Comparison of the Effects of Fentanyl, Oxycodone, Butorphanol on Gastrointestinal Function

Study Overview
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Brief Summary
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Postoperative ileus (POI) is a transient loss of coordinated peristalsis precipitated by surgery and exacerbated by opioid pain medication.So,how to provide patients with ideal analgesia without affecting the recovery of postoperative gastrointestinal function?This was a prospective randomized controlled study. A total of 105 patients who were scheduled for laparoscopic hysterectomy were randomly selected from The First Affiliated Hospital with Nanjing Medical University by random number table. These patients were randomly divided into three groups: fentanyl(F) group, oxycodone(O) group and butorphanol(B) group.

Detailed Description
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Background: Patients often experience pain after gynecological laparoscopy. However, the use of opioid analgesia after surgery may increase the incidence of postoperative ileus (POI). Postoperative ileus (POI) is a common surgical emergency after a surgical procedure, leading to infection and intestinal adhesions, which can extend hospitalization and increase readmission rates, and consequently increasing healthcare costs. How to provide patients with ideal analgesia without affecting the recovery of postoperative gastrointestinal function? There is no guideline which has been troubling clinical anesthesiologists. Aims: To observe the effects of fentanyl, oxycodone, Butorphanol on the recovery of gastrointestinal function after laparoscopic hysterectomy. Methods: A total of 105 patients undergoing laparoscopic hysterectomy were randomly divided to three groups: fentanyl group(group F), butorphanol group(group B), or oxycodone group(group O). The primary outcome measures were postoperative time to first anal exhaust the total analgesic doses in PCIA,effective bolus times. Patients were also assessed for pain with a visual analogue scale (VAS), the cumulative PCIA dose, adverse effects (Nausea,vomiting, bradycardia, respiratory depression and pruritus), sedation level at 4, 12, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours and postoperative hospitalization days.

Official Title
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Comparison of the Effects of Fentanyl, Oxycodone, Butorphanol on Gastrointestinal Function in Patients Undergoing Laparoscopic Hysterectomy: a Double-blind, a Randomized Controlled Trial

Conditions
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Cervix Neoplasms, Endometrial Cancer, Adenomyosis, Fibroid Uterus

Intervention / Treatment
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* Drug: the drug of intravenous patient-controlled analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who were scheduled for laparoscopic hysterectomy from W&C BRANCH HOSPITAL OF JIANGSU PROVINCE HOSPITAL American Society of Anesthesiologists (ASA) physical status classification 1 to 2, Women aged 40-65 Weight 50-80 kg Exclusion Criteria: History of opioids abuse and allergy and contraindication to opioid drugs bronchial asthma; coronary heart disease; severe hypertension; diabetes mellitus; hepatic, and renal dysfunction (glutamyl aminotransferase> 40U or aspartate aminotransferase> 35U; urea nitrogen> 8.2 μmol / L, creatinine> 133 μmol / L), History of brain damage or psychiatric disease Patients with coagulopathy (PT> 17 seconds or activated partial thromboplastin time (APTT)> 47 seconds); pregnant or lactating women; Those with long-term constipation; History of digestive diseases; history of gastrointestinal disease (peptic ulcer disease, Crohn's disease, or ulcerative colitis) Participants in other drug trials in the past three months. （11）After randomization and allocation, patients were withdrawn if laparoscopy was converted to open surgery or if they required reinvestigation for postoperative bleeding.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fentanyl group(group F)<br>Fentanyl citrate injection, specification: 10mL: 0.5mg / piece (production unit: niching chang rendu Pharmaceutical Co., Ltd., valid period: 48 months) For group F patients,0.5mg fentanyl was mixed with saline to a total volume of 100mL; continuous infusion was set to 2mL/h, a bolus dose of 3mL, and a lockout interval of 15 minutes | Drug: the drug of intravenous patient-controlled analgesia<br>* At present, opioids are most widely used in postoperative analgesia. This study aims to use different opioid receptor agonists---fentanyl, oxycodone and butorphanol for analgesia after laparoscopic hysterectomy.Compare the recovery of gastrointestinal function after operation.<br>* Other names: intravenous patient-controlled analgesia (IV-PCA);|
| Experimental: Oxycodone group(group O)<br>Oxycodone hydrochloride injection, specification: 1mL: 10mg / branch (production unit: HAMOL LIMITED, valid period: 60 months) For group O patients,30mg oxycodone was mixed with saline to a total volume of 100mL; continuous infusion was set to 2mL/h, a bolus dose of 3mL, and a lockout interval of 15 minutes | Drug: the drug of intravenous patient-controlled analgesia<br>* At present, opioids are most widely used in postoperative analgesia. This study aims to use different opioid receptor agonists---fentanyl, oxycodone and butorphanol for analgesia after laparoscopic hysterectomy.Compare the recovery of gastrointestinal function after operation.<br>* Other names: intravenous patient-controlled analgesia (IV-PCA);|
| Experimental: Butorphanol group(group B)<br>Butorphanol tartrate injection, specification: 1 mL: 1 mg / branch (production unit: Jiangsu henryi Pharmaceutical Co., Ltd., valid period: 24 months); For group B patients,10mg butorphanol was mixed with saline to a total volume of 100mL; continuous infusion was set to 2mL/h, a bolus dose of 3mL, and a lockout interval of 15 minutes | Drug: the drug of intravenous patient-controlled analgesia<br>* At present, opioids are most widely used in postoperative analgesia. This study aims to use different opioid receptor agonists---fentanyl, oxycodone and butorphanol for analgesia after laparoscopic hysterectomy.Compare the recovery of gastrointestinal function after operation.<br>* Other names: intravenous patient-controlled analgesia (IV-PCA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative time to first anal exhaust | Timing from the end of the operation | From date of operation until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 15 days | 
| the cumulative dose administered in the patient-controlled mode | The cumulative dose administered in the patient-controlled mode during the initial 48 hours after the operation was measured | From date of operation until the date of first documented progression of anal exhaust , assessed up to 48 hours | 
| effective bolus times | The effective bolus times in the patient-controlled mode during the initial 48 hours after the operation was measured | From date of operation until the date of first documented progression of anal exhaust , assessed up to 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain score | by using numerical rating scale (NRS):The pain scale ranged from 0 (=no pain) to 10 (=worst pain imaginable) | at 4 hours postoperatively | 
| pain score | by using numerical rating scale (NRS):The pain scale ranged from 0 (=no pain) to 10 (=worst pain imaginable) | at 12 hours postoperatively | 
| pain score | by using numerical rating scale (NRS):The pain scale ranged from 0 (=no pain) to 10 (=worst pain imaginable) | at 24 hours postoperatively | 
| pain score | by using numerical rating scale (NRS):The pain scale ranged from 0 (=no pain) to 10 (=worst pain imaginable) | at 48 hours postoperatively | 
| Sedation score | by using Ramsay scale（1=anxious and agitated or restless, or both; 2=cooperative, oriented, and tranquil; 3=responds to command only; 4=asleep, but has a brisk response to light tactile stimulus or a simple verbal command; 5=asleep, but arousable only by strong physical stimulus; and 6=asleep, unarousable） | at 4 hours postoperatively | 
| Sedation score | by using Ramsay scale（1=anxious and agitated or restless, or both; 2=cooperative, oriented, and tranquil; 3=responds to command only; 4=asleep, but has a brisk response to light tactile stimulus or a simple verbal command; 5=asleep, but arousable only by strong physical stimulus; and 6=asleep, unarousable） | at 12 hours postoperatively | 
| Sedation score | by using Ramsay scale（1=anxious and agitated or restless, or both; 2=cooperative, oriented, and tranquil; 3=responds to command only; 4=asleep, but has a brisk response to light tactile stimulus or a simple verbal command; 5=asleep, but arousable only by strong physical stimulus; and 6=asleep, unarousable） | at 24 hours postoperatively | 
| Sedation score | by using Ramsay scale（1=anxious and agitated or restless, or both; 2=cooperative, oriented, and tranquil; 3=responds to command only; 4=asleep, but has a brisk response to light tactile stimulus or a simple verbal command; 5=asleep, but arousable only by strong physical stimulus; and 6=asleep, unarousable） | at 48 hours postoperatively | 
| adverse effects | Nausea 、vomiting 、bradycardia（HR <60 beats min-1）、respiratory depression(According to practice guidelines from the ASA, clinical signs of opioid-induced respiratory depression are respiratory rate <10 bpm, arterial O2 saturation <90%, or arterial CO2 tension >6.66 kPa) and pruritus | at 4 hours postoperatively | 
| adverse effects | Nausea 、vomiting 、bradycardia（HR <60 beats min-1）、respiratory depression(According to practice guidelines from the ASA, clinical signs of opioid-induced respiratory depression are respiratory rate <10 bpm, arterial O2 saturation <90%, or arterial carbon dioxide (CO2)tension >6.66 kPa) and pruritus | at 12 hours postoperatively | 
| adverse effects | Nausea 、vomiting 、bradycardia（HR <60 beats min-1）、respiratory depression (According to practice guidelines from the ASA, clinical signs of opioid-induced respiratory depression are respiratory rate <10 bpm, arterial O2 saturation <90%, or arterial CO2 tension >6.66 kPa)and pruritus | at 24 hours postoperatively | 
| adverse effects | Nausea 、vomiting 、bradycardia（HR <60 beats min-1）、respiratory depression (According to practice guidelines from the ASA, clinical signs of opioid-induced respiratory depression are respiratory rate <10 bpm, arterial O2 saturation <90%, or arterial CO2 tension >6.66 kPa)and pruritus | at 48 hours postoperatively | 
| patients' degree of overall satisfaction with the postoperative analgesia | Patients were asked to evaluate their degree of overall satisfaction with the postoperative analgesia on a 11-point scale (0= very unsatisfied, 1-3= unsatisfied, 4-6 = neutral, 7-9= satisfied, or 10 = very satisfied). | at 48 hours postoperatively | 
| postoperative hospitalization days | All patients were cured in accordance with clinical cure standard | From date of operation until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 15 days |