Effect of Intraperitoneal Ropivacaine on Visceral Pain After Laparoscopic Gastrectomy

Ropivacaine Clinical Trial

Official title:

A Randomized Controlled Study of the Effect of Intraperitoneal Ropivacaine on Visceral Pain After Laparoscopic Gastrectomy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06145945
• Other study ID #: 2023ZSLYEC-502
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 25, 2023
• Est. completion date: July 7, 2024

Study information

• Verified date: November 2023
• Source: Sixth Affiliated Hospital, Sun Yat-sen University
• Contact: SanQing Jin, MD
• Phone: 0086-13719366863
• Email: sanqingjin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Visceral pain is obvious and lasts for a long time in patients after laparoscopic gastrectomy.Relieving the visceral pain is of great significance for patients' postoperative emotional experience, functional recovery and reducing the formation of long-term chronic pain. However, there is no clear clinical consensus on relieving visceral pain by now, so effective clinical methods to relieve visceral pain need to be explored urgently.

Intraperitoneal spraying local anesthetics is a simple and inexpensive method, which has been proved to be safe and effective in randomized controlled trials and Meta-analysis of various types of surgery.However, its effect in clinical research is still controversial and many studies lack evaluation of postoperative recovery quality, so it has not been widely used in clinical practice.

This study aims to explore the effect of intraperitoneal spraying ropivacaine (long-acting amide local anesthetic) on visceral pain after laparoscopic gastrectomy, and to systematically evaluate its effect on the recovery of gastrointestinal function and the inflammatory factors (IL-6, TNF-α) in abdominal drainage fluid.

Description:

Postoperative pain is a common adverse reaction after laparoscopic gastrectomy. Insufficient analgesia can cause severe stress response,affect the recovery of postoperative gastrointestinal function, increase the incidence of postoperative complications and prolong the length of hospital stay. Although laparoscopic surgery significantly reduces postoperative pain compared to traditional open surgery, the management of postoperative pain remains a challenge. Postoperative pain after laparoscopic surgery is mainly divided into three parts: incision pain(somatic pain component), deep abdominal pain (visceral pain component) and shoulder pain (referred pain component). In a prospective study, Blichfeldt-Eckhardt et al. found that visceral pain accumulated in the first week after surgery was identified as an independent risk factor for unexplained chronic pain at 12 months after surgery, and visceral pain was the only pain component that was independently and significantly associated with chronic unexplained pain at 12 months after surgery .

Visceral pain is generally defined as pain caused inside the body, but is usually caused by excessive contraction, stretching, or ischemia of the walls of internal organs . In contrast to pain signals originating from the skin,pain originating from the viscera is described as dull and diffuse, often poorly localized, and can be distant from its origin.Visceral pain is considered more unpleasant and frightening than somatic pain.

Therefore,relieving the visceral pain is of great significance for patients' postoperative emotional experience, functional recovery and reducing the formation of long-term chronic pain. However, there is no clear clinical consensus on relieving visceral pain by now, so effective clinical methods to relieve visceral pain need to be explored urgently.

Intraperitoneal spraying local anesthetics is a simple and inexpensive method, which has been proved to be a safe and effective way to reduce the use of opioid and postoperative pain score in randomized controlled trials and Meta-analysis of various surgical types such as laparoscopic cholecystectomy , laparoscopic appendectomy , laparoscopic gynecology and so on. Intraperitoneal spraying local anesthetics is a type of topical anesthesia.Local anesthetics produce local anesthesia by acting on nerve endings on the surface of the visceral organs.Visceral organs mainly transmit nociceptive signals through the vagus nerve and spinal nerve, among which the spinal nerve mainly transmits mechanical stimulation signals, while the vagus nerve mainly transmits chemical stimulation signals. Arman Kahokehr et al. found that intraperitoneal spraying local anesthetics during colectomy may reduce postoperative pain by blocking intra-abdominal vagus nerve signals. At the same time, it inhibits the corresponding neuroendocrine stress pathway, thus resulting in behavioral benefits. However, it does not separately evaluate the different pain components of patients after surgery.

At the same time,the effect of intraperitoneal spraying local anesthetics is still controversial and many studies lack evaluation of postoperative recovery quality,so this technique has not been widely used in clinical practice. Schipper IE et al. spray 20ml 2.5% bupivacaine into the abdominal cavity during laparoscopic gastric bypass surgery, and the test results indicated that the experimental group did not significantly reduce postoperative pain or opioid use, and the use of antiemetic drugs and the length of hospital stay were not significantly reduced.A review in 2021 included 85 clinical trials of intraperitoneal spraying local anesthetics during laparoscopic cholecystectomy, found that intraperitoneal spraying local anesthetics could reduce pain for up to 24 hours in patients undergoing laparoscopic cholecystectomy. However,none of these trials provided postoperation follow-up information and evaluation of postoperative recovery quality.

In this study, pain types are assessed independently to explore whether intraperitoneal spraying local anesthetics could reduce visceral pain by blocking splanchnic nerve afferents. This study will use ropivacaine, the most commonly used long-acting amide local anesthetic, which has low toxicity and an effective acting time of about 4-6 hours.This study set up multiple time points after surgery to evaluate the visceral pain and recovery quality of patients,in order to explore whether early postoperative pain control can slow down or block the formation of postoperative chronic pain, and systematically evaluate the effect of intraperitoneal spraying local anesthetics on the postoperative recovery quality of patients.In a meta-analysis Sparreboom CL et al. found that patients with postoperative anastomotic leakage had significantly higher levels of IL-6 and TNF-α in abdominal drainage fluid at 24h after surgery than those without anastomotic leakage, but this significant change was not observed in blood samples.Wiik et al. reported that inflammatory cytokines are more widely released into the abdominal cavity after abdominal surgery compared with systemic responses,which may be due to the secretion of these cytokines by lymphocytes and monocytes at the site of anastomotic leak.Inflammatory factors are not only related to postoperative anastomotic leakage, but also closely related to the occurrence and development of postoperative pain.Inflammatory stimulation or tissue damage stimulates a cytokine cascade that ultimately triggers the release of mediators that cause inflammatory pain. Immune cells release inflammatory factors such as IL-6 and TNF-α, and induce prostaglandin synthesis and enhance TRP and Nav channel activation through a series of signal transduction pathways, thus inducing inflammatory pain in vivo.Therefore, we plan to detect the inflammatory factors IL-6 and TNF-α in the abdominal drainage fluid at 24h after surgery,to explore the effect of Intraperitoneal spraying local anesthetics on the postoperative abdominal drainage fluid related inflammatory factors, and to evaluate its influence on the recovery of postoperative gastrointestinal function further.

The anesthesia induction protocol for this study includes intravenous titration administration of propofol at a rate of 0.5mg/kg/min, sufentanil 0.3ug/kg, and cisatracurium 0.2mg/kg. Anesthesia is maintained with propofol, remifentanil cisatracurium and sevoflurane to maintain the patient's blood pressure at ±20% of the basic blood pressure and BIS between 40 and 60. The first dose of analgesia and antiemetic (0.3ug/kg sufentanil + 5mg dezocine + 0.25mg palonosetron hydrochloride) is given half an hour before the end of surgery. Before closing the abdominal cavity after abdominal irrigation, 20ml of 0.5% ropivacaine or an equal volume of normal saline is uniformly sprayed onto the surgical area using an endoscopic instrument channel. After skin closure, 10ml of 0.5% ropivacaine is used for infiltration anesthesia at the incision site, and a venous analgesia pump is connected (3ug/kg sufentanil + dezocine 15mg+ palonosetron hydrochloride 0.5mg+NS 120ml). After the surgery, the patient is induced to spontaneous breathe and the tracheal tube will be removed, and then he is sent to the PACU for further observation. If the pain NRS score in the recovery room is greater than 4, a single injection of 5ug sufentanil will be administered until the NRS score is ≤4. When the patient achieve a Sterward score of 6 points, he will be returned to the ward.

Visceral pain is obvious and lasts for a long time in patients after laparoscopic gastrectomy. This study intends to include these patients in the study, and adopt ropivacaine, a local anesthetic with less cardiotoxicity and relatively long acting time,to provide further clinical data for the relief of postoperative visceral pain by intraperitoneal spraying local anesthetics.This study will also systematically evaluate the effect of intraperitoneal spraying local anesthetics on the postoperative recovery quality and the inflammatory factors in postoperative abdominal drainage fluid.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 72
• Est. completion date: July 7, 2024
• Est. primary completion date: March 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age 18-65 years old

2. The American Society of Anesthesiologists(ASA) grade is I or II, and the heart function grade is 1-2;

3. Elective laparoscopic gastrectomy under general anesthesia

Exclusion Criteria:

1. Patients have severe heart, lung, liver, and kidney diseases (heart function grade>3 / respiratory failure / liver failure / renal failure)

2. BMI<18kg/m2 or >30kg/m2

3. Patients with chronic pain other than stomach pain and taking analgesics for a long time

4. Patients with history of allergy to local anesthetics

5. Patients with high risk of reflux and aspiration such as digestive obstruction

6. Patients who refuse to participate or don't sign or refuse to sign the informed consent form

7. Patients who are unable to communicate effectively

8. Patients participate in other clinical trials

Related Conditions & MeSH terms

• Laparoscopic Gastrectomy
• Ropivacaine
• Visceral Pain

Intervention

Drug:
• 0.5% Ropivacaine
20ml 0.5% ropivacaine is sprayed intraperitoneally
• Saline
20ml saline is sprayed intraperitoneally

Locations

Country	Name	City	State
China	SanQing Jin	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
SanQing Jin

Country where clinical trial is conducted

China, 

References & Publications (18)

Blichfeldt-Eckhardt MR, Ording H, Andersen C, Licht PB, Toft P. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy. Pain. 2014 Nov;155(11):2400-7. doi: 10.1016/j.pain.2014.09.019. Epub 2014 Sep 22. — View Citation

Boezaart AP, Smith CR, Chembrovich S, Zasimovich Y, Server A, Morgan G, Theron A, Booysen K, Reina MA. Visceral versus somatic pain: an educational review of anatomy and clinical implications. Reg Anesth Pain Med. 2021 Jul;46(7):629-636. doi: 10.1136/rapm-2020-102084. — View Citation

Cha SM, Kang H, Baek CW, Jung YH, Koo GH, Kim BG, Choi YS, Cha SJ, Cha YJ. Peritrocal and intraperitoneal ropivacaine for laparoscopic cholecystectomy: a prospective, randomized, double-blind controlled trial. J Surg Res. 2012 Jun 15;175(2):251-8. doi: 10.1016/j.jss.2011.04.033. Epub 2011 May 17. — View Citation

Fang D, Kong LY, Cai J, Li S, Liu XD, Han JS, Xing GG. Interleukin-6-mediated functional upregulation of TRPV1 receptors in dorsal root ganglion neurons through the activation of JAK/PI3K signaling pathway: roles in the development of bone cancer pain in a rat model. Pain. 2015 Jun;156(6):1124-1144. doi: 10.1097/j.pain.0000000000000158. — View Citation

Feng B, Guo T. Visceral pain from colon and rectum: the mechanotransduction and biomechanics. J Neural Transm (Vienna). 2020 Apr;127(4):415-429. doi: 10.1007/s00702-019-02088-8. Epub 2019 Oct 9. — View Citation

Gebhart GF, Bielefeldt K. Physiology of Visceral Pain. Compr Physiol. 2016 Sep 15;6(4):1609-1633. doi: 10.1002/cphy.c150049. — View Citation

Gudes S, Barkai O, Caspi Y, Katz B, Lev S, Binshtok AM. The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-alpha-mediated increase in nociceptors excitability. J Neurophysiol. 2015 Jan 15;113(2):601-19. doi: 10.1152/jn.00652.2014. Epub 2014 Oct 29. — View Citation

Kahokehr A, Sammour T, Zargar Shoshtari K, Taylor M, Hill AG. Intraperitoneal local anesthetic improves recovery after colon resection: a double-blinded randomized controlled trial. Ann Surg. 2011 Jul;254(1):28-38. doi: 10.1097/SLA.0b013e318221f0cf. — View Citation

Kang H, Kim BG. Intraperitoneal ropivacaine for effective pain relief after laparoscopic appendectomy: a prospective, randomized, double-blind, placebo-controlled study. J Int Med Res. 2010 May-Jun;38(3):821-32. doi: 10.1177/147323001003800309. — View Citation

Koenen LR, Icenhour A, Forkmann K, Pasler A, Theysohn N, Forsting M, Bingel U, Elsenbruch S. Greater fear of visceral pain contributes to differences between visceral and somatic pain in healthy women. Pain. 2017 Aug;158(8):1599-1608. doi: 10.1097/j.pain.0000000000000924. — View Citation

Malsch P, Andratsch M, Vogl C, Link AS, Alzheimer C, Brierley SM, Hughes PA, Kress M. Deletion of interleukin-6 signal transducer gp130 in small sensory neurons attenuates mechanonociception and down-regulates TRPA1 expression. J Neurosci. 2014 Jul 23;34(30):9845-56. doi: 10.1523/JNEUROSCI.5161-13.2014. — View Citation

Ruiz-Tovar J, Gonzalez J, Garcia A, Cruz C, Rivas S, Jimenez M, Ferrigni C, Duran M. Intraperitoneal Ropivacaine Irrigation in Patients Undergoing Bariatric Surgery: a Prospective Randomized Clinical Trial. Obes Surg. 2016 Nov;26(11):2616-2621. doi: 10.1007/s11695-016-2142-z. — View Citation

Rutherford D, Massie EM, Worsley C, Wilson MS. Intraperitoneal local anaesthetic instillation versus no intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD007337. doi: 10.1002/14651858.CD007337.pub4. — View Citation

Schipper IE, Schouten M, Yalcin T, Algie GD, Damen SL, Smeenk RM, Schouten R. The Use of Intraperitoneal Bupivacaine in Laparoscopic Roux-en-Y Gastric Bypass: a Double-blind, Randomized Controlled Trial. Obes Surg. 2019 Oct;29(10):3118-3124. doi: 10.1007/s11695-019-03982-6. — View Citation

Sparreboom CL, Wu Z, Dereci A, Boersema GS, Menon AG, Ji J, Kleinrensink GJ, Lange JF. Cytokines as Early Markers of Colorectal Anastomotic Leakage: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2016;2016:3786418. doi: 10.1155/2016/3786418. Epub 2016 Mar 9. — View Citation

Wiik H, Karttunen R, Haukipuro K, Syrjala H. Maximal local and minimal systemic cytokine response to colorectal surgery: the influence of perioperative filgrastim. Cytokine. 2001 May 7;14(3):188-92. doi: 10.1006/cyto.2001.0870. — View Citation

Yong L, Guang B. Intraperitoneal ropivacaine instillation versus no intraperitoneal ropivacaine instillation for laparoscopic cholecystectomy: A systematic review and meta-analysis. Int J Surg. 2017 Aug;44:229-243. doi: 10.1016/j.ijsu.2017.06.043. Epub 2017 Jun 30. — View Citation

Zarbock A, Ley K. Neutrophil adhesion and activation under flow. Microcirculation. 2009 Jan;16(1):31-42. doi: 10.1080/10739680802350104. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NRS scores of visceral pain	NRS scores of visceral pain at 24 hours after surgery	24 hours after surgery
Secondary	NRS scores of visceral pain	NRS scores of visceral pain at 0 hour,1 hour,6 hours,12 hours,the second day,the third day and the 30th day after surgery	From surgery completion to the 30th day after surgery
Secondary	NRS scores of incisional pain	NRS scores of incisional pain at 0 hour,1 hour,6 hours,12 hours,24 hours,the second day,the third day and the 30th day after surgery	From surgery completion to the 30th day after surgery
Secondary	NRS scores of referred pain	NRS scores of referred pain at 0 hour,1 hour,6 hours,12 hours,24 hours,the second day,the third day and the 30th day after surgery	From surgery completion to the 30th day after surgery
Secondary	Blood pressure(SBP,DBP,MAP)	Relative change of blood pressure(SBP,DBP,MAP) at the time of entering the operating room,the beginning of anesthesia,the beginning of surgery and 0 hour,1 hour,6 hours,12 hours,24 hours,the second day,the third day after surgery	From the period of anesthesia to the third day after surgery
Secondary	Heart rate	Relative change of heart rate at the time of entering the operating room,the beginning of anesthesia,the beginning of surgery and 0 hour,1 hour,6 hours,12 hours,24 hours,the second day,the third day after surgery	From the period of anesthesia to the third day after surgery
Secondary	Oxygen saturation	Relative change of oxygen saturation at the time of entering the operating room,the beginning of anesthesia,the beginning of surgery and 0 hour,1 hour,6 hours,12 hours,24 hours,the second day,the third day after surgery	From the period of anesthesia to the third day after surgery
Secondary	Additional analgesics in the ward	Use of additional analgesics in the ward	From surgery completion to the third day after surgery
Secondary	Nausea and vomiting	Whether nausea and vomiting, the frequency of vomiting	From surgery completion to the third day after surgery
Secondary	Use of intravenous analgesia pump	The total and effective pressing times of intravenous analgesia pump,total consumption of sufentanil	From surgery completion to the third day after surgery
Secondary	Serum C-reactive protein (CRP) concentration	Serum C-reactive protein (CRP) concentration	One day before surgery and 24 hours after surgery
Secondary	The level of blood glucose	The level of blood glucose	One day before surgery and 24 hours after surgery
Secondary	Interleukin-6(IL-6)	IL-6 concentration in abdominal drainage fluid	24 hours after surgery
Secondary	Tumor necrosis factor-a(TNF-a)	TNF-a concentration in abdominal drainage fluid	24 hours after surgery
Secondary	Postoperative recovery score using 15-item quality of recovery scoring system(QoR-15)	To evaluate the postoperative recovery using 15-item quality of recovery scoring system including emotional state,body comfort, psychological support, body independence and pain at the first day,the second day,the third day and the 30th day after surgery	From the first day to the 30th day after surgery
Secondary	Anal exhaust time	The time of first anal exhaust time after surgery	From surgery completion to first anal exhaust after surgery,assessed up to 7 days
Secondary	Sitting up time	The time of first sitting up time after surgery	From surgery completion to first sitting up after surgery,assessed up to 7 days
Secondary	Getting out of bed time	The time of first getting out of bed time after surgery	From surgery completion to first getting out of bed after surgery,assessed up to 7 days
Secondary	First drinking time after surgery	First drinking time after surgery	From surgery completion to first drinking after surgery,assessed up to 7 days
Secondary	First eating time after surgery	First eating time after surgery	From surgery completion to first eating after surgery,assessed up to 7 days
Secondary	Removal of stomach tube time	Removal of stomach tube time	From surgery completion to removal of stomach tube,assessed up to 30 days
Secondary	Removal of drainage tube time	Removal of drainage tube time	From surgery completion to removal of drainage tube,assessed up to 30 days
Secondary	Removal of indwelling urinary catheter time	Removal of indwelling urinary catheter time	From surgery completion to removal of indwelling urinary catheter,assessed up to 30 days
Secondary	Incidence of postoperative complications within 30 days after surgery	Incidence of intra-abdominal infection and anastomotic leakage within 30 days after surgery	Within 30 days after surgery
Secondary	Length of hospital stay after surgery	Hospital stay time from operation completion to actual hospital discharge	From surgery completion to actual hospital discharge, assessed up to 30 days