Routine Use of Intravenous Acetaminophen Safely Enhances Pain Control After Minimally Invasive Hepatectomies: a retrospective cohort study

Routine Use of Intravenous Acetaminophen Safely Enhances Pain Control After Minimally Invasive Hepatectomies: a retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Routine Use of Intravenous Acetaminophen Safely Enhances Pain Control After Minimally Invasive Hepatectomies: a retrospective cohort study Kei Furuya, Masao Nakajima, Yukio Tokumitsu, Yoshitaro Shindo, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6533986/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Surgery → Version 1 posted 12 You are reading this latest preprint version Abstract Background Effective postoperative pain management is crucial after minimally invasive hepatectomy (MIH) to promote recovery, and multimodal analgesia strategies are used to reduce opioid requirements and improve outcomes. Multimodal therapies for postoperative pain management commonly comprise acetaminophen. However, the safety and efficacy of acetaminophen for postoperative analgesia in minimally invasive hepatectomy remains unestablished due to its hepatic metabolism. This study aimed to evaluate the safety and analgesic efficacy of routine intravenous acetaminophen administration following MIH. Methods The data of consecutive 50 participants who had undergone MIH were retrospectively analyzed. Regarding postoperative analgesia, participants were assigned to either the opioid-alone cohort (Cohort O) or opioid with routine intravenous acetaminophen cohort (Cohort A). Analgesic efficacy was evaluated using the numerical rating scale (NRS) over the first 2 postoperative days. The sum of opioid rescue doses and frequency of postoperative nausea and vomiting (PONV) were assessed. Analgesic safety was determined by monitoring prolonged elevated transaminase levels. Results Postoperatively, no statistically significant differences in the hepatic and renal functions and systemic inflammatory markers were observed between the two cohorts. On both postoperative day 1 and day 2, Cohort A showed lower NRS scores compared with Cohort O. Notably, almost all patients in Cohort A did not require any rescue opioid doses, resulting in a significantly reduced median rescue dose (6 versus 0 doses, p = 0.0017). Even when opioid doses were reduced due to PONV, Cohort A continued to exhibit significantly lower NRS scores. Conclusions Multimodal analgesia comprising the routine intravenous acetaminophen administration could be safe and effective after minimally invasive hepatectomy, without adverse effects regarding hepatic function. Acetaminophen Analgesics Opioid Postoperative Nausea and Vomiting Minimally invasive hepatectomy Figures Figure 1 Figure 2 Background Liver resection is technically challenging due to the liver’s complex anatomy and rich blood supply 1 . Effective post-operative pain management is essential for improving surgical outcomes 2 . Multimodal analgesia, including epidural anesthesia, intravenous opioids (such as fentanyl), peripheral nerve blocks (PNBs), non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen, is widely recognized for its effectiveness in managing postoperative pain following gastrointestinal surgery 3 , 4 . Epidural anesthesia is effective; however, it carries the risk of complications, such as hemorrhage and epidural hematoma, particularly in patients who develop post-hepatectomy coagulopathies 5 – 7 . Opioids are effective for pain relief; nonetheless, they are associated with an increased risk of adverse effects, including constipation, sedation, and postoperative nausea and vomiting (PONV) 8 , 9 . PONV negatively affects the postoperative quality of life and may delay mobilization, resulting in a prolonged hospital stay 10 . Despite concerns regarding hepatotoxicity, acetaminophen administration as postoperative analgesia following an open hepatectomy has been shown to be safe 11 , 12 . However, the safety and efficacy of acetaminophen administration post-minimally invasive hepatectomy (MIH) has not been fully established. Moreover, few studies have objectively assessed an improvement in postoperative pain management with acetaminophen administration 13 , 14 . We have hypothesized that the routine intravenous administration of acetaminophen provides effective postoperative analgesia, reduces the need for opioids, and minimizes the incidence of PONV in patients undergoing MIHs. Thus, in this study, we aimed to assess the safety and effectiveness of multimodal analgesia comprising the routine intravenous administration of acetaminophen in the postoperative pain management of MIH. Materials and Methods Ethical Considerations This study has been approved by the Ethics Committee (EC) of Yamaguchi University Hospital, with the EC approval number: 2024-020. Moreover, this study has been conducted in accordance with the principles of the World Medical Association Declaration of Helsinki involving human participants (as revised in Brazil 2013). Written informed consent was obtained from the participants for the collection of their samples and publication of their de-identified data and images. Participants and Methods In this retrospective single-center cohort study, 50 consecutive participants who had undergone MIHs between October 2021 and October 2022 were enrolled into the study; and their data were collected and analyzed. Anesthesia was managed with continuous intravenous remifentanil, fentanyl boluses, and sevoflurane inhalation. Nitrogen gas and epidural anesthesia were not administered. Some participants underwent peripheral nerve blocks (PNBs) during anesthetic management. All participants were managed with continuous intravenous fentanyl via intravenous patient-controlled postoperative analgesia. Dosages and rates had been calibrated by the anesthesiologist, according to the age and weight of each participant, with an initial rate of 0.3–0.5 µg/kg/h, bolus dose of 10–20 µg/dose, and total dose of 1000–2000 µg. The participants were divided into two cohorts: Cohort O (opioids-alone, without the routine administration of acetaminophen) and Cohort A (with the regular administration of acetaminophen). Regarding Cohort A, acetaminophen was administered every 6 h, until 48 h postoperatively, as per the manufacturer's protocol (body weight [BW] ≥ 50 kg: 1000 mg/dose; BW < 50 kg: 15 mg/kg/dose) (Fig. 1 ). Postoperative pain was evaluated for 2 days postoperatively, using a Numerical Rating Scale (NRS) at rest and during movement. The results were compared with the worst values of the day, evaluated at each visit. Furthermore, the total postoperative fentanyl dose and number of rescue doses were assessed. The frequency of PONV and sum of the antiemetic agent doses were evaluated for safety and adverse effects. Hepatic function was monitored using serum laboratory examinations on the first, third, fifth, and seventh postoperative days. Aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (T. Bil), and prothrombin time (PT) levels were measured to evaluate the potential hepatotoxic effects of acetaminophen. Statistical analyses The clinicopathological factors of Cohorts O and A were compared. Clinicopathological factors were analyzed using the Mann–Whitney U, Wilcoxon, and chi-square tests; while univariate survival analyses were performed using the Cox proportional hazards regression model. The cut-off value for the intraoperative fentanyl dose was determined using a receiver operating characteristic curve analysis. Participants who had undergone PNBs were further divided into sub-cohorts. Regarding these sub-cohort analyses, the NRS, total postoperative fentanyl doses, and number of rescue doses were compared between Cohorts O and A. Statistical analyses were performed using JMP 15 software (SAS Institute, Cary, NC, USA). Statistical significance was set at P < 0.05. Results Clinical and Surgical Factors This study included 50 participants who were divided into two cohorts: Cohort A (n = 25) and Cohort O (n = 25) (Table 1 ). Statistically significant differences were not observed between the two cohorts regarding the clinical features, including diseases and preoperative hepatic and renal functions. Ten and seven participants in Cohorts O and A, respectively, underwent hand-assisted laparoscopic surgeries, with no statistically significant differences noted in the types of laparotomies or liver resections. Table 1 Participants’ Demographic and Clinical Characteristics are Depicted O Cohort (n = 25) A Cohort (n = 25) P value Age 73.0 (55.1–94.0) 72.0 (48.5–83.1) 0.4669 Sex (Male) 19 (76.0) 19 (76.0) 1.0000 ASA–PS (1/2/3) 0/18 (72.0)/7(28.0) 1 (4.0)/21 (84.0)/3 (12.0) 0.2890 Height(cm) 161.1 (139.6–177.0) 162 (139.6 − 177.2) 0.9536 Weight (kg) 59.8 (42.0–91.0) 61.6 (43.0–87.2) 0.4787 BMI 22.9 (17.3–31.9) 23.3 (18.6–31.1) 0.3084 Diseases (HCC/ICC/metastasis/other) 13 (52.0)/3 (12.0)/9 (36.0)/0 11 (44.0)/1 (4.0)/11 (44.0)/2 (4.0) 0.4491 Type of liver resection (partial/≥ 1 section) 21 (84.0)/4 (16.0) 24 (96.0)/1 (4.0) 0.3487 Type of laparotomy (pure/HALS/robot) 15 (60.0)/10 (40.0)/0 16 (64.0)/7 (28.0)/2 (8.0) 0.3880 Tumor size (mm) 22 (10–190) 20 (10–40) 0.1462 Number of resected tumors 1 (1–12) 1 (1–3) 0.5087 Fibrosis (0/1/2/3/4/unexamined) 7/7/3/3/1/4 1/4/1/3/2/14 0.4186 Preoperative serum laboratory examination results Alb (g/dL) 4.0 (3.1–4.8) 4.1 (3.4–4.9) 0.1336 T.Bil (mg/dL) 0.7 (0.4–1.8) 0.6 (0.3–1.3) 0.1867 AST (IU/L) 27 (13–77) 22 (13–48) 0.0947 ALT (IU/L) 22 (9–81) 18 (8–70) 0.5797 Creatinine (mg/dL) 0.83 (0.54–1.29) 0.78 (0.48–1.77) 0.9073 eGFR (mL/min/1.73m 2 ) 66.0 (35.2–114.4) 66.5 (30.0–117.1) 0.8386 Platelets (x10 4 /uL) 18.5 (10.2–38.4) 17.7 (8.0–32.4) 0.9923 Prothrombin time (%) 98.8 (33.6–124.4) 97.2 (44.0–142.2) 0.7268 ICG-r15 (%) 11.7 (2.3–23.7) 9.1 (2.2–42.4) 0.1593 Operation time (min) 349 (216–735) 341 (143–639) 0.5869 Blood loss (g) 150 (4–880) 80 (1–630) 0.7268 Pringle maneuver (times) 5 (0–15) 5 (0–16) 0.5200 Median (range) n (%). Abbreviations: Alb = albumin; ALT = alanine transaminase; ASA–PS = American Society of Anesthesiologists–Physical Status; AST = aspartate transaminase; BMI = body mass index; eGFR = estimated glomerular filtration rate; ICG-r15 = indocyanine green retention test at 15 min; HALS = hand-assisted laparoscopic surgery; HCC = hepatocellular carcinoma; ICC = intrahepatic cholangiocarcinoma; T.Bil = total bilirubin. None of the participants in either cohort underwent conversion to open surgery. Short-term surgical outcomes, including operative time, blood loss, and severe morbidities (Clavien–Dindo grade ≥ IIIa) were statistically similar between cohorts. Cohort A had a statistically significantly shorter postoperative hospital stay than did Cohort O (median values: 9 and 11 days, respectively; P = 0.0228). Perioperative Serum Laboratory Examination Results and Routine Acetaminophen Administration To evaluate the safety of acetaminophen as postoperative analgesia for MIHs, perioperative serum laboratory examination results, reflective of and including hepatic and renal functions and systemic inflammation, were compared between the two cohorts. Perioperative liver function tests (AST, ALT, T. Bil, and PT) revealed an initial increase on the first postoperative day, followed by a gradual improvement over time (Fig. 2 ). No statistically significant differences in the liver function tests were observed between the two cohorts on the first, third, fifth, and seventh postoperative days (Fig. 2 a–d). Postoperative liver failure was not observed in any of the participants from either cohort. Additionally, renal function and systemic inflammatory markers were comparable between the two cohorts (Fig. 2 e, f). Postoperative Analgesia Assessment The efficacy of postoperative analgesia, comprising routine intravenous acetaminophen administration, was evaluated using the fentanyl doses, NRS scores, and incidence rates of PONV (Table 2 ). No statistically significant differences in the total fentanyl doses were observed between the two cohorts. However, the median number of rescue doses was statistically significantly higher in Cohort O (median value = 6 doses) than in Cohort A (median value = 0 doses) (P = 0.0017). Table 2 Fentanyl Dosage, Pain Scale, and Short-Term Outcomes Cohort O (n = 25) Cohort A (n = 25) P value Intraoperative dose of fentanyl (ug) 450 (250–800) 400 (150–1000) 0.7405 Postoperative dose of fentanyl (ug) 1500 (665–2000) 1500 (100–2000) 0.7770 Initial dosing rate of fentanyl(ug/h) 25.0 (12.5–45.0) 27.5 (12.5–42.5) 0.7106 Sum of rescue doses 6 (0–16) 0 (0–8) 0.0017 Reduction or discontinuation of fentanyl (+) 9 (36.0) 8 (32.0) 1.0000 Peripheral nerve block (+) 17 (68.0) 20 (80.0) 0.5202 POD1NRS at rest 4 (1–7) 2 (0–5) 0.0005 during movement 5 (1–10) 5 (1–10) 0.2319 POD2NRS at rest 2 (0–6) 2 (0–3) 0.1879 during movement 5 (0–10) 3 (1–8) 0.0195 PONV (+) 21 (84.0) 17 (68.0) 0.3209 Sum of anti-emetic agent doses 1 (0–9) 1 (0–5) 0.5781 Delirium 4 (16.0)/21 (84.0) 2 (8.0)/23 (92.0) 0.6671 Morbidity (C–D grade ≥ 3) 3 (12.0)/22 (88.0) 1 (4.0)/24 (96.0) 0.6092 Time-to-oral intake (days) 3 (2–11) 3 (2–3) 0.1497 Time-to-ambulation (days) 1 (1–1) 1 (1–1) 1.000 Length of postoperative hospital stay (days) 11 (8–19) 9 (7–114) 0.0228 Median (range) n (%). Abbreviations: C–D = Clavien–Dindo; NRS = numerical rating scale; POD = postoperative day; PONV = postoperative nausea and vomiting. The NRS scores at rest on the first postoperative day were statistically significantly lower in Cohort A (median score = 2) than in Cohort O (median score = 4) (P = 0.0005). Similarly, the NRS scores during movement on the second postoperative day were statistically significantly lower in Cohort A (median score = 3) than in Cohort O (median score = 5) (P = 0.0195). In Cohorts O and A respectively, 17 (68%) and 20 participants (80%) underwent PNBs, with no statistically significant differences observed. In a sub-cohort analysis of participants who underwent PNBs that might have affected postoperative pain, the median number of rescue doses was statistically significantly higher in Cohort O (median value: three doses) than in Cohort A (median value: one dose) (P = 0.0329). Moreover, the NRS scores at rest on the first postoperative day were statistically significantly higher in Cohort O (median score = 4) than in Cohort A (median score = 2) (P = 0.0004). Nine and eight participants in Cohorts O and A required fentanyl reduction or discontinuation due to PONV, respectively. No statistically significant differences in the PONV frequency, anti-emetic use, or fentanyl dose reduction were observed between the two cohorts. Assessment of Analgesia After Reduction or Discontinuation of Fentanyl The analgesic efficacy after the reduction or discontinuation of fentanyl was evaluated (Table 3 ). Of all the participants, some in Cohort O required frequent rescue doses of fentanyl. However, no statistically significant differences were observed between the two cohorts regarding the number of rescue doses required. Notably, the NRS scores during movement were statistically significantly lower in Cohort A (median score = 2) than in Cohort O (median score = 4) after fentanyl reduction (P = 0.0305). Participants in Cohort A did not report worsening of pain after fentanyl reduction; however, three participants in Cohort O reported increased pain during movement. Table 3 Postoperative Nausea and Vomiting and Pain Scale Post-Fentanyl Reduction Cohort O (n = 9) Cohort A (n = 8) P value Sum of rescue doses post-fentanyl reduction 0 (0–7) 0 (0–1) 0.2341 PONV(+) 6 (66.7) 3 (37.5) 0.3469 NRS at rest 2 (0–4) 1 (1–4) 0.2164 during movement 4 (2–8) 2 (1–4) 0.0305 Increase of NRS at rest 2 (22.2)/7 (77.8) 2 (25.0)/6 (75.0) 1.0000 during movement 3 (33.3)/6 (66.7) 0/8 (100.0) 0.2059 Median (range) n (%). Abbreviations: NRS = numerical rating scale; PONV = postoperative nausea and vomiting. Reduction of Total Fentanyl Dose and Risk Factors for PONV Table 4 presents the results of the univariate and multivariate analyses of PONV risk factors. The univariate analysis identified higher intraoperative fentanyl doses as a significant risk factor for PONV (P = 0.0257). However, the multivariate analysis did not identify any independent risk factors. Intraoperative factors, including increased blood loss, hand-assisted laparoscopic surgery, and larger tumor diameter, were correlated with a higher number of intraoperative fentanyl doses (Table 5 ). Table 4 Univariate and Multivariate Analyses of Risk Factors for Postoperative Nausea and Vomiting Univariate Multivariate OR 95% CI P-value OR 95% CI P-value Cohorts (O/A) 2.4706 0.6341–9.6253 0.1924 Sex (M/F) 0.5600 0.1043–3.0081 0.4990 Age 1.0223 0.9541–1.0954 0.5310 History of PONV/motion sickness - - - Smoking status (+/-) 0.2471 0.0476–1.2830 0.0962 0.3701 0.0647–2.1173 0.2640 Duration of anesthesia 0.9966 0.9915–1.0018 0.1977 Use of volatile anesthetics - - - Use of nitrous oxide - - - Intraoperative fentanyl doses 1.0042 1.0003–1.0081 0.0257 1.0034 0.9994–1.0074 0.0831 Postoperative fentanyl doses 0.9671 0.8859–1.0558 0.4346 Abbreviations: CI = confidence interval; OR = Odds ratio; PONV = postoperative nausea and vomiting. Table 5 Univariate and Multivariate Analyses of Risk Factors for Increased Intraoperative Fentanyl Doses Univariate Multivariate OR 95% CI P-value OR 95% CI P-value Cohorts (O/A) 0.8438 0.3778–3.7181 0.7709 Sex (M/F) 1.2245 0.3260–4.5996 0.7642 Age 0.9551 0.8944–1.1020 0.1549 Operation time (min) 1.0046 0.9994–1.0100 0.0648 Blood loss (g) 1.0045 1.0007–1.0082 0.0066 1.0026 0.9982–1.0070 0.2260 Type of laparotomy (HALS/other) 4.3922 1.0600–18.1999 0.0413 2.3106 0.3952–13.5079 0.3526 Tumor size (mm) 1.0440 0.9923–1.9835 0.0217 1.0336 0.9775–1.0930 0.1289 Number of resected tumors 2.1054 0.7051–6.2863 0.0553 Pringle maneuver (times) 0.9681 0.8371–1.1195 0.6621 Peripheral nerve block (+/-) 1.0268 02798–3.7674 0.9682 Abbreviations: CI = confidence interval; HALS = hand-assisted laparoscopic surgery; OR = odds ratio. Discussion Challenges involving perioperative pain management in liver resection, particularly regarding the administration of epidural anesthesia and opioids, still exist due to possible complications, such as hemorrhage and opioid-related adverse effects. The potential hepatotoxicity of acetaminophen has been a major concern in liver surgery 14 , 15 . Nonetheless, our study findings highlight the safety and efficacy thereof when used as part of a multimodal analgesia protocol for MIHs. First, the safety of acetaminophen was evaluated using perioperative serum laboratory examination results to confirm the presence or absence of liver failure (Fig. 2 ). Acetaminophen is commonly used as postoperative analgesia 4 . However, acetaminophen is metabolized in the liver and can potentially cause hepatotoxicity, causing liver surgeons to exercise caution regarding its administration 16 . Consequently, multimodal analgesia comprising the intravenous administration of acetaminophen could be a feasible approach. However, few studies exist regarding this administration as part of post-liver resection multimodal analgesia. Recently, the safety of acetaminophen for post-open hepatectomy analgesia has been revealed 14 , 15 . Hidaka et al. have assessed hepatic function using comprehensive measures, such as serum laboratory examinations and grading of fibrosis, confirming that acetaminophen does not exacerbate liver injury post-minimally invasive liver surgery 13 . Our findings are consistent with those of Hidaka et al., further supporting the hypothesis that acetaminophen can be safely administered to patients undergoing MIHs, particularly to those with potentially compromised hepatic function. Second, our study expanded on the work of Hidaka et al. by providing objective measures of postoperative pain management using the NRS, particularly revealing the reduced requirements for opioid rescue doses in patients receiving routine acetaminophen. This finding has been shown in other studies regarding gastrointestinal surgery 17 – 20 , but has not been thoroughly explored concerning MIHs. Thus, this study finding provides an important contribution to the understanding of the role of acetaminophen in postoperative pain management after MIHs. Third, we demonstrated that acetaminophen statistically significantly reduced the number of fentanyl rescue doses required during the early postoperative phase, particularly during movement, which is commonly the most challenging period for pain management. Thus, these findings revealed that regular acetaminophen intravenous administration may facilitate early mobilization and reduce postoperative hospital stays, aligning with the results of previous studies regarding other gastrointestinal surgeries 20 – 22 . These results indicate that routine intravenous administration of acetaminophen may be effective for post-MIH analgesia. Furthermore, in recent years, as the usefulness of MIHs has been established and their development and adoption are expected to increase, the reduction in postoperative hospital stays may contribute to a more efficient use of medical resources and potential decrease in healthcare costs 23 , 24 . Acetaminophen effectively reduced the need for opioid rescue doses; however, its impact regarding lesser opioid-related adverse effects, such as PONV, was not as pronounced as in studies involving other gastrointestinal surgeries 25 . A possible explanation for this is that the total fentanyl dose, rather than the number of rescue doses, plays a more clinically significant role in the development of PONV. Analgesia and nausea are controlled by distinct physiological mechanisms and high plasma concentrations of fentanyl-stimulated µ-opioid receptors in the medulla and chemoreceptor trigger zone (CTZ), triggering nausea 25 , 26 . In our study, acetaminophen appeared to reduce the requirement for rescue fentanyl doses; however, the total intraoperative and postoperative opioid doses were comparable between the cohorts, which may explain why we did not observe a statistically significant reduction in PONV. Further analysis revealed that the total intraoperative opioid dose was a statistically significant contributor to the development of PONV. Intraoperative opioid administration typically involves rapid bolus dosing, which can result in sharp increases in plasma opioid concentrations, overstimulation of medullary CTZ, and the induction of nausea and vomiting 27 . Based on these findings, we are planning a prospective clinical trial to determine whether greater reductions in the total opioid dose, achieved through alternative analgesic strategies or higher doses of acetaminophen, could result in more pronounced reductions in PONV, thus maintaining pain management for MIH. Our sub-cohort analysis revealed that, particularly among patients receiving PNBs, those administered routine acetaminophen had lower pain scores, showing that acetaminophen may enhance pain management beyond the effects of PNBs alone, which are known for their strong analgesic effect during the early postoperative period of abdominal surgery 28 . Studies have indicated that acetaminophen acts peripherally by inhibiting cyclooxygenase enzymes and centrally by engaging the serotonergic pathways 29 , 30 . Therefore, combined with the local action of PNBs, acetaminophen may provide more comprehensive pain management. Study limitations include the single-center, small-sample design; in addition to the potential biases inherent to the retrospective nature of the study. Future research should comprise multicenter, prospective studies with larger cohorts to validate these findings and further explore the optimal dosing and timing of acetaminophen administration regarding multimodal analgesia for MIHs. Finally, the study predominantly consisted of participants who had undergone partial hepatectomies. Therefore, the safety of acetaminophen during major liver resections using minimally invasive techniques, requires further investigation. Conclusions In conclusion, multimodal analgesia comprising the routine intravenous administration of acetaminophen could be effective and safe post-MIHs, without adverse effects regarding hepatic function. Declarations Ethics approval and consent to participate This study has been approved by the Ethics Committee (EC) of Yamaguchi University Hospital, with the EC approval number: 2024-020. Moreover, this study has been conducted in accordance with the principles of the World Medical Association Declaration of Helsinki involving human participants (as revised in Brazil 2013). Patient Consent Statement Written informed consent was obtained from the participants for the collection of their samples and publication of their de-identified data and images. Consent for publication Consent to Publish declaration: not applicable Availability of data and materials Data available on request from the authors: The data that support the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Conflict of Interest Disclosure Authors declare no Conflict of Interests for this article. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions KF, MN and YT designed this study. KF, MN, YT, YS, HM, YK, YN, YW, ST, NM, MI, HT, TI, TU and HN collected and analyzed the data for the study. KF and MN prepared the manuscript. HN supervised the study. All authors are in agreement with the contents of the manuscript. 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Postoperative scheduled intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy in Japan. Mathews J Anesth. 2018;34:502–11. Ohkura Y, Haruta S, Shindoh J, Tanaka T, Ueno M, Udagawa H. Effectiveness of postoperative intravenous acetaminophen (Acelio) after gastrectomy: A propensity score-matched analysis. Med (Baltim). 2016;95:e5352. Ohkura Y, Shindoh J, Ueno M, Iizuka T, Haruta S, Udagawa H. A new postoperative pain management (intravenous acetaminophen: Acelio®) leads to enhanced recovery after esophagectomy: a propensity score-matched analysis. Surg Today. 2018;48:502–9. Adachi T, Hara T, Matsushima H, Soyama A, Eguchi S. Essential updates 2022/2023: A review of current topics in robotic hepatectomy. Ann Gastroenterol Surg. 2024;8:774–7. Cassese G, Han HS, Lee E, Lee B, Lee HW, Cho JY, Montalti R, Troisi RI. Laparoscopic versus open liver resection for multiple hepatocellular carcinoma within and beyond the Milan criteria: An Eastern-Western propensity score-matched analysis. J Hepatobiliary Pancreat Sci. 2024;31:2–11. O'Neill A, Lirk P. Multimodal analgesia. Anesthesiol Clin. 2022;40:455–68. Chandrakantan A, Glass PS. Multimodal therapies for postoperative nausea and vomiting, and pain. Br J Anaesth. 2011;107(Suppl 1):i27–40. Apfel CC, Heidrich FM, Jukar-Rao S, Jalota L, Hornuss C, Whelan RP, Zhang K, Cakmakkaya OS. Evidence-based analysis of risk factors for postoperative nausea and vomiting. Br J Anaesth. 2012;109:742–53. Kıtlık A, Erdogan MA, Ozgul U, Aydogan MS, Ucar M, Toprak HI, Colak C, Durmus M. Ultrasound-guided transversus abdominis plane block for postoperative analgesia in living liver donors: A prospective, randomized, double-blinded clinical trial. J Clin Anesth. 2017;37:103–7. Botting RM. Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clin Infect Dis. 2000;31(Suppl 5):S202–210. Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006;79:371–8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Surgery → Version 1 posted Editorial decision: Revision requested 11 Jul, 2025 Reviews received at journal 07 Jul, 2025 Reviews received at journal 02 Jul, 2025 Reviewers agreed at journal 25 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviews received at journal 09 Jun, 2025 Reviewers agreed at journal 31 May, 2025 Reviewers invited by journal 28 May, 2025 Editor invited by journal 06 May, 2025 Editor assigned by journal 06 May, 2025 Submission checks completed at journal 06 May, 2025 First submitted to journal 26 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6533986","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":463202664,"identity":"660e3633-497c-4e85-8fe9-747bb41f8bd0","order_by":0,"name":"Kei Furuya","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kei","middleName":"","lastName":"Furuya","suffix":""},{"id":463202665,"identity":"9d24573d-b1e8-409a-b7fd-b7e5ee0da391","order_by":1,"name":"Masao Nakajima","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masao","middleName":"","lastName":"Nakajima","suffix":""},{"id":463202666,"identity":"1524e896-21aa-4619-bc29-d12903bf5774","order_by":2,"name":"Yukio Tokumitsu","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yukio","middleName":"","lastName":"Tokumitsu","suffix":""},{"id":463202668,"identity":"09e3dd9f-0e52-45c5-827f-47e7e3805292","order_by":3,"name":"Yoshitaro Shindo","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yoshitaro","middleName":"","lastName":"Shindo","suffix":""},{"id":463202669,"identity":"b6af75c8-8f61-47ab-872f-a8d80b30b2ba","order_by":4,"name":"Hiroto Matsui","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hiroto","middleName":"","lastName":"Matsui","suffix":""},{"id":463202670,"identity":"f63ef6fb-66b5-4b18-aceb-5d8bb02ebe73","order_by":5,"name":"Yuta Kimura","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuta","middleName":"","lastName":"Kimura","suffix":""},{"id":463202671,"identity":"76b18e1a-1421-4819-84bd-23025e3ac742","order_by":6,"name":"Yuki Nakagami","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Nakagami","suffix":""},{"id":463202672,"identity":"d2da3ccf-40d1-4ea6-ad3c-26a51ac1b5ac","order_by":7,"name":"Yusaku Watanabe","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yusaku","middleName":"","lastName":"Watanabe","suffix":""},{"id":463202673,"identity":"b2e7429e-ee04-4d98-bb54-d2b5835cf381","order_by":8,"name":"Shinobu Tomochika","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shinobu","middleName":"","lastName":"Tomochika","suffix":""},{"id":463202674,"identity":"2d138763-2410-43bf-9c38-c62b425a37ad","order_by":9,"name":"Noriko Maeda","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Noriko","middleName":"","lastName":"Maeda","suffix":""},{"id":463202675,"identity":"72f2257b-c628-48ff-a7db-38260dc1536a","order_by":10,"name":"Michihisa Iida","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Michihisa","middleName":"","lastName":"Iida","suffix":""},{"id":463202676,"identity":"f8d57ee7-71d2-411a-9c3c-9f393b4fa56a","order_by":11,"name":"Hidenori Takahashi","email":"","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hidenori","middleName":"","lastName":"Takahashi","suffix":""},{"id":463202677,"identity":"8c2c065c-2a50-4d15-8872-5124587dd52b","order_by":12,"name":"Tatsuya Ioka","email":"","orcid":"","institution":"Yamaguchi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tatsuya","middleName":"","lastName":"Ioka","suffix":""},{"id":463202678,"identity":"d7ecbbdd-5c00-476d-bd33-e7e3c77198c9","order_by":13,"name":"Tomio Ueno","email":"","orcid":"","institution":"Kawasaki Medical School","correspondingAuthor":false,"prefix":"","firstName":"Tomio","middleName":"","lastName":"Ueno","suffix":""},{"id":463202679,"identity":"51e4926b-4974-4aca-82df-e7f898ccdb30","order_by":14,"name":"Hiroaki Nagano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYBACAygtBxNIYIMymAlpMSZdS2IDTAtBh5lLNz9+8XOHTfqG46cTP35ts8vjY+AxYPhRw8BujkOL5ZxjZpa9Z9JyN5zJ3Swt25ZczAbUwthzjIHZsgG7FoMbCWYGvG2HczccyN0gLdl2ILFN/o0BA28DA7PBAVxa0r8Z/m07nG5w/u3m32AtIFv+4tWSY/wYaEuCwY3cbZIfoVqY8duSU8Ys25ZmOPPG223WDOeSgVrYCg7LHJPA45f0zR/fttnI853P3XzzR5ld4vwG5o0P39TYJOMKMSBgkwCRCkBnMPNAhYBsiWQDnDoYmD+ASHmgMxh/IAnb4dEyCkbBKBgFIwsAACiyXmb8JWjAAAAAAElFTkSuQmCC","orcid":"","institution":"Yamaguchi University Graduate School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Hiroaki","middleName":"","lastName":"Nagano","suffix":""}],"badges":[],"createdAt":"2025-04-26 09:23:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6533986/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6533986/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12893-025-03169-0","type":"published","date":"2025-10-03T15:57:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83813303,"identity":"fb5257d7-50ef-4d50-97f8-ffe3c87b7b11","added_by":"auto","created_at":"2025-06-03 07:21:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":7257614,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy design is depicted\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData of the study participants from the period of October 2021 to October 2022 have been included. The participants have been either assigned to the opioid-alone cohort (Cohort O, n = 25) or opioid with routine intravenous acetaminophen administration cohort (Cohort A, n = 25) for postoperative analgesia. Both cohorts have received continuous intravenous fentanyl. Cohort A has received intravenous acetaminophen every 6 h, until 48 h postoperatively, according to the manufacturer's protocol. Abbreviation: BW, body weight\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6533986/v1/4a1aa44c3593a4c7b326178e.png"},{"id":83812632,"identity":"8a54adcf-0840-4b0d-ad04-bb0719c4822a","added_by":"auto","created_at":"2025-06-03 07:13:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2562371,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePerioperative serum laboratory examination trends are shown\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHepatic and renal functions and systemic inflammation have been evaluated using serum laboratory examination results on preoperative and the first, third, fifth, and seventh postoperative days. In (a)–(d), abnormal values are observed in the early postoperative period; however, these have quickly improved and do not differ between the two cohorts. Furthermore, renal function and systemic inflammation do not differ between the two cohorts.\u003c/p\u003e\n\u003cp\u003eAbbreviations: (a) AST, aspartate transaminase; (b) ALT, alanine transaminase; (c) T. Bil, total bilirubin; (d) PT, prothrombin time; (e) Cre, creatinine; (f) CRP, C-reactive protein; (g) POD, postoperative day.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6533986/v1/63ee7c2df2e3233707942aa4.png"},{"id":92883725,"identity":"1fab80dd-e5a0-4fa6-9389-f48c695ba338","added_by":"auto","created_at":"2025-10-06 16:08:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13946933,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6533986/v1/e6629916-4961-4ad6-a1c7-bec79f297a94.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Routine Use of Intravenous Acetaminophen Safely Enhances Pain Control After Minimally Invasive Hepatectomies: a retrospective cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eLiver resection is technically challenging due to the liver\u0026rsquo;s complex anatomy and rich blood supply\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Effective post-operative pain management is essential for improving surgical outcomes\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Multimodal analgesia, including epidural anesthesia, intravenous opioids (such as fentanyl), peripheral nerve blocks (PNBs), non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen, is widely recognized for its effectiveness in managing postoperative pain following gastrointestinal surgery\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEpidural anesthesia is effective; however, it carries the risk of complications, such as hemorrhage and epidural hematoma, particularly in patients who develop post-hepatectomy coagulopathies\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Opioids are effective for pain relief; nonetheless, they are associated with an increased risk of adverse effects, including constipation, sedation, and postoperative nausea and vomiting (PONV)\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. PONV negatively affects the postoperative quality of life and may delay mobilization, resulting in a prolonged hospital stay\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite concerns regarding hepatotoxicity, acetaminophen administration as postoperative analgesia following an open hepatectomy has been shown to be safe\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. However, the safety and efficacy of acetaminophen administration post-minimally invasive hepatectomy (MIH) has not been fully established. Moreover, few studies have objectively assessed an improvement in postoperative pain management with acetaminophen administration\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. We have hypothesized that the routine intravenous administration of acetaminophen provides effective postoperative analgesia, reduces the need for opioids, and minimizes the incidence of PONV in patients undergoing MIHs. Thus, in this study, we aimed to assess the safety and effectiveness of multimodal analgesia comprising the routine intravenous administration of acetaminophen in the postoperative pain management of MIH.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthical Considerations\u003c/h2\u003e \u003cp\u003e This study has been approved by the Ethics Committee (EC) of Yamaguchi University Hospital, with the EC approval number: 2024-020. Moreover, this study has been conducted in accordance with the principles of the World Medical Association Declaration of Helsinki involving human participants (as revised in Brazil 2013). Written informed consent was obtained from the participants for the collection of their samples and publication of their de-identified data and images.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants and Methods\u003c/h3\u003e\n\u003cp\u003eIn this retrospective single-center cohort study, 50 consecutive participants who had undergone MIHs between October 2021 and October 2022 were enrolled into the study; and their data were collected and analyzed. Anesthesia was managed with continuous intravenous remifentanil, fentanyl boluses, and sevoflurane inhalation. Nitrogen gas and epidural anesthesia were not administered. Some participants underwent peripheral nerve blocks (PNBs) during anesthetic management. All participants were managed with continuous intravenous fentanyl via intravenous patient-controlled postoperative analgesia. Dosages and rates had been calibrated by the anesthesiologist, according to the age and weight of each participant, with an initial rate of 0.3\u0026ndash;0.5 \u0026micro;g/kg/h, bolus dose of 10\u0026ndash;20 \u0026micro;g/dose, and total dose of 1000\u0026ndash;2000 \u0026micro;g.\u003c/p\u003e \u003cp\u003eThe participants were divided into two cohorts: Cohort O (opioids-alone, without the routine administration of acetaminophen) and Cohort A (with the regular administration of acetaminophen). Regarding Cohort A, acetaminophen was administered every 6 h, until 48 h postoperatively, as per the manufacturer's protocol (body weight [BW]\u0026thinsp;\u0026ge;\u0026thinsp;50 kg: 1000 mg/dose; BW\u0026thinsp;\u0026lt;\u0026thinsp;50 kg: 15 mg/kg/dose) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePostoperative pain was evaluated for 2 days postoperatively, using a Numerical Rating Scale (NRS) at rest and during movement. The results were compared with the worst values of the day, evaluated at each visit. Furthermore, the total postoperative fentanyl dose and number of rescue doses were assessed. The frequency of PONV and sum of the antiemetic agent doses were evaluated for safety and adverse effects. Hepatic function was monitored using serum laboratory examinations on the first, third, fifth, and seventh postoperative days. Aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (T. Bil), and prothrombin time (PT) levels were measured to evaluate the potential hepatotoxic effects of acetaminophen.\u003c/p\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eThe clinicopathological factors of Cohorts O and A were compared. Clinicopathological factors were analyzed using the Mann\u0026ndash;Whitney U, Wilcoxon, and chi-square tests; while univariate survival analyses were performed using the Cox proportional hazards regression model. The cut-off value for the intraoperative fentanyl dose was determined using a receiver operating characteristic curve analysis. Participants who had undergone PNBs were further divided into sub-cohorts. Regarding these sub-cohort analyses, the NRS, total postoperative fentanyl doses, and number of rescue doses were compared between Cohorts O and A. Statistical analyses were performed using JMP 15 software (SAS Institute, Cary, NC, USA). Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Surgical Factors\u003c/h2\u003e \u003cp\u003eThis study included 50 participants who were divided into two cohorts: Cohort A (n\u0026thinsp;=\u0026thinsp;25) and Cohort O (n\u0026thinsp;=\u0026thinsp;25) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Statistically significant differences were not observed between the two cohorts regarding the clinical features, including diseases and preoperative hepatic and renal functions. Ten and seven participants in Cohorts O and A, respectively, underwent hand-assisted laparoscopic surgeries, with no statistically significant differences noted in the types of laparotomies or liver resections.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParticipants\u0026rsquo; Demographic and Clinical Characteristics are Depicted\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eO Cohort\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA Cohort\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.0 (55.1\u0026ndash;94.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.0 (48.5\u0026ndash;83.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4669\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (76.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (76.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA\u0026ndash;PS (1/2/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/18 (72.0)/7(28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0)/21 (84.0)/3 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2890\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight(cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e161.1 (139.6\u0026ndash;177.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162 (139.6 \u0026minus;\u0026thinsp;177.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9536\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.8 (42.0\u0026ndash;91.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.6 (43.0\u0026ndash;87.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4787\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.9 (17.3\u0026ndash;31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.3 (18.6\u0026ndash;31.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3084\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiseases (HCC/ICC/metastasis/other)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (52.0)/3 (12.0)/9 (36.0)/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (44.0)/1 (4.0)/11 (44.0)/2 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4491\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of liver resection (partial/\u0026ge; 1 section)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (84.0)/4 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (96.0)/1 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3487\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of laparotomy (pure/HALS/robot)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (60.0)/10 (40.0)/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (64.0)/7 (28.0)/2 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3880\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (10\u0026ndash;190)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (10\u0026ndash;40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1462\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of resected tumors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrosis (0/1/2/3/4/unexamined)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/7/3/3/1/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/4/1/3/2/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4186\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative serum laboratory examination results\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlb (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.0 (3.1\u0026ndash;4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.1 (3.4\u0026ndash;4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1336\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT.Bil (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7 (0.4\u0026ndash;1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6 (0.3\u0026ndash;1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1867\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (13\u0026ndash;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (13\u0026ndash;48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0947\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (9\u0026ndash;81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (8\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5797\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.83 (0.54\u0026ndash;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78 (0.48\u0026ndash;1.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9073\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR (mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.0 (35.2\u0026ndash;114.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.5 (30.0\u0026ndash;117.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.8386\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (x10\u003csup\u003e4\u003c/sup\u003e/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.5 (10.2\u0026ndash;38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.7 (8.0\u0026ndash;32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9923\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProthrombin time (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.8 (33.6\u0026ndash;124.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.2 (44.0\u0026ndash;142.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7268\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICG-r15 (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.7 (2.3\u0026ndash;23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.1 (2.2\u0026ndash;42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperation time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e349 (216\u0026ndash;735)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e341 (143\u0026ndash;639)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5869\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (4\u0026ndash;880)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (1\u0026ndash;630)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7268\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePringle maneuver (times)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (0\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (0\u0026ndash;16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eMedian (range) n (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: Alb\u0026thinsp;=\u0026thinsp;albumin; ALT\u0026thinsp;=\u0026thinsp;alanine transaminase; ASA\u0026ndash;PS\u0026thinsp;=\u0026thinsp;American Society of Anesthesiologists\u0026ndash;Physical Status; AST\u0026thinsp;=\u0026thinsp;aspartate transaminase; BMI\u0026thinsp;=\u0026thinsp;body mass index; eGFR\u0026thinsp;=\u0026thinsp;estimated glomerular filtration rate; ICG-r15\u0026thinsp;=\u0026thinsp;indocyanine green retention test at 15 min; HALS\u0026thinsp;=\u0026thinsp;hand-assisted laparoscopic surgery; HCC\u0026thinsp;=\u0026thinsp;hepatocellular carcinoma; ICC\u0026thinsp;=\u0026thinsp;intrahepatic cholangiocarcinoma; T.Bil\u0026thinsp;=\u0026thinsp;total bilirubin.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNone of the participants in either cohort underwent conversion to open surgery. Short-term surgical outcomes, including operative time, blood loss, and severe morbidities (Clavien\u0026ndash;Dindo grade\u0026thinsp;\u0026ge;\u0026thinsp;IIIa) were statistically similar between cohorts. Cohort A had a statistically significantly shorter postoperative hospital stay than did Cohort O (median values: 9 and 11 days, respectively; P\u0026thinsp;=\u0026thinsp;0.0228).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePerioperative Serum Laboratory Examination Results and Routine Acetaminophen Administration\u003c/h2\u003e \u003cp\u003eTo evaluate the safety of acetaminophen as postoperative analgesia for MIHs, perioperative serum laboratory examination results, reflective of and including hepatic and renal functions and systemic inflammation, were compared between the two cohorts. Perioperative liver function tests (AST, ALT, T. Bil, and PT) revealed an initial increase on the first postoperative day, followed by a gradual improvement over time (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No statistically significant differences in the liver function tests were observed between the two cohorts on the first, third, fifth, and seventh postoperative days (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea\u0026ndash;d). Postoperative liver failure was not observed in any of the participants from either cohort. Additionally, renal function and systemic inflammatory markers were comparable between the two cohorts (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee, f).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePostoperative Analgesia Assessment\u003c/h3\u003e\n\u003cp\u003eThe efficacy of postoperative analgesia, comprising routine intravenous acetaminophen administration, was evaluated using the fentanyl doses, NRS scores, and incidence rates of PONV (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No statistically significant differences in the total fentanyl doses were observed between the two cohorts. However, the median number of rescue doses was statistically significantly higher in Cohort O (median value\u0026thinsp;=\u0026thinsp;6 doses) than in Cohort A (median value\u0026thinsp;=\u0026thinsp;0 doses) (P\u0026thinsp;=\u0026thinsp;0.0017).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFentanyl Dosage, Pain Scale, and Short-Term Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCohort O\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCohort A\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative dose of fentanyl (ug)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e450 (250\u0026ndash;800)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e400 (150\u0026ndash;1000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7405\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative dose of fentanyl (ug)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1500 (665\u0026ndash;2000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1500 (100\u0026ndash;2000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7770\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial dosing rate of fentanyl(ug/h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.0 (12.5\u0026ndash;45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.5 (12.5\u0026ndash;42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSum of rescue doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (0\u0026ndash;16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReduction or discontinuation of fentanyl (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (36.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral nerve block (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (68.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5202\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD1NRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eat rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1\u0026ndash;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eduring movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2319\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD2NRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eat rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1879\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eduring movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (0\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePONV (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (84.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (68.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSum of anti-emetic agent doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0\u0026ndash;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5781\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelirium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (16.0)/21 (84.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.0)/23 (92.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6671\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorbidity (C\u0026ndash;D grade\u0026thinsp;\u0026ge;\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12.0)/22 (88.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0)/24 (96.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime-to-oral intake (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1497\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime-to-ambulation (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of postoperative hospital stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (8\u0026ndash;19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (7\u0026ndash;114)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eMedian (range) n (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: C\u0026ndash;D\u0026thinsp;=\u0026thinsp;Clavien\u0026ndash;Dindo; NRS\u0026thinsp;=\u0026thinsp;numerical rating scale; POD\u0026thinsp;=\u0026thinsp;postoperative day; PONV\u0026thinsp;=\u0026thinsp;postoperative nausea and vomiting.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe NRS scores at rest on the first postoperative day were statistically significantly lower in Cohort A (median score\u0026thinsp;=\u0026thinsp;2) than in Cohort O (median score\u0026thinsp;=\u0026thinsp;4) (P\u0026thinsp;=\u0026thinsp;0.0005). Similarly, the NRS scores during movement on the second postoperative day were statistically significantly lower in Cohort A (median score\u0026thinsp;=\u0026thinsp;3) than in Cohort O (median score\u0026thinsp;=\u0026thinsp;5) (P\u0026thinsp;=\u0026thinsp;0.0195). In Cohorts O and A respectively, 17 (68%) and 20 participants (80%) underwent PNBs, with no statistically significant differences observed.\u003c/p\u003e \u003cp\u003eIn a sub-cohort analysis of participants who underwent PNBs that might have affected postoperative pain, the median number of rescue doses was statistically significantly higher in Cohort O (median value: three doses) than in Cohort A (median value: one dose) (P\u0026thinsp;=\u0026thinsp;0.0329). Moreover, the NRS scores at rest on the first postoperative day were statistically significantly higher in Cohort O (median score\u0026thinsp;=\u0026thinsp;4) than in Cohort A (median score\u0026thinsp;=\u0026thinsp;2) (P\u0026thinsp;=\u0026thinsp;0.0004).\u003c/p\u003e \u003cp\u003eNine and eight participants in Cohorts O and A required fentanyl reduction or discontinuation due to PONV, respectively. No statistically significant differences in the PONV frequency, anti-emetic use, or fentanyl dose reduction were observed between the two cohorts.\u003c/p\u003e\n\u003ch3\u003eAssessment of Analgesia After Reduction or Discontinuation of Fentanyl\u003c/h3\u003e\n\u003cp\u003eThe analgesic efficacy after the reduction or discontinuation of fentanyl was evaluated (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Of all the participants, some in Cohort O required frequent rescue doses of fentanyl. However, no statistically significant differences were observed between the two cohorts regarding the number of rescue doses required. Notably, the NRS scores during movement were statistically significantly lower in Cohort A (median score\u0026thinsp;=\u0026thinsp;2) than in Cohort O (median score\u0026thinsp;=\u0026thinsp;4) after fentanyl reduction (P\u0026thinsp;=\u0026thinsp;0.0305). Participants in Cohort A did not report worsening of pain after fentanyl reduction; however, three participants in Cohort O reported increased pain during movement.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostoperative Nausea and Vomiting and Pain Scale Post-Fentanyl Reduction\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCohort O\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCohort A\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSum of rescue doses post-fentanyl reduction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2341\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePONV(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3469\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eat rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2164\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eduring movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0305\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncrease of NRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eat rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (22.2)/7 (77.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (25.0)/6 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eduring movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (33.3)/6 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/8 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eMedian (range) n (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: NRS\u0026thinsp;=\u0026thinsp;numerical rating scale; PONV\u0026thinsp;=\u0026thinsp;postoperative nausea and vomiting.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eReduction of Total Fentanyl Dose and Risk Factors for PONV\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents the results of the univariate and multivariate analyses of PONV risk factors. The univariate analysis identified higher intraoperative fentanyl doses as a significant risk factor for PONV (P\u0026thinsp;=\u0026thinsp;0.0257). However, the multivariate analysis did not identify any independent risk factors. Intraoperative factors, including increased blood loss, hand-assisted laparoscopic surgery, and larger tumor diameter, were correlated with a higher number of intraoperative fentanyl doses (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and Multivariate Analyses of Risk Factors for Postoperative Nausea and Vomiting\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCohorts (O/A)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.4706\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6341\u0026ndash;9.6253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1924\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1043\u0026ndash;3.0081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9541\u0026ndash;1.0954\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of PONV/motion sickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking status (+/-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2471\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0476\u0026ndash;1.2830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0962\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0647\u0026ndash;2.1173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2640\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of anesthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9966\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9915\u0026ndash;1.0018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1977\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of volatile anesthetics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of nitrous oxide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative fentanyl doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0003\u0026ndash;1.0081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9994\u0026ndash;1.0074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0831\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative fentanyl doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9671\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8859\u0026ndash;1.0558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: CI\u0026thinsp;=\u0026thinsp;confidence interval; OR\u0026thinsp;=\u0026thinsp;Odds ratio; PONV\u0026thinsp;=\u0026thinsp;postoperative nausea and vomiting.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and Multivariate Analyses of Risk Factors for Increased Intraoperative Fentanyl Doses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCohorts (O/A)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3778\u0026ndash;3.7181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7709\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3260\u0026ndash;4.5996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8944\u0026ndash;1.1020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1549\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperation time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9994\u0026ndash;1.0100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0007\u0026ndash;1.0082\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9982\u0026ndash;1.0070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of laparotomy (HALS/other)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3922\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0600\u0026ndash;18.1999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.3106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.3952\u0026ndash;13.5079\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3526\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9923\u0026ndash;1.9835\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9775\u0026ndash;1.0930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of resected tumors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7051\u0026ndash;6.2863\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0553\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePringle maneuver (times)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9681\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8371\u0026ndash;1.1195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral nerve block (+/-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e02798\u0026ndash;3.7674\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9682\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: CI\u0026thinsp;=\u0026thinsp;confidence interval; HALS\u0026thinsp;=\u0026thinsp;hand-assisted laparoscopic surgery; OR\u0026thinsp;=\u0026thinsp;odds ratio.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eChallenges involving perioperative pain management in liver resection, particularly regarding the administration of epidural anesthesia and opioids, still exist due to possible complications, such as hemorrhage and opioid-related adverse effects. The potential hepatotoxicity of acetaminophen has been a major concern in liver surgery\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Nonetheless, our study findings highlight the safety and efficacy thereof when used as part of a multimodal analgesia protocol for MIHs.\u003c/p\u003e\n\u003cp\u003eFirst, the safety of acetaminophen was evaluated using perioperative serum laboratory examination results to confirm the presence or absence of liver failure (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Acetaminophen is commonly used as postoperative analgesia\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. However, acetaminophen is metabolized in the liver and can potentially cause hepatotoxicity, causing liver surgeons to exercise caution regarding its administration\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Consequently, multimodal analgesia comprising the intravenous administration of acetaminophen could be a feasible approach. However, few studies exist regarding this administration as part of post-liver resection multimodal analgesia. Recently, the safety of acetaminophen for post-open hepatectomy analgesia has been revealed\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Hidaka et al. have assessed hepatic function using comprehensive measures, such as serum laboratory examinations and grading of fibrosis, confirming that acetaminophen does not exacerbate liver injury post-minimally invasive liver surgery\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Our findings are consistent with those of Hidaka et al., further supporting the hypothesis that acetaminophen can be safely administered to patients undergoing MIHs, particularly to those with potentially compromised hepatic function.\u003c/p\u003e\n\u003cp\u003eSecond, our study expanded on the work of Hidaka et al. by providing objective measures of postoperative pain management using the NRS, particularly revealing the reduced requirements for opioid rescue doses in patients receiving routine acetaminophen. This finding has been shown in other studies regarding gastrointestinal surgery\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e, but has not been thoroughly explored concerning MIHs. Thus, this study finding provides an important contribution to the understanding of the role of acetaminophen in postoperative pain management after MIHs.\u003c/p\u003e\n\u003cp\u003eThird, we demonstrated that acetaminophen statistically significantly reduced the number of fentanyl rescue doses required during the early postoperative phase, particularly during movement, which is commonly the most challenging period for pain management. Thus, these findings revealed that regular acetaminophen intravenous administration may facilitate early mobilization and reduce postoperative hospital stays, aligning with the results of previous studies regarding other gastrointestinal surgeries\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. These results indicate that routine intravenous administration of acetaminophen may be effective for post-MIH analgesia. Furthermore, in recent years, as the usefulness of MIHs has been established and their development and adoption are expected to increase, the reduction in postoperative hospital stays may contribute to a more efficient use of medical resources and potential decrease in healthcare costs\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAcetaminophen effectively reduced the need for opioid rescue doses; however, its impact regarding lesser opioid-related adverse effects, such as PONV, was not as pronounced as in studies involving other gastrointestinal surgeries\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. A possible explanation for this is that the total fentanyl dose, rather than the number of rescue doses, plays a more clinically significant role in the development of PONV. Analgesia and nausea are controlled by distinct physiological mechanisms and high plasma concentrations of fentanyl-stimulated µ-opioid receptors in the medulla and chemoreceptor trigger zone (CTZ), triggering nausea\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. In our study, acetaminophen appeared to reduce the requirement for rescue fentanyl doses; however, the total intraoperative and postoperative opioid doses were comparable between the cohorts, which may explain why we did not observe a statistically significant reduction in PONV. Further analysis revealed that the total intraoperative opioid dose was a statistically significant contributor to the development of PONV. Intraoperative opioid administration typically involves rapid bolus dosing, which can result in sharp increases in plasma opioid concentrations, overstimulation of medullary CTZ, and the induction of nausea and vomiting\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Based on these findings, we are planning a prospective clinical trial to determine whether greater reductions in the total opioid dose, achieved through alternative analgesic strategies or higher doses of acetaminophen, could result in more pronounced reductions in PONV, thus maintaining pain management for MIH.\u003c/p\u003e\n\u003cp\u003eOur sub-cohort analysis revealed that, particularly among patients receiving PNBs, those administered routine acetaminophen had lower pain scores, showing that acetaminophen may enhance pain management beyond the effects of PNBs alone, which are known for their strong analgesic effect during the early postoperative period of abdominal surgery\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Studies have indicated that acetaminophen acts peripherally by inhibiting cyclooxygenase enzymes and centrally by engaging the serotonergic pathways\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Therefore, combined with the local action of PNBs, acetaminophen may provide more comprehensive pain management.\u003c/p\u003e\n\u003cp\u003eStudy limitations include the single-center, small-sample design; in addition to the potential biases inherent to the retrospective nature of the study. Future research should comprise multicenter, prospective studies with larger cohorts to validate these findings and further explore the optimal dosing and timing of acetaminophen administration regarding multimodal analgesia for MIHs. Finally, the study predominantly consisted of participants who had undergone partial hepatectomies. Therefore, the safety of acetaminophen during major liver resections using minimally invasive techniques, requires further investigation.\u003c/p\u003e\n\n"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, multimodal analgesia comprising the routine intravenous administration of acetaminophen could be effective and safe post-MIHs, without adverse effects regarding hepatic function.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has been approved by the Ethics Committee (EC) of Yamaguchi University Hospital, with the EC approval number: 2024-020. Moreover, this study has been conducted in accordance with the principles of the World Medical Association Declaration of Helsinki involving human participants (as revised in Brazil 2013).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Consent Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the participants for the collection of their samples and publication of their de-identified data and images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent to Publish declaration: not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData available on request from the authors: The data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosure\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare no Conflict of Interests for this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKF, MN and YT designed this study. KF, MN, YT, YS, HM, YK, YN, YW, ST, NM, MI, HT, TI, TU and HN collected and analyzed the data for the study. KF and MN prepared the manuscript. HN supervised the study. All authors are in agreement with the contents of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the patients and staff of Yamaguchi University Hospital for their participation in this study and Editage (www.editage.com) for the English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChan A, Kow A, Hibi T, Di Benedetto F, Serrablo A. Liver resection in cirrhotic liver: Are there any limits? Int J Surg. 2020;82:109\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurchard PR, Dave YA, Loria AP, Parikh NB, Pineda-Solis K, Ruffolo LI, Strawderman M, Schoeniger LO, Galka E, Tomiyama K, Orloff MS, Carpizo DR, Linehan DC, Hernandez-Alejandro R. Early postoperative ERAS compliance predicts decreased length of stay and complications following liver resection. HPB (Oxford). 2022;24:1425\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, Carter T, Cassidy CL, Chittenden EH, Degenhardt E, Griffith S, Manworren R, McCarberg B, Montgomery R, Murphy J, Perkal MF, Suresh S, Sluka K, Strassels S, Thirlby R, Viscusi E, Walco GA, Warner L, Weisman SJ, Wu CL. 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J Anesth. 2014;28:554\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStamenkovic DM, Jankovic ZB, Toogood GJ, Lodge JP, Bellamy MC. Epidural analgesia and liver resection: postoperative coagulation disorders and epidural catheter removal. Minerva Anestesiol. 2011;77:671\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTzimas P, Prout J, Papadopoulos G, Mallett SV. Epidural anaesthesia and analgesia for liver resection. Anaesthesia. 2013;68:628\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ (Clinical Res ed. 2015;350:g6380.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCarthy M. Opioids should be last resort to treat chronic pain, says draft CDC guideline. BMJ (Clinical Res ed. 2015;351:h6905.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGan TJ. 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J Hepatobil Pancreat Sci. 2021;28:297\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurphy V, Koea J, Srinivasa S. The efficacy and safety of acetaminophen use following liver resection: a systematic review. HPB (Oxford). 2022;24:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDieu A, Huynen P, Lavand'homme P, Beloeil H, Freys SM, Pogatzki-Zahn EM, Joshi GP, Van de Velde M. Pain management after open liver resection: Procedure-Specific Postoperative Pain Management (PROSPECT) recommendations. Reg Anesth Pain Med. 2021;46:433\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGill MR, Hinson JA. The development and hepatotoxicity of acetaminophen: reviewing over a century of progress. Drug Metab Rev. 2020;52:472\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAryaie AH, Lalezari S, Sergent WK, Puckett Y, Juergens C, Ratermann C, Ogg C. Decreased opioid consumption and enhance recovery with the addition of IV Acetaminophen in colorectal patients: a prospective, multi-institutional, randomized, double-blinded, placebo-controlled study (DOCIVA study). Surg Endosc. 2018;32:3432\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinoshita J, Fushida S, Kaji M, Oyama K, Fujimoto D, Hirono Y, Tsukada T, Fujimura T, Ohyama S, Yabushita K, Kadoya N, Nishijima K, Ohta T. A randomized controlled trial of postoperative intravenous acetaminophen plus thoracic epidural analgesia vs. thoracic epidural analgesia alone after gastrectomy for gastric cancer. Gastric Cancer. 2019;22:392\u0026ndash;402.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawakami J, Abe T, Higaki E, Hosoi T, Fukaya M, Komori K, Ito S, Nakatochi M, Nagino M, Shimizu Y. Scheduled intravenous acetaminophen versus nonsteroidal anti-inflammatory drugs (NSAIDs) for better short-term outcomes after esophagectomy for esophageal cancer. Surg Today. 2020;50:1168\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaniguchi H, Takenouchi M, Imaura M, Nagahuchi M, Tachibana H, Kamada T, Suga K, Sato T, Honda K, Egawa T. Postoperative scheduled intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy in Japan. Mathews J Anesth. 2018;34:502\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhkura Y, Haruta S, Shindoh J, Tanaka T, Ueno M, Udagawa H. Effectiveness of postoperative intravenous acetaminophen (Acelio) after gastrectomy: A propensity score-matched analysis. Med (Baltim). 2016;95:e5352.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhkura Y, Shindoh J, Ueno M, Iizuka T, Haruta S, Udagawa H. A new postoperative pain management (intravenous acetaminophen: Acelio\u0026reg;) leads to enhanced recovery after esophagectomy: a propensity score-matched analysis. Surg Today. 2018;48:502\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdachi T, Hara T, Matsushima H, Soyama A, Eguchi S. Essential updates 2022/2023: A review of current topics in robotic hepatectomy. Ann Gastroenterol Surg. 2024;8:774\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCassese G, Han HS, Lee E, Lee B, Lee HW, Cho JY, Montalti R, Troisi RI. Laparoscopic versus open liver resection for multiple hepatocellular carcinoma within and beyond the Milan criteria: An Eastern-Western propensity score-matched analysis. J Hepatobiliary Pancreat Sci. 2024;31:2\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO'Neill A, Lirk P. Multimodal analgesia. Anesthesiol Clin. 2022;40:455\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChandrakantan A, Glass PS. Multimodal therapies for postoperative nausea and vomiting, and pain. Br J Anaesth. 2011;107(Suppl 1):i27\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eApfel CC, Heidrich FM, Jukar-Rao S, Jalota L, Hornuss C, Whelan RP, Zhang K, Cakmakkaya OS. Evidence-based analysis of risk factors for postoperative nausea and vomiting. Br J Anaesth. 2012;109:742\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKıtlık A, Erdogan MA, Ozgul U, Aydogan MS, Ucar M, Toprak HI, Colak C, Durmus M. Ultrasound-guided transversus abdominis plane block for postoperative analgesia in living liver donors: A prospective, randomized, double-blinded clinical trial. J Clin Anesth. 2017;37:103\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBotting RM. Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clin Infect Dis. 2000;31(Suppl 5):S202\u0026ndash;210.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006;79:371\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Acetaminophen, Analgesics, Opioid, Postoperative Nausea and Vomiting, Minimally invasive hepatectomy","lastPublishedDoi":"10.21203/rs.3.rs-6533986/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6533986/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEffective postoperative pain management is crucial after minimally invasive hepatectomy (MIH) to promote recovery, and multimodal analgesia strategies are used to reduce opioid requirements and improve outcomes. Multimodal therapies for postoperative pain management commonly comprise acetaminophen. However, the safety and efficacy of acetaminophen for postoperative analgesia in minimally invasive hepatectomy remains unestablished due to its hepatic metabolism. This study aimed to evaluate the safety and analgesic efficacy of routine intravenous acetaminophen administration following MIH.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe data of consecutive 50 participants who had undergone MIH were retrospectively analyzed. Regarding postoperative analgesia, participants were assigned to either the opioid-alone cohort (Cohort O) or opioid with routine intravenous acetaminophen cohort (Cohort A). Analgesic efficacy was evaluated using the numerical rating scale (NRS) over the first 2 postoperative days. The sum of opioid rescue doses and frequency of postoperative nausea and vomiting (PONV) were assessed. Analgesic safety was determined by monitoring prolonged elevated transaminase levels.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePostoperatively, no statistically significant differences in the hepatic and renal functions and systemic inflammatory markers were observed between the two cohorts. On both postoperative day 1 and day 2, Cohort A showed lower NRS scores compared with Cohort O. Notably, almost all patients in Cohort A did not require any rescue opioid doses, resulting in a significantly reduced median rescue dose (6 versus 0 doses, p\u0026thinsp;=\u0026thinsp;0.0017). Even when opioid doses were reduced due to PONV, Cohort A continued to exhibit significantly lower NRS scores.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eMultimodal analgesia comprising the routine intravenous acetaminophen administration could be safe and effective after minimally invasive hepatectomy, without adverse effects regarding hepatic function.\u003c/p\u003e","manuscriptTitle":"Routine Use of Intravenous Acetaminophen Safely Enhances Pain Control After Minimally Invasive Hepatectomies: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-03 07:13:35","doi":"10.21203/rs.3.rs-6533986/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-11T16:01:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-07T15:55:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-02T22:58:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3680374342847725128705659947234033104","date":"2025-06-25T11:20:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239941817767572058391471813096122961524","date":"2025-06-24T21:36:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-10T01:16:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30349750137124756711054810331261415792","date":"2025-05-31T15:41:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-28T15:57:10+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-06T09:58:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-06T06:45:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-06T06:44:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2025-04-26T09:07:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"60208147-31f3-439a-b7e3-a74a81afcd76","owner":[],"postedDate":"June 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:00:21+00:00","versionOfRecord":{"articleIdentity":"rs-6533986","link":"https://doi.org/10.1186/s12893-025-03169-0","journal":{"identity":"bmc-surgery","isVorOnly":false,"title":"BMC Surgery"},"publishedOn":"2025-10-03 15:57:10","publishedOnDateReadable":"October 3rd, 2025"},"versionCreatedAt":"2025-06-03 07:13:35","video":"","vorDoi":"10.1186/s12893-025-03169-0","vorDoiUrl":"https://doi.org/10.1186/s12893-025-03169-0","workflowStages":[]},"version":"v1","identity":"rs-6533986","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6533986","identity":"rs-6533986","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}