Combination of Nalbuphine and Dexmedetomidine Versus Sufentanil and Dexmedetomidine on Patients

Laparoscopic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05445024
• Other study ID #: LM-WWW-2022
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2023
• Source: Qianfoshan Hospital
• Contact: Meng Lv
• Phone: 15169105373
• Email: qylvmeng[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2023
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastrointestinal Surgery
• Laparoscopic

Intervention

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

Locations

Country	Name	City	State
China	Meng-Lv	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Qianfoshan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analogue Scale (VAS) at rest	VAS = a 10 cm VAS for pain (0, no pain; 10, worst imaginable pain)	At 24 hour after operation
Secondary	VAS upon movement	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)	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.
Secondary	VAS at rest	VAS = a 10 cm VAS for pain (0, no pain; 10, worst imaginable pain)	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.
Secondary	VAS at rest	VAS= a 10 cm VAS for pain (0, no pain; 10, worst imaginable pain) at rest	Before leaving post anesthesia care unit (PACU)(T0) .T0 is defined as before the patients leave PACU.
Secondary	Brinell comfort score (BCS)	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.	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.
Secondary	pressing times of PCIA	PCIA(patient controled anesthesia), effective pressing times of PCIA/actual 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.
Secondary	The number of patients who required remedial analgesic during the first 48h after operation	The number of patients who required remedial analgesic such as opioids(demerol,sufentanil,morphine)or non-steroid anti-inflammatory drugs(acetaminophen,diclofenac).	Within 48hours after surgery
Secondary	Frequency of remedial analgesic during the first 48h after operation	Frequency of remedial analgesic during the first 48h after operation	Within 48hours after surgery
Secondary	The cumulative remedial analgesic consumption during the first 48h after operation	The cumulative remedial analgesic consumption such as demerol, sufentanil, morphine	Within 48hours after surgery
Secondary	PONV	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 ? was nausea with mild vomiting. Degree III was severe vomiting requiring further treatment. Grade ? is uncontrollable vomiting.; The total number of episodes of vomiting was recorded.	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.
Secondary	pruritus	0, no; 1, mild; 2, moderate; 3, severe.	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.
Secondary	Frequency of remedial antiemetic during the first 48h after operation	Frequency of remedial antiemetic during the first 48h after operation	Within 48hours after surgery
Secondary	The cumulative remedial antiemetic consumption during the first 48h after operation	The cumulative remedial antiemetic consumption during the first 48h after operation	Within 48hours after surgery
Secondary	Ramsay sedation score	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)	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.
Secondary	The number of patients who required remedial antiemetic during the first 48h after operation	The number of patients who required remedial antiemetic	Within 48hours after surgery
Secondary	hypotension	Hypotension was defined as systolic arterial pressure <90 mmHg at any investigated time or mean artetial pressure (MAP) decreased by 30% from baseline..	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.
Secondary	respiratory depression	Respiratory depression was defined as ventilatory frequency,8 min-1 or hypoxaemia (SpO2<90%).	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.
Secondary	dizziness	0, no; 1, mild; 2, moderate; 3, severe.	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.
Secondary	sufentanil	Sufentanil amount in intraoperative and PACU	Before leaving PACU(T0). T0 is defined as before the patients leave PACU.
Secondary	Satisfaction rating	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)	T5 is defined as 48 hour after surgery.
Secondary	HR	heart rate	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.
Secondary	NBP	noninvasive arterial pressure,	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.
Secondary	SpO2	oxygen saturation	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.
Secondary	Time for leaving the bed	Time for patients to leave the bed and walk	at discharge (assessed up to day 7)
Secondary	Time for intestinal movement	Intestinal movement=The patient passed gas for the first time	at discharge (assessed up to day 7)
Secondary	Time for drinking	Time for drinking= The patient drink water for the first time	at discharge (assessed up to day 7)
Secondary	Time for eating	Time for eating= The patient eat food for the first time	at discharge (assessed up to day 7)