Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate, significantly contributing to the global cancer burden (1–5). Most patients are diagnosed in the middle to advanced stages, missing the optimal window for surgery and subsequently requiring chemotherapy (6, 7). Hepatic artery infusion chemotherapy (HAIC) is an effective treatment for unresectable HCC (8–10). Recently, the FOLFOX combination strategy, which includes folinic acid (FnA), 5-fluorouracil (5-FU), and oxaliplatin (OXA), has become prominent in HAIC, significantly enhancing the tumor response rate and patient survival rate for middle and advanced liver cancer (11–14). However, many HCC patients undergoing HAIC experience substantial pain due to arterial spasms caused by the continuous infusion of chemotherapy drugs (15–17). This often leads to the suspension of treatment, negatively affecting therapeutic outcomes. To enhance the quality of life and the effectiveness of HAIC treatment, various interventions, such as non-steroidal anti-inflammatory drugs, opioids, intramuscular anti-spasmolytics, and intra-arterial lidocaine injections, are commonly used in clinical practice (16, 18), despite their limited analgesic efficacy and the potential need for repetitive use.

Lidocaine is the predominant anesthetic used in HAIC, administered through arterial or intravenous routes to provide analgesia (16, 19). However, challenges such as dilution by hepatic artery and the liver microenzyme-mediated degradation of lidocaine to the intermediate metabolite monoethyl glycine xylene pose limitations, resulting in a relatively short-lived analgesic effect (16, 20). To improve patient comfort during surgery and ensure the smooth progression of HAIC treatment, prolonging the analgesic effect is a key clinical objective.

Our study reveals that hepatic artery infusion of lidocaine significantly reduces intraoperative and postoperative pain in HCC patients undergoing HAIC, providing a satisfactory analgesic effect. The details of our findings are presented in the following report.

Approximately 90% of the blood supply to liver cancer tissue is derived from the hepatic artery (21). HAIC allows the continuous infusion of high-concentration cytotoxic drugs directly into tumors, maximizing their lethal effect while minimizing the distribution of chemotherapy drugs to other organs (22, 23). This approach produces potent anti-tumor effects, reduces systemic side effects, and significantly improves the overall survival of patients with liver cancer (24). The FOLFOX regimen, based on OXA, is an approved systemic chemotherapy regimen for advanced liver and colorectal cancer, demonstrating survival benefits in patients with advanced cancer (22).

The lethal effect of chemotherapy drugs on tumor cells may induce a local inflammatory response leading to pain. OXA-induced peripheral neuropathy is a common and sometimes treatment-limiting side effect (25). In clinical practice, during HAIC with OXA for HCC patients, severe abdominal pain, nausea, and vomiting resulting from vasospasm and other adverse reactions can occur, leading to treatment discontinuation. Studies have also suggested that the diameter of the hepatic artery contributes to abdominal pain during HAIC, particularly when the catheter is used for drug infusion (16).

In our study, we found no statistically significant factors affecting pain scores, such as OXA preparation and hepatic artery diameter. During HAIC perfusion, a 100 mg lidocaine infusion through the three-way tube showed a noticeable intraoperative analgesic effect, likely due to reduced nociceptive stimulation from chemotherapy drugs and effective inhibition of central or peripheral nerve sensitization.

Lidocaine, a local anesthetic, is known for its fast, potent, and long-lasting effects, as well as its wide safety range. In the arterial system, lidocaine acts as a potent vasodilator, particularly relaxing highly strained vascular smooth muscle (26). Studies have confirmed that injecting 100 mg of lidocaine through the hepatic artery before embolization effectively relieves intraoperative pain (12). The mechanism behind intraarterial lidocaine's analgesic effect may involve local effects from diffusion into the vascular wall and hepatic parenchyma, endovascular surface anesthesia, and direct vasodilation. This effect can be prolonged by blocking tumor blood supply and slowing drug clearance (12, 27). Previous studies have demonstrated that intra-arterial lidocaine injection is an effective method in most patients (96%, 361 of 376) (16). However, direct injection of lidocaine through the hepatic artery has limitations, resulting in reduced analgesic efficacy and shortened duration due to blood scour and dilution. In comparison to the direct intra-arterial injection method, we used an electronic pump to infuse 100 mg lidocaine through the hepatic artery. Compared to the control group, the study group exhibited favorable changes in preoperative, intraoperative, and postoperative vital signs, VAS, and GCQ scores. Results indicated lower VAS scores in the study group at Time point 01–04 compared to the control group, with post-treatment VAS scores lower than pre-treatment scores. No cases in the study group required supplementary morphine for analgesia, while some patients in the control group needed morphine for pain relief. Lidocaine infused through the hepatic artery significantly reduced intraoperative pain and provided prolonged postoperative analgesia. Additionally, patients in the study group reported higher satisfaction and comfort levels than those in the control group (P < 0.05), affirming the positive analgesic effects of hepatic artery lidocaine infusion and its suitability for clinical promotion.

Furthermore, our results indicated that increasing the lidocaine dose in patients with low pain tolerance was effective, maintaining stable vital signs without adverse events (20). Nevertheless, the maximum effective and safe dose of lidocaine pumped through the hepatic artery during HAIC operations requires further investigation.

In conclusion, lidocaine infusion through the hepatic artery during HAIC effectively reduces intraoperative and postoperative pain and improves patient satisfaction with pain management, making it a valuable technique for clinical practice.