;
18.5 kg/m2≤BMI≤27.9kg /m2;
American Society of Anesthesiology (ASA) I-III;
agree to participate, and give signed written informed consents;
Verbal or reading ability, able to understand and complete the questionnaire independently or with the help of doctors.

Exclusion Criteria:

patients who were allergic to the drugs in this study, who refused to use analgesic devices and analgesic drugs after operation, or who refused to sign the consent forms were not included;
severe hypertension, severe psychiatric disease and mental system diseases, severe respiratory diseases, hyperthyroidism, severe liver and kidney dysfunction, alcohol or drug abuse, Severe heart dysfunction or pulmonary insufficiency,Previous history of schizophrenia, epilepsy, myasthenia gravis or delirium;
Patients who had a history of drug abuse, patients undergoing chemotherapy and radiotherapy one month before operation, patients unwilling to cooperate with the treatment or with disabilities, were excluded from the study;
Patients with a definite diagnosis of chronic pain syndrome, or substance use disorder, patients who used sedatives, antiemetics, or anti-pruritic agents within 24 h before operation;
participating in other clinical studies in recent 3 months.