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.
Aged >= 18 years but < 75 years;
Scheduled to undergo elective laparoscopic colorectal surgery with an expected duration of >=1 hour;
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.
Presence of preoperative cognitive impairment (Mini-Mental State Examination [MMSE] score < 27), or inability to communicate due to language barrier;
Body mass index (BMI) > 30 kg/m² or < 18 kg/m²;
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;
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;
Parallel
High-dose anrikefon
DrugPatients 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.
Medium-dose anrikefon
DrugPatients 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.
Low-dose anrikefon
DrugPatients 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.
Morphine
DrugPatients 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.
Area under curve (AUC) of visceral pain intensity with movement within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Visceral pain intensity with movement will be assessed at 0, 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).
AUC of visceral pain intensity at rest within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Visceral pain intensity at rest will be assessed at 0, 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).
AUC of overall pain intensity with movement within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Overall pain intensity with movement will be assessed at 0, 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).
AUC of overall pain intensity at rest within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Overall pain intensity at rest will be assessed at 0, 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).
Quality of recovery at 24 hours after surgery
Quality of postoperative recovery is assessed using the 15-item Quality of Recovery (QoR-15) scale, a patient-reported questionnaire that evaluates recovery after anesthesia and surgery across five domains: physical comfort, emotional state, psychological support, pain, and activities of daily living. The total score ranges from 0 to 150, with higher scores indicating better quality of postoperative recovery.
Rate of rescue analgesia within 48 hours after intervention
The proportion of patients who require supplemental analgesics.
AUC of somatic pain intensity at rest within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Somatic pain intensity at rest will be assessed at 0, 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).
AUC of somatic pain intensity with movement within 48 hours
The AUC of pain intensity is calculated by summing the trapezoidal areas under the pain intensity data points between each pair of consecutive observations within 48 hours after intervention. Somatic pain intensity with movement will be assessed at 0, 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).
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