Anrikefon, Laparoscopic Surgery, Patient-controlled Intravenous Analgesia, Visceral Pain, Postoperative
Conditions
Keywords
Laparoscopic surgery, Visceral pain, Postoperative, Anrikefon, Patient-controlled intravenous analgesia
Brief summary
Visceral pain following laparoscopic surgery is frequently underestimated, yet it is associated with a range of adverse outcomes. Effective visceral pain management should constitute an essential component of postoperative analgesic strategies following laparoscopic procedures. However, conventional analgesic agents, including μ-opioid receptor agonists, lack specificity for visceral pain. Anrikefon, a novel selective peripheral κ-opioid receptor agonist, demonstrates unique efficacy in alleviating visceral pain with a favorable safety profile. Preliminary studies showed that a single intravenous dose of anrikefon effectively alleviates postoperative pain after abdominal surgery with a low risk of adverse effects. The investigators hypothesize that an appropriate dosing regimen of anrikefon administered via patient-controlled intravenous analgesia (PCIA) pump, as part of a multimodal analgesic strategy, can specifically target and alleviate visceral pain after laparoscopic surgery, thereby achieving comprehensive postoperative analgesia.
Detailed description
Approximately 50% to 90% of patients undergoing abdominal surgery experience moderate or severe acute postoperative pain, which primarily comprises somatic, visceral, and inflammatory pain components, with peak intensity typically occurring within the first 24 to 72 hours after surgery. Inadequate management of acute postoperative pain not only increases patients' suffering and impairs their sleep quality, but also increases the risk of postoperative complications, delays postsurgical recovery, prolongs hospital stay, elevates healthcare costs, and even contributes to the development of chronic neuropathic pain. With advances in minimally invasive techniques and the widespread application of laparoscopic surgery, surgical incisions on the body surface have been significantly reduced, leading to diminished somatic pain. However, the intra-abdominal visceral injury is not necessarily reduced and can even be more substantial in this context, leading to prominent postoperative visceral pain that perioperative clinicians often underestimate. Consequently, effective management of visceral pain should be an essential component of postoperative analgesic strategies following laparoscopic procedures. Opioids, renowned for their potent analgesic efficacy, serve as the cornerstone of perioperative acute pain management and constitute a critical element of multimodal analgesic regimens. Nevertheless, due to the sparse expression of μ-opioid receptors in visceral pain pathways and their weak modulation of visceral pain afferent signaling, the conventional μ-opioid receptor agonists, such as morphine, exhibit limited effectiveness against visceral pain. Anrikefon is a novel selective peripheral κ-opioid receptor agonist. Due to the high expression levels of κ-opioid receptors within visceral pain pathways, anrikefon exerts an unique therapeutic effect in alleviating visceral pain with a relatively low risk of adverse effects. Preliminary studies indicate that a single intravenous dose of Anrikefon effectively alleviates pain after abdominal surgery with a low incidence of adverse effects. Additional evidence suggests that patient-controlled intravenous administration of anrikefon provides effective analgesia after orthopedic surgery without respiratory depression or other severe adverse effects. However, the appropriate dosing regimen of anrikefon for patient-controlled intravenous analgesia (PCIA) following laparoscopic surgery remains to be established. The investigators hypothesize that administering appropriate doses of anrikefon via PCIA pump, as part of a multimodal analgesic regimen that comprises regional nerve blocks targeting somatic pain and nonsteroidal anti-inflammatory drugs (NSAIDs) targeting inflammatory pain, will specifically and effectively alleviate visceral pain following laparoscopic surgery. This pilot trial aims to explore the preliminary efficacy and optimal dosing regimen of anrikefon administered via PCIA after laparoscopic surgery, assess the feasibility of conducting a larger-scale randomized controlled trial, and provide essential parameters for sample size estimation in subsequent investigations.
Interventions
Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises anrikefon (10 μg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.
Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises anrikefon (7.5 μg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.
Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises anrikefon (5 μg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.
DRUGMorphine
Patients in this group receive postoperative patient-controlled intravenous analgesia for 48 hours. The formula comprises morphine (0.5 mg/ml), diluted with normal saline to 100 ml. The analgesic pump is set to deliver an initial loading dose of 8 ml, followed by patient-controlled boluses of 4 ml with a 10-minute lockout interval and no background infusion.
Sponsors
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Aged ≥ 18 years but \< 75 years; 2. Scheduled to undergo elective laparoscopic gastrointestinal surgery with an expected duration of ≥1 hour; 3. The incisional pain can be covered by the transversus abdominis plane block or rectus sheath block; yet patients still require postoperative patient-controlled intravenous analgesia.
Exclusion criteria
1. Presence of preoperative cognitive impairment (Mini-Mental State Examination \[MMSE\] score \< 27), or inability to communicate due to language barrier; 2. Body mass index (BMI) \> 30 kg/m² or \< 18 kg/m²; 3. Presence of poorly controlled or untreated comorbidities, including but not limited to the following: hypertension characterized by a resting systolic blood pressure (SBP) \> 180 mmHg and/or diastolic blood pressure (DBP) \> 110 mmHg, coronary artery disease with unstable angina or myocardial infarction within 6 months, heart failure rated as New York Heart Association classification ≥ III, severe chronic obstructive pulmonary disease (or in a state of acute exacerbation), severe hepatic insufficiency (Child-Pugh grade C), severe renal insufficiency (estimated glomerular filtration rate \< 30 ml/min/1.73m²), or American Society of Anesthesiologists (ASA) physical status classification ≥ IV; 4. Continuous use of opioid analgesics for more than 10 days for any reason, or alcohol abuse (average daily intake of pure alcohol \> 36 g) within 3 months before screening; 5. Preoperative use of opioid or non-opioid analgesics with the interval between the last administration and randomization shorter than five half-lives of the drug or the duration of drug action (whichever is longer); 6. Known allergies or contraindications to opiates or other medications that may be used in this study, such as anesthetics, antiemetics, and nonsteroidal anti-inflammatory drugs (NSAIDs); 7. Anticipated need for postoperative mechanical ventilation； 8. Other conditions that are considered unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted sum of pain intensity difference (SPID) of movement-evoked visceral pain within 48 hours | Within 48 hours after intervention. | Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). Movement-evoked visceral pain intensity will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted SPID of visceral pain at rest within 48 hours | Within 48 hours after intervention. | Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). The intensity of visceral pain at rest will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain). |
| Time-weighted SPID of movement-evoked somatic pain within 48 hours | Within 48 hours after intervention. | Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). Movement-evoked somatic pain intensity will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain). |
| Time-weighted SPID of somatic pain at rest within 48 hours | Within 48 hours after intervention. | Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). The intensity of somatic pain at rest will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain). |
| Time-weighted SPID of movement-evoked overall pain within 48 hours | Within 48 hours after intervention. | Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). Movement-evoked overall pain intensity will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain). |
| Time-weighted SPID of overall pain at rest within 48 hours | Within 48 hours after intervention. | Time-weighted SPID is defined as the cumulative sum of the product obtained by multiplying the pain intensity difference at each time point (calculated by subtracting the baseline pain intensity score from the current pain intensity score) by the time difference (the current time point minus the previous time point). The intensity of overall pain at rest will be assessed before intervention and at 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after intervention using an 11-point Numeric Rating Scale (0 = no pain, 10 = the worst pain). |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORDong-Xin Wang, MD, PhD
Peking University First Hospital
Outcome results
None listed