There have been many studies on the risk factors for long-term postoperative opioid use [11,12,13], but the factors influencing short-term postoperative opioid consumption have not been well studied. To more accurately determine the postoperative opioid needs of patients, we selected patients who used IV-PCA sufentanil at least 48 h after surgery as the subjects for the study. Other administration methods, such as oral administration or single intravenous injection, do not necessarily reflect patients’ real demand for opioids after surgery.
We found that the dosage of opioids after hepatectomy varied considerably among individuals in APS ward rounds. It is generally believed that postoperative pain affects the use of opioids , but there are many influencing factors that deserve further exploration. In this study, we found that an age ≤ 60 years, major hepatic resection, an open approach and a prolonged operation were likely to increase sufentanil consumption 48 h after hepatectomy. Understanding the risk factors for postoperative opioid use will help identify high-risk patients early, allowing us to make the necessary interventions to manage postoperative pain effectively. For high-risk patients, we should conduct close postoperative pain monitoring and increase the use of opioids, or we should appropriately reduce the use of opioids after surgery to avoid wasting these drugs.
In this study, we found that the dosage of sufentanil 48 h after hepatectomy was related to age. The use of opioids after surgery was higher in younger patients than in those who were older. This finding is consistent with the results of most previous studies [15,16,17]. Glasson et al. found that patients aged 54 years or less were more likely to use high-dose opioid analgesics than patients aged 55 or greater . Similarly, Yen et al. and Lin et al. found that patients younger than 60 years received higher doses of opioid analgesics than those aged over 60 [16, 17].
How age affects postoperative opioid dosage is mainly considered as follows: First, older patients are more sensitive to opioid analgesics than younger patients . Second, pharmacokinetic changes with age, including decreased volume of distribution, decreased metabolic function, and decreased elimination rate [19, 20], result in increased accumulation of opioids in elderly patients and prolonged effect intensity and duration. In addition, Kulkarni et al.  believe that young patients may experience greater emotional distress in the context of diseases that require surgery. Compared with young patients, elderly patients may regard serious diseases as the expected pain of aging. Such emotional upheavals, accompanied by symptoms of anxiety and depression, may exacerbate the severity of pain or disrupt healthy behaviors that may reduce pain symptoms. These emotional factors can also have a significant impact on postoperative pain. In general, the correlation between age and postoperative opioid use is generally recognized.
In this study, we found that the surgical approach was an influential factor for postoperative sufentanil dosage, suggesting a reduction in opioid dosage after laparoscopic surgery, which is consistent with the conclusions of many previous studies [22,23,24]. Mala T et al. found that patients undergoing laparoscopic hepatectomy used opioids for an average of 1 day, while patients undergoing open surgery used opiates for an average of 5 days .
A low demand for opioid treatment after laparoscopic surgery is related to a low degree of postoperative pain stress . Since the incisions made in laparoscopic hepatectomy are small and only 4–5 holes need to be established, there is less pain stimulation [26,27,28,29]. Moreover, the local incision infiltration analgesia method can significantly reduce incisional pain and substantially reduce opioid use after surgery .
Additionally, the use of ultrasonic dissection in laparoscopic surgery significantly reduces smoke and eschar formation, fully ensuring that the surgeon has a clear visual field, and ultrasonic dissection does not damage the surrounding healthy tissues [31, 32]. Second, a harmonic scalpel, which is used to free the intrahepatic bile duct and blood vessels during laparoscopic surgery, can use electrocoagulation or clamping according to the thickness of the vessel for greater efficiency. Compared with tools in traditional open surgery, the use of a harmonic scalpel avoids the frequent replacement of other hand instruments and, at the same time, better guarantees electrocoagulation and hemostasis [31, 32]. These factors can significantly reduce pain stress and the need for opioids after surgery.
Studies have found that the extent of resection is an independent influencing factor for postoperative pain. Major hepatectomy is very traumatic, and most of it is performed through laparotomy . During the operation, it is often necessary to use a liver retractor to pull the ribs, and sometimes it is necessary to remove the xiphoid process to fully expose the lesion . Postoperative drainage tubes often lead to severe postoperative pain in patients. This is the main reason for the increased consumption of sufentanil after surgery.
This study found that the operation time was a risk factor for a high postoperative sufentanil dosage. Patients with operation times longer than 300 min consumed more sufentanil within 48 h after the operation, but few related studies have investigated this factor. Loriga B et al.  found that the operation time was a significant risk factor for postoperative pain after vitreoretinal surgery, and this conclusion was related to the choice of anesthesia. Local anesthesia can enhance this correlation because with increases in the operation time and decreases in the anesthetic effect, postoperative pain stimulation increases. Silins V et al.  found that the operation time was an independent predictor for increased morphine consumption in children three days after the operation. It is believed that the operation time might be related to invasiveness, reflecting the degree of activity. Indeed, the liver is rich in blood vessels and has a complex anatomy, and the long operation could reflect the degree of trauma. The longer the operation, the stronger the inflammatory response caused by the inflammatory factors released from the injury, the higher the pain stress, and the greater the demand for opioid drugs after the operation. Unfortunately, the perioperative levels of leukocytes and other inflammatory indices were not included in this study, which could have helped determine the relationship between the duration of surgery and postoperative sufentanil dosage.
Opioid metabolism and clearance are affected by liver and renal function, but in this study, no relationship between perioperative liver and renal function and postoperative sufentanil dosage was found. Sufentanil is metabolized to normethyl sufentanil in liver microsomes, and the activity of normethyl sufentanil is only 10% that of sufentanil . Renal function has a weak effect on the pharmacokinetics of sufentanil , which may be the main reason for these findings; of course, this requires further studies with large samples and multiple centers.
Sex has not been identified in previous studies as an influential factor for postoperative analgesic dosage consistency . Many research studies have reported that women are more likely than men to suffer postoperative pain and use more analgesic drugs [40, 41]. Zheng H et al. found that women used 25.8% more opioids than men within 24 h after surgery . It is generally concluded in many studies that women tend to report higher levels of anxiety and to exhibit factors associated with pain [40, 41]. However, the current study is consistent with that conducted by Lin et al., in that no effect of sex on postoperative sufentanil consumption was found .
Similar to the study by Lee Y et al., the present study did not find that BMI was a risk factor for sufentanil dosage 48 h after surgery . However, studies have shown that BMI is positively correlated with opioid consumption, but the etiology is still unclear [42, 43]. Kvarda P et al. considered that this finding might be related to the bias of surgeons against the use of opioids in obese patients because surgeons believed that patients with higher BMIs metabolized opioids differently and therefore used more analgesics in obese patients . Previous studies on the relationship between these factors and postoperative opioid dosage are few, and further prospective studies are needed.
Similarly, this study did not find that PONV was a factor influencing the postoperative sufentanil dosage, although the postoperative sufentanil dosage was higher in the PONV group. The incidence of nausea and vomiting, in addition to opioid use, would also be affected by many factors, including the type of patient, surgery, and anesthesia [44, 45].
A recent meta-analysis of randomized controlled trials showed that dexmedetomidine saves opioids and can significantly reduce their dosage . Studies have demonstrated that anti-inflammatory and analgesic drugs (e.g., NSAIDs), such as parexib or flurbiprofen, can reduce postoperative pain and reduce postoperative opioid use [47, 48]. However, no effect of intraoperative dexmedetomidine and postoperative NSAID use on the postoperative sufentanil dosage was found in this study. In our study, we also did not find an association between intraoperative blood loss, preoperative platelet count, prothrombin time, or tumor factors and the 48-h postoperative sufentanil dose. There have been few studies on the relationship between these factors and postoperative opioid dosage, and further prospective studies are needed.
This study has several limitations. The design and outcome reliability of retrospective studies is inherently dependent on the accuracy and completeness of the documents available in electronic medical records and surgical reports. The present sample included 562 patients after hepatectomy. As a result, the sample size may not be sufficient to identify the effects of individual variables. Therefore, it is suggested that a larger sample size be studied in the future. In addition, this was a retrospective study that did not confirm the difference between the doses of different opioid analgesics. Future studies should include treatment with other opioids. Postoperative pain and opioid consumption are also influenced by a patient’s psychological factors, the preoperative experience of pain, and the preoperative use of opioids [49,50,51]. It is difficult to evaluate these factors accurately in retrospective investigations; therefore, to comprehensively assess the factors affecting postoperative opioid dosage, it is necessary to add these predictive factors to future prospective studies.
Finally, patient education level and cognitive ability, postoperative infection, postoperative rehabilitation exercise, and other factors may be related to acute postoperative pain and opioid requirements, which can be further explored by adding corresponding observational indicators in future studies.