Clinical trial NCT05445024: Combination of Nalbuphine and Dexmedetomidine Versus Sufentanil and Dexmedetomidine on Patients
Official title: Combination of Nalbuphine and Dexmedetomidine Versus Sufentanil and Dexmedetomidine on Patients After Laparoscopic Gastrointestinal Surgery: A Double-blind, Randomized, Controlled Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Laparoscopic
Gastrointestinal Surgery
Keywords: laparoscopic
gastrointestinal surgery
nalbuphine
sufentanil
patient-controlled intravenous analgesia
dexmedetomidine
Lead sponsor: Qianfoshan Hospital
Sponsor class: OTHER
First posted: 2022-07-06
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: Inclusion Criteria:

1. age ≥18 years and ≤75 years;
2. scheduled to undergo laparoscopic gastrointestinal surgery, under general anaesthesia;
3. 18.5 kg/m2≤BMI≤27.9kg /m2;
4. American Society of Anesthesiology (ASA) I-III;
5. agree to participate, and give signed written informed consents;
6. Verbal or reading ability, able to understand and complete the questionnaire independently or with the help of doctors.

Exclusion Criteria:

1. 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;
2. 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;
3. 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;
4. 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;
5. participating in other clinical studies in recent 3 months.

Primary outcomes:
measure: Visual Analogue Scale (VAS) at rest
timeFrame: At 24 hour after operation
Secondary outcomes:
measure: VAS upon movement
timeFrame: 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.
measure: VAS at rest
timeFrame: 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.
measure: VAS at rest
timeFrame: Before leaving post anesthesia care unit (PACU)(T0) .T0 is defined as before the patients leave PACU.
measure: Brinell comfort score (BCS)
timeFrame: 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.
measure: pressing times of PCIA
timeFrame: 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.
measure: The number of patients who required remedial analgesic during the first 48h after operation
timeFrame: Within 48hours after surgery
measure: Frequency of remedial analgesic during the first 48h after operation
timeFrame: Within 48hours after surgery
measure: The cumulative remedial analgesic consumption during the first 48h after operation
timeFrame: Within 48hours after surgery
measure: PONV
timeFrame: 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.
measure: pruritus
timeFrame: 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.
measure: Frequency of remedial antiemetic during the first 48h after operation
timeFrame: Within 48hours after surgery
measure: The cumulative remedial antiemetic consumption during the first 48h after operation
timeFrame: Within 48hours after surgery
measure: Ramsay sedation score
timeFrame: 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.
measure: The number of patients who required remedial antiemetic during the first 48h after operation
timeFrame: Within 48hours after surgery
measure: hypotension
timeFrame: 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.
measure: respiratory depression
timeFrame: 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.
measure: dizziness
timeFrame: 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.
measure: sufentanil
timeFrame: Before leaving PACU(T0). T0 is defined as before the patients leave PACU.
measure: Satisfaction rating
timeFrame: T5 is defined as 48 hour after surgery.
measure: HR
timeFrame: 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.
measure: NBP
timeFrame: 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.
measure: SpO2
timeFrame: 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.
measure: Time for leaving the bed
timeFrame: at discharge (assessed up to day 7)
measure: Time for intestinal movement
timeFrame: at discharge (assessed up to day 7)
measure: Time for drinking
timeFrame: at discharge (assessed up to day 7)
measure: Time for eating
timeFrame: at discharge (assessed up to day 7)
Other outcomes:
Locations:
city: Jinan
country: China
facility: Meng-Lv
state: Shandong
Study officials:
affiliation: Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University
name: Meng Lv, doctor
role: PRINCIPAL_INVESTIGATOR
References: