DOI: https://doi.org/10.21203/rs.3.rs-2689225/v1
Inadequate postoperative analgesia is related to increased risks of many postoperative complications, prolonged hospital stay, declined quality of life, and increased costs.
This study investigated the risk factors for moderate-to-severe postoperative pain during the first 24 hours and 24–48 hours after major hepatobiliary pancreatic surgery.
Data of patients who underwent surgery at the Department of Hepatobiliary Surgery in Henan Provincial People's Hospital were collected from January 2018 to August 2020. Univariate and multivariate logistic regression analyses were used to identify the risk factors of postoperative pain.
In total, 2,180 patients were included in the final analysis. 183 patients (8.4%) suffered moderate-to-severe pain within 24 hours after operation. The independent risk factors associated with moderate-to-severe pain 24 hours after procedures were younger age (OR, 0.97; 95% CI, 0.95 to 0.98, P < 0.001), lower BMI (OR, 0.94; 95% CI, 0.89 to 0.98, P = 0.018), open surgery (OR, 0.34; 95% CI, 0.22 to 0.52, P < 0.001), and postoperative analgesia protocol with sufentanil (OR, 4.38; 95% CI, 3.2 to 5.99, P < 0.001). Postoperative hospital stay was longer in patients with inadequate analgesia (P < 0.05).
Age, BMI, laparoscopic surgery, and different analgesic drugs were significant predictors of postoperative pain after major hepatobiliary and pancreatic surgery.
Chinese Clinical Trial Registry ChiCTR2100049726
Pain is an unpleasant, subjective, sensory, and emotional experience. According to the current literature, approximately 30–55% of patients suffered moderate or severe pain on the day after surgery [1–3]. The management of postoperative pain is an important part in the patients’ recovery after operation. Inadequate postoperative analgesia is connected with a high risk of pulmonary and cardiac complications, excess opioid consumption, development of chronic pain, 30-day postoperative complications, prolonged hospital stays, patient dissatisfaction, readmissions, reduced quality of life, and increased spending [2–5]. Effective pain control can reduce postoperative complications, improve patient satisfaction, and be beneficial for patient recovery.
There are multiple reasons for postoperative pain, one of which is that some patients may have certain risk factors for developing more severe postoperative pain. Early identification of these risk factors for postoperative pain may facilitate personalized pain management strategies and prevent unintended distress in patients. Several literatures reported factors about severe postoperative pain, including demographic, psychosocial, and a number of clinical factors [4, 5]. But, few has analyzed the associated postoperative pain risk factors for major hepatobiliary pancreatic surgeries (without cholecystectomy alone). In this study, a retrospective case-control method was used to analyze associated risk factors of moderate-to-severe postoperative pain at 24 hours and 24–48 hours after major hepatobiliary and pancreatic surgery in a hospital in China. Basis our findings, anesthesiologists can be informed to distinguish patients at high risk of developing moderate to severe pain postoperatively, to intervene in advance, and to closely monitor and reduce the occurrence of pain, which would be helpful in patient recovery.
This single-center, retrospective study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital [Ethics approval number: (2021) lun shen (100)], an academic tertiary hospital in Zhengzhou, China. Written informed patient consent was waived by reason of the retrospective design and minimal intrusion to the privacy of the participants. The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2100049726) on 08/08/2021. Our case-control study report adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines [6]. All data were extracted from electronic medical records and analyzed anonymously. Patients who underwent surgery at the Department of Hepatobiliary Surgery in our hospital (Henan Provincial People's Hospital, Zhengzhou University People’s Hospital) between January 2018 and August 2020 were included in this study.
The inclusion criteria were as follows: (1) 18 years ≤ age < 75 years, (2) American Society of Anesthesiologists (ASA) class I-III, and (3) patients undergoing elective operation with general anesthesia. The exclusion criteria were as follows: (1) patients with multiple surgeries, (2) patients who were transferred to the intensive care unit (ICU) postoperatively, (3) patients without patient controlled intravenous anesthesia (PCIA) or with different analgesia regimens, and (4) patients undergoing cholecystectomy only.
The protocol for anesthesia was implemented in routine clinical practice. According to the preoperative fasting guidelines, patients fasted for both solids and fluids before surgery for at least 8 hours. A prophylactic antibiotic was administered 30 minutes prior to surgery. Upper extremity venous access was established, and blood pressure (BP), electrocardiogram (ECG), heart rate (HR), and pulse oximetry (SpO2) were routinely monitored. The anesthesiologist decided whether to perform a single-shot ultrasound-guided nerve block with 30–40 ml of 0.25–0.33% ropivacaine according to the site of surgery. The patients received premedication with 5 mg of dexamethasone and 0.5–1.0 mg of penehyclidine hydrochloride. All patients underwent general anesthesia with the same type of medication. Anesthesia was induced with 0.05 mg/kg of midazolam, 0.2–0.3 mg/kg of etomidate, 0.3–0.5µg/kg of sufentanil, and 0.15 mg/kg of cis-atracurium or 0.6–0.9 mg/kg rocuronium. Mechanical ventilation was performed after tracheal intubation using a visual laryngoscope with a tidal volume of 6–8 ml/kg and 12 breaths/minute. During maintenance of anesthesia, combined intravenous-inhalation anesthesia with propofol (4–6 mg/kg·h), remifentanil (0.2–0.5 µg/kg·min), and sevoflurane (1–3%) were administered to maintain the Bispectral Index (BIS) between 40 and 60. The infusion of muscle relaxants was stopped and 5 mg of tropisetron was infused intravenously 30 minutes before the end of surgery. Patients were transferred to the post-anesthesia care unit (PACU) for recovery after surgery. Neostigmine and tropine were used to antagonize residual neuromuscular block when necessary. The PCIA pump was attached to all the patients after surgery. It was mainly filled with 2.0–2.5 µg/kg of sufentanil or 8–10 mg of butorphanol with 1–1.5 µg/kg of dexmedetomidine and 10 mg of tropisetron. Additionally, 120–240 mg of Ketorolac Tromethamine was administered at the same time over the next 2 days. The background continuous rate was 2 ml/h, and the bolus dose was 2 ml with a 15 minute lockout interval. Patients with inadequate analgesia were advised to press the PCIA button, which was defined by a visual analog scale (VAS) ≥ 4.
Demographic characteristics (age, sex, body mass index [BMI], and educational level), comorbidities (hypertension, diabetes mellitus, coronary artery disease, and cerebral complications), ASA grade, history of anesthesia, and smoking were retrospectively collected. In this study, patients were considered to have a history of smoking if they had smoked every day for more than 1 year, regardless of whether they had quit perioperatively [7]. Intraoperative characteristics included the type of surgery, laparoscopic surgery, anesthetic methods (with or without nerve block), types of nerve block, duration of operation, anesthesia duration, intraoperative fluid volume, blood loss, urine volume, and blood transfusion. The postoperative days were also recorded. In our hospital, we recorded postoperative VAS scores during movement and at rest on postoperative day 1 (POD1) and postoperative day 2 (POD2) after operation, postoperative nausea and vomiting (PONV), and postoperative hospital stay days.
Patients’ pain was evaluated by acute pain services (APS) team members who were trained professionally, using a VAS at 24 and 48 hours postoperatively. A score of 0 indicates no pain and a score of 10 indicates the highest level of pain on the VAS scale.
Data were reported as mean ± standard deviation (SD) or median (interquartile range) for continuous variables and as frequency and percentage for categorical variables. Missing data of outcome variables and those with a missing ratio of more than 20% were deleted. For continuous features, a few missing values were imputed using mean imputation, whereas categorical values were imputed with dummy variables. Continuous variables were analyzed using unpaired Student’s t-test for normally distributed data or the Mann–Whitney U test. Categorical variables were analyzed using the χ2 test or Fisher’s exact test, as appropriate. Independent risk factors were identified using a multivariable logistic regression model that included preoperative and intraoperative variables with P < 0.15 in the univariable analysis and odds ratios (OR) and 95% confidence intervals (CI) were calculated. Statistical analyses were performed using the R Statistical Software (http://www. R-project. org, The R Foundation) and Free Statistics analysis platform, and P < 0.05 was considered to be statistically significant.
In total, 7,248 patients underwent hepatobiliary surgery during the study period. A total of 354 patients were excluded because of multiple surgeries (n = 354), incomplete electronic record information (n = 640), transfer to the ICU after surgery (n = 32), different postoperative analgesic regimens (n = 432), no follow-up within 24 hours after operation (n = 141), or no follow-up 48 hours after surgery (n = 2485). Patients who underwent cholecystectomy alone were excluded (n = 984), and finally 2,180 patients were included in the analysis (Fig. 1).
A total of 183 patients (8.4%) experienced moderate-to-severe pain 24 hours after operation. The baseline characteristics of the study participants are presented in Table 1. The characteristics of patients with or without moderate-to-severe pain within 24 hours after surgery were compared (Table 1). The average age was 55.4 ± 11.5 years and 58.0% of participants were male. In this group, 898 (41.1%) patients underwent partial hepatectomy, 184 (8.4%) underwent pancreatoduodenectomy, 238 (10.9%) underwent splenic and pancreatic surgery, 187 (8.6%) underwent surgery for cholangiocarcinoma and gallbladder cancer, 577 (26.5%) underwent surgery for choledocholithiasis, and 34 (1.6%) underwent other procedures. The incidence of moderate-to-severe pain in the patients was 8.4% during the first 24 postoperative hours with a mean VAS score of 5 (4, 6), whereas patients without moderate-to-severe pain had a mean VAS score of 0 (0, 1). The incidence of moderate-to-severe pain was 2.8% during the 24–48 postoperative hours. The incidences of PONV were significantly different between patients with and without insufficient analgesia 24 hours after surgery (P < 0.05).
| Variables | Total (n = 2180) | No Moderate-severe pain within 24 h (n = 1997) | Moderate-severe pain within 24 h(n = 183) | P values | |||||
|---|---|---|---|---|---|---|---|---|---|
| Gender, n (%) | 0.15 | ||||||||
| Male | 1265 (58.0) | 1168 (58.5) | 97 (53) | ||||||
| Female | 915 (42.0) | 829 (41.5) | 86 (47) | ||||||
| Age(y) | 55.4 ± 11.5 | 55.8 ± 11.3 | 51.1 ± 12.5 | < 0.001 | |||||
| BMI (kg/m2) | 23.7 ± 3.4 | 23.8 ± 3.4 | 23.2 ± 2.9 | 0.018 | |||||
| ASA | 0.023 | ||||||||
| I | 49 ( 2.2) | 44 (2.2) | 5 (2.7) | ||||||
| II | 1755 (80.5) | 1596 (79.9) | 159 (86.9) | ||||||
| III | 376 (17.2) | 357 (17.9) | 19 (10.4) | ||||||
| Smoking, n (%) | 0.4 | ||||||||
| No | 1391 (63.8) | 1269 (63.5) | 122 (66.7) | ||||||
| Yes | 789 (36.2) | 728 (36.5) | 61 (33.3) | ||||||
| Education level, n (%) | 0.429 | ||||||||
| Preliminary school | 968 (44.4) | 895 (44.8) | 73 (39.9) | ||||||
| Middle school | 762 (35.0) | 696 (34.9) | 66 (36.1) | ||||||
| College degree | 176 ( 8.1) | 157 (7.9) | 19 (10.4) | ||||||
| Bachelor degree | 105 ( 4.8) | 98 (4.9) | 7 (3.8) | ||||||
| Postgraduate | 169 ( 7.8) | 151 (7.6) | 18 (9.8) | ||||||
| History of anesthesia, n (%) | 0.014 | ||||||||
| No | 1161 (53.3) | 1056 (52.9) | 105 (57.4) | ||||||
| Yes | 805 (36.9) | 753 (37.7) | 52 (28.4) | ||||||
| NA | 214 ( 9.8) | 188 (9.4) | 26 (14.2) | ||||||
| Hypertension, n (%) | 0.005 | ||||||||
| No | 1688 (77.4) | 1531 (76.7) | 157 (85.8) | ||||||
| Yes | 492 (22.6) | 466 (23.3) | 26 (14.2) | ||||||
| Diabetes, n (%) | 0.133 | ||||||||
| No | 1900 (87.2) | 1734 (86.8) | 166 (90.7) | ||||||
| Yes | 280 (12.8) | 263 (13.2) | 17 (9.3) | ||||||
| Coronary artery disease, n (%) | 0.253 | ||||||||
| No | 2099 (96.3) | 1920 (96.1) | 179 (97.8) | ||||||
| Yes | 81 ( 3.7) | 77 (3.9) | 4 (2.2) | ||||||
| Cerebralcompicaton, n (%) | 0.605 | ||||||||
| No | 2106 (96.6) | 1928 (96.5) | 178 (97.3) | ||||||
| Yes | 74 ( 3.4) | 69 (3.5) | 5 (2.7) | ||||||
| Types of surgery, n (%) | 0.013 | ||||||||
| Hepatic resection | 897 (41.1) | 819 (41) | 78 (42.6) | ||||||
| Pancreatoduodenectomy | 184 ( 8.4) | 157 (7.9) | 27 (14.8) | ||||||
| Splenectomy and pancreatectomy | 238 (10.9) | 225 (11.3) | 13 (7.1) | ||||||
| Surger for Bile duct cancer and gallbladder cancer | 187 ( 8.6) | 169 (8.5) | 18 (9.8) | ||||||
| Choledocholithiasis | 577 (26.5) | 536 (26.8) | 41 (22.4) | ||||||
| Other surgery | 97 ( 4.4) | 91 (4.6) | 6 (3.3) | ||||||
| Laparoscopic surgery, n (%) | < 0.001 | ||||||||
| No | 1436 (65.9) | 1280 (64.1) | 156 (85.2) | ||||||
| Yes | 744 (34.1) | 717 (35.9) | 27 (14.8) | ||||||
| Postoperative analgesia protocol, n (%) | < 0.001 | ||||||||
| Butorphanol | 1539 (70.6) | 1468 (73.5) | 71 (38.8) | ||||||
| Sufentanil | 641 (29.4) | 529 (26.5) | 112 (61.2) | ||||||
| Preoperative Hb (g/dL) | 126.1 ± 21.2 | 126.0 ± 21.4 | 127.9 ± 19.4 | 0.238 | |||||
| Perioperative blood transfusion, n (%) | 0.382 | ||||||||
| No | 1720 (78.9) | 1571 (78.7) | 149 (81.4) | ||||||
| Yes | 460 (21.1) | 426 (21.3) | 34 (18.6) | ||||||
| Anesthesia duration(min) | 249.7 ± 106.7 | 248.5 ± 106.9 | 262.1 ± 103.6 | 0.099 | |||||
| Surgery duration(min) | 235.2 ± 105.7 | 234.0 ± 105.9 | 248.0 ± 103.0 | 0.085 | |||||
| Anaesthetic methods, n (%) | 0.144 | ||||||||
| General anesthesia | 1943 (89.1) | 1774 (88.8) | 169 (92.3) | ||||||
| General anesthesia with nerve block | 237 (10.9) | 223 (11.2) | 14 (7.7) | ||||||
| Nerve block, n (%) | 0.395 | ||||||||
| No | 237 (10.9) | 223 (11.2) | 14 (7.7) | ||||||
| Thoracic nerve block | 1344 (61.7) | 1217 (60.9) | 127 (69.4) | ||||||
| Quadratus lumborum block | 281 (12.9) | 261 (13.1) | 20 (10.9) | ||||||
| TAP | 194 ( 8.9) | 181 (9.1) | 13 (7.1) | ||||||
| Rectus sheath block | 90 ( 4.1) | 84 (4.2) | 6 (3.3) | ||||||
| Others | 34 ( 1.6) | 31 (1.6) | 3 (1.6) | ||||||
| Preoperative days (d) | 5.5 ± 3.8 | 5.5 ± 3.9 | 5.2 ± 3.2 | 0.232 | |||||
| Postoperative days (d) | 11.5 ± 5.7 | 11.4 ± 5.7 | 12.7 ± 6.0 | 0.004 | |||||
| VAS at rest | 1.0 (0.0, 2.0) | 0.0 (0.0, 1.0) | 5.0 (4.0, 6.0) | < 0.001 | |||||
| VAS at movement | 2.0 (1.0, 3.0) | 2.0 (1.0, 3.0) | 6.0 (5.0, 7.0) | < 0.001 | |||||
| Postoperative nausea ,n (%) | 50 ( 2.3) | 41 (2.1) | 9 (4.9) | 0.033 | |||||
| Postoperative vomiting, n (%) | 29 ( 1.3) | 23 (1.2) | 6 (3.3) | 0.03 | |||||
Table 1 ( is placed at the end of the document )
In univariate analysis, moderate-to-severe pain 24 hours after operation was associated with younger age, lower BMI, open surgery, hypertension, pancreatoduodenectomy, and postoperative analgesia with sufentanil (Table 2). In multivariable analysis, the independent risk factors associated with moderate-to-severe pain 24 hours after operation included younger age (OR, 0.97; 95% CI, 0.95 to 0.98, P < 0.001), lower BMI (OR, 0.94; 95% CI, 0.89 to 0.98, P = 0.018), open surgery (OR, 0.34; 95% CI, 0.22 to 0.52, P < 0.001), and postoperative analgesia with sufentanil (OR, 4.38; 95% CI, 3.2 to 5.99, P < 0.001). As shown in Table 3, the independent risk factors for moderate-to-severe acute pain 24–48 hours after surgery were almost the same, except that BMI (OR, 0.93; 95% CI, 0.85 to 1.01, P = 0.708) was not included (Table 3).
| Variable | Univariate analysis | multivariable analysis | ||
|---|---|---|---|---|
| OR_95CI | P_value | OR_95CI | P_value | |
| Gender(F) | 1.25 (0.92 ~ 1.69) | 0.151 | 1.32(0.96 ~ 1.83) | 0.090 |
| Age(years) | 0.97 (0.96 ~ 0.98) | < 0.001 | 0.97(0.95 ~ 0.98) | < 0.001 |
| BMI (kg/m2) | 0.94 (0.9 ~ 0.99) | 0.018 | 0.94(0.89 ~ 0.98) | 0.016 |
| ASA I II | Reference 0.88 (0.34 ~ 2.24) | 0.784 | ||
| III | 0.47 (0.17 ~ 1.32) | 0.15 | ||
| Smoking No Yes | Reference 0.87 (0.63 ~ 1.2) | 0.401 | ||
| Education level Preliminary school Middle school | Reference 1.16 (0.82 ~ 1.65) | 0.395 | ||
| College degree | 1.48 (0.87 ~ 2.53) | 0.146 | ||
| Bachelor degree | 0.88 (0.39 ~ 1.95) | 0.746 | ||
| Postgraduate | 1.46 (0.85 ~ 2.52) | 0.171 | ||
| Historyof anesthesia, n (%) | 1.05(0.99 ~ 1.11) | 0.104 | ||
| Hypertension | 0.54 (0.35 ~ 0.83) | 0.005 | ||
| Diabetes | 0.68 (0.4 ~ 1.13) | 0.136 | ||
| CHD | 0.56 (0.2 ~ 1.54) | 0.26 | ||
| Cerebralcompicaton1 | 0.78 (0.31 ~ 1.97) | 0.606 | ||
| Types of surgery, n (%) Hepatic resection Pancreatoduodenectomy | Reference 1.81 (1.13 ~ 2.89) | 0.014 | 0.92(0.84 ~ 1.01) | 0.086 |
| Splenectomy and pancreatectomy | 0.61 (0.33 ~ 1.11) | 0.106 | ||
| Surger for Bile duct cancer and gallbladder | 1.12 (0.65 ~ 1.92) | 0.684 | ||
| Choledocholithiasis | 0.8 (0.54 ~ 1.19) | 0.275 | ||
| Other surgery | 0.69 (0.29 ~ 1.63) | 0.401 | ||
| Laparoscopic surgery, n (%) | 0.31 (0.2 ~ 0.47) | < 0.001 | 0.34(0.22 ~ 0.52) | < 0.001 |
| Perioperative blood transfusion, n (%) | 0.84 (0.57 ~ 1.24) | 0.383 | ||
| Preoperative days (d) | 0.97 (0.93 ~ 1.02) | 0.23 | ||
| Anesthesia duration(min) | 1 (1 ~ 1) | 0.099 | ||
| Surgery duration(min) | 1 (1 ~ 1) | 0.086 | ||
| Postoperative analgesia protocol, n (%) Butorphanol Sufentanil | Reference 4.38 (3.2 ~ 5.99) | < 0.001 | 4.23(3.10 ~ 5.93) | < 0.001 |
| Anaesthetic methods, n (%) General anesthesia General anesthesia with nerve block | Reference 0.66 (0.38 ~ 1.16) | 0.146 | ||
| Nerve block, n (%) No Thoracic nerve block | Reference 1.66 (0.94 ~ 2.94) | 0.081 | ||
| Quadratus lumborum block | 1.22 (0.6 ~ 2.47) | 0.58 | ||
| TAP | 1.14 (0.52 ~ 2.5) | 0.735 | ||
| Rectus sheath block | 1.14 (0.42 ~ 3.06) | 0.798 | ||
| Others | 1.54 (0.42 ~ 5.67) | 0.515 | ||
| Variable | Univariate analysis | multivariable analysis | ||
|---|---|---|---|---|
| OR_95CI | P_value | OR_95CI | P_value | |
| Gender(F) | 0.86 (0.5 ~ 1.45) | 0.563 | ||
| Age(years) | 0.97 (0.95 ~ 0.99) | 0.002 | 0.97(0.95 ~ 0.99) | 0.010 |
| BMI (kg/m2) | 0.93 (0.86 ~ 1.01) | 0.077 | 0.93(0.85 ~ 1.01) | 0.708 |
| ASA I II | Reference 0.45 (0.14 ~ 1.49) | 0.192 | ||
| III | 0.29 (0.07 ~ 1.16) | 0.081 | ||
| Smoking | 1.27 (0.75 ~ 2.13) | 0.372 | ||
| Education level Preliminary school Middle school | Reference 1.17 (0.66 ~ 2.09) | 0.584 | ||
| College degree | 1.56 (0.67 ~ 3.67) | 0.306 | ||
| Bachelor degree | 0.73 (0.17 ~ 3.14) | 0.675 | ||
| Postgraduate | 0.68 (0.2 ~ 2.28) | 0.534 | ||
| History of anesthesia | 1.06(0.96 ~ 1.17) | 0.221 | ||
| Hypertension | 0.45 (0.2 ~ 0.99) | 0.046 | ||
| Diabetes | 1.2 (0.59 ~ 2.47) | 0.613 | ||
| CHD | 0.43 (0.06 ~ 3.15) | 0.408 | ||
| Cerebralcompicaton | 0.48 (0.07 ~ 3.47) | 0.464 | ||
| Types of surgery, n (%) Hepatic resection Pancreatoduodenectomy | Reference 1.87 (0.85 ~ 4.09) | 0.117 | ||
| Splenectomy and pancreatectomy | 1.1 (0.47 ~ 2.59) | 0.823 | ||
| Surger for Bile duct cancer and gallbladder | 1.21 (0.49 ~ 2.99) | 0.687 | ||
| Choledocholithiasis | 0.77 (0.38 ~ 1.56) | 0.471 | ||
| Other surgery | 0.77 (0.18 ~ 3.29) | 0.72 | ||
| Laparoscopy surgery, n (%) | 0.42 (0.22 ~ 0.82) | 0.011 | 0.47 (0.24 ~ 0.91) | 0.026 |
| Perioperative blood transfusion, n (%) | 1 (1 ~ 1) | 0.399 | ||
| Preoperative days (d) | 0.99 (0.93 ~ 1.07) | 0.876 | ||
| Anesthesia duration(min) | 1 (1 ~ 1) | 0.072 | ||
| Surgery duration(min) | 1 (1 ~ 1) | 0.067 | ||
| Postoperative analgesia protocol, n (%) Butorphanol Sufentanil | Reference 2.65 (1.58 ~ 4.43) | < 0.001 | 2.50 (1.48 ~ 4.21) | < 0.001 |
| Anaesthetic methods, n (%) General anesthesia General anesthesia with nerve block | 0.91 (0.39 ~ 2.14) | 0.826 | ||
| Nerve block, n (%) No Thoracic nerve block | Reference 1.24 (0.52 ~ 2.95) | 0.624 | ||
| Quadratus lumborum block | 0.84 (0.27 ~ 2.64) | 0.765 | ||
| TAP | 0.81 (0.23 ~ 2.91) | 0.748 | ||
| Rectus sheath block | 0.88 (0.17 ~ 4.42) | 0.872 | ||
| Others | 0 (0 ~ Inf) | 0.984 | ||
Table 2 and Table 2 ( are placed at the end of the document )
The incidence of moderate-to-severe acute operative pain 24 hours after surgery among different age groups (four quartile groups) and pain significantly declined with age. Moreover, 24 hours after surgery, pain increased in the group with BMI༜25 kg/m2 as compared to those with BMI ≥ 25 kg/m2 (Fig. 2).
The occurrence of moderate-to-severe pain within 24 hours was in connection with an increased incidence of nausea or vomiting with regards to early postoperative outcomes, but this association was not found within 24–48 hours. Postoperative hospital stay was longer in patients with inadequate analgesia (Table 4).
| Moderate-severe acute pain within 24 h | P | Moderate-severe acute pain within 24–48 h | P | ||||
|---|---|---|---|---|---|---|---|
| Yes | No | Yes | No | ||||
| Postoperative nausea | 9(4.9) | 41(2.1) | 0.033 | 3 (5) | 54 (2.5) | 0.205 | |
| Postoperative vomiting | 6 (3.3) | 23 (1.2) | 0.03 | 0 (0) | 11 (0.5) | 1 | |
| Postoperative days | 12.7 ± 6.0 | 11.4 ± 5.7 | 0.004 | 13.0 ± 6.2 | 11.5 ± 5.7 | 0.043 | |
In recent years, laparoscopy is being utilized frequently in various procedures. It could relieve postoperative pain and be beneficial to the patients’ recovery. However, hepatobiliary and pancreatic surgery (without cholecystectomy) are still the more traumatic types of abdominal surgeries. The extant literature on pain describes moderate-to-severe pain intensities of 42% on day 1 and 33% on day 2 after living donor hepatectomy [8]. Another study found that the incidence of postoperative pain after urological and hepatobiliary operation was 64.8% [9]. In our retrospective cohort study, the occurrence rate of moderate-to-severe pain was 8.4% in postoperatively of major hepatobiliary and pancreatic surgeries. This may be due to different population characteristics, types of operation, postoperative analgesia, and the analgesic drugs used. In addition, the relevant literature was studied several years ago, whereby enhanced recovery after surgery (ERAS) and multimodal analgesia programs were not used. Hence, the incidence of postoperative acute pain would be higher.
The other finding of this study is that age, BMI, laparoscopy, and different postoperative analgesic drugs are significant risk factors for postoperative pain following these surgeries.
Although many studies have confirmed that postoperative pain decreases with age [10, 11], some have found no age-related differences [12]. Therefore, it is unclear whether postoperative pain is associated with age. This study supported that younger people are more likely to experience postoperative pain, and the incidence of postoperative pain decreased by 3% with increasing age (OR, 0.97; 95% CI, 0.95 to 0.98). Furthermore, comparisons of groups with interquartile ranges also showed corroborating conclusions. This is perhaps related to changes in the inflammatory response, immune system, pain processing, autonomic nervous system, and pain regulation [13, 14]. Moreover, the thermal and mechanical thresholds measured on the skin using quantitative sensory testing (QST) was found to be increased in the elderly [15, 16].Furthermore, elderly patients may have a higher pain threshold and show increased sensitivity to opioids, which is related to pharmacokinetic and psychosocial mechanisms [17, 18]. Compared to articles with different conclusions, the differences may be due to the different types of operation and the small sample size of that literature.
Currently, the effect of BMI on postoperative pain remains unclear. Patients with a high BMI are more likely to experience postoperative pain in some literatures [19–21], while others have shown that there is no such relationship [22, 23]. As we know, there are no reports on the relationship between BMI and postoperative pain after major hepatobiliary pancreatic surgery. The results of this study suggest that the incidence of postoperative pain is higher in patients with low BMI. A 1 kg/m2 increase in BMI was associated with a decreased risk of postoperative pain by 6% (OR, 0.94; 95% CI, 0.89 to 0.98, P = 0.018), and the incidence rate of pain increased in the group with BMI < 25 kg/m2 24 hours after surgery. People with a normal body fat percentage may have a higher metabolic rate, more active enzymes in the body, and a faster metabolism of analgesics. Patients with a low BMI are mostly associated with frailty and are more likely to experience postoperative complications, leading to postoperative pain. Future studies should demonstrate possible mechanisms and causal associations in this regard.
In the current trial, the use of sufentanil for postoperative analgesia increased the risk of postoperative pain by 4.38 times (OR, 4.38; 95% CI, 3.2 to 5.99, P < 0.001) as compared with butorphanol. Furthermore, butorphanol is an opioid agonist-antagonist that induces analgesia mainly through κ agonist receptors. Like traditional opioids, butorphanol inhibits the upload of noxious stimuli in the spinal dorsal horn and activates the pain control circuit transmitted from the midbrain to the spinal dorsal horn via the rostral ventromedial region (RVM), resulting in analgesic effects. Furthermore, patients undergoing hepatobiliary surgery usually experience visceral pain caused by laparoscopic peritoneal stretching, intraoperative visceral pull, and visceral ischemia. Butorphanol is more effective in suppressing visceral pain, with a lower incidence of associated adverse effects such as vomiting, nausea, dizziness, and respiratory depression as compared to pure α-receptor agonists [24, 25].
In this study, cholecystectomy alone was excluded, mainly because the trauma, operation time, postoperative analgesia type, and postoperative pain incidence rate of this surgery were significantly different as compared to other surgery types; thus, the data for major hepatobiliary and pancreatic surgeries except cholecystectomy were analyzed.
Although females report greater postoperative pain in different procedures than males [10), this was not observed in the present cohort. Diabetes, educational level, and method for anesthesia were not associated with postoperative pain. Unfortunately, general anesthesia combined with nerve block did not result in a better postoperative analgesic effect. Considering that nerve block was generally performed before surgery in our center, the effect of the block failed to last for 24 hours after surgery. Rebound tenderness may have been triggered, so it did not show an inherent advantage in VAS score 24 hours after surgery. Relevant prospective trials should be conducted to verify the specific effects of nerve block.
The overall incidence of postoperative nausea and vomiting in patients was relatively low, mainly due to the extensive measures taken in our center such as volume repletion, prevention of the use of dexamethasone and tropisetron, and other measures. However, the incidence in patients with moderate-to-severe pain is higher, which may be related to laparoscopic surgery, opioid use, motion sickness, and other factors. Similar to other studies, we found that moderate-to-severe postoperative pain was associated with a longer postoperative hospital stay.
This study had some limitations. First, it was retrospective in nature. Confounding variables of pain such as relevant psychological disorders were not included in our study. Second, postoperative pain is an individual experience that involves psychosocial, environmental, and genetic factors. These limitations should be taken into account while attempting to predict pain.
In summary, age, BMI, surgical approach, and different analgesic drugs were significant predictors of postoperative pain after major hepatobiliary and pancreatic surgeries. Based on these findings, more individualized postoperative pain management strategies should be considered earlier, especially in younger patients with a lower BMI, and laparoscopic surgery should be chosen whenever possible.
American Society of Anesthesiologists class ：ASA
the intensive care unit ：ICU
patient controlled intravenous anesthesia ：PCIA
blood pressure ：BP
electrocardiogram ：ECG
heart rate ：HR
pulse oximetry ：SpO2
Bispectral Index ：BIS
post-anesthesia care unit ：PACU
visual analog scale ：VAS
body mass index ：BMI
postoperative day 1 ：POD1
postoperative day 2 ：POD2
postoperative nausea and vomiting ：PONV
acute pain services team ：APS
standard deviation ：SD
odds ratios ：OR
confidence intervals ：CI
enhanced recovery after surgery ：ERAS
quantitative sensory testing ：QST
rostral ventromedial region ：RVM
Ethics approval and consent to participate
This single-center, retrospective study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital [Ethics approval number: (2021) lun shen (100)], an academic tertiary hospital in Zhengzhou, China. Written informed patient consent was waived by reason of the retrospective design and minimal intrusion to the privacy of the participants, which was approved by the Medical Ethics Committee of Henan Provincial People's Hospital.
All methods were carried out in accordance with the ethical standards of the Declaration of Helsinki 1964 and its later amendments.
Consent for publication
Not applicable
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Conflicts of interest
None declared.
Funding
None declared.
Authors' contributions
Hui Zhang conceived the study. Hui Zhang and Yitian Yang substantially contributed to conception and design, analyzed and interpreted data. Jiaqiang Zhang and Lianzhong Zhang revised the manuscript critically for important intellectual content. Lulu Jiang, and Xiaodong Xu contributed to the materials/analysis tools. Hui Zhang acquired, analyzed and interpreted most of the data and drafted the article. Jiaqiang Zhang and Lianzhong Zhang revised the manuscript. All authors read and approved the final manuscript.
Acknowledgment
The authors would like to thank all the individuals who participated in this study. The authors thank Wenjing Dong and Zhiguang Ping for their technical assistance in data extraction and analysis. We would like to thank Editage (www.editage.cn) for English language editing.