This study was performed in strict accordance with the principles outlined in the Declaration of Helsinki. All research procedures were reviewed and approved by the Ethics Committee of The First Hospital of Jiaxing (approval No.: 2023-LY-123; approval date: March 29, 2023; see Supplementary File 1 for the official ethics approval document). A waiver of informed consent was granted due to the retrospective nature of the study, use of de-identified data, and minimal risk to participants. Details of the materials, equipment, and software used in this study are provided in the Table of Materials.
Study design
This work presents a single-center retrospective cohort study conducted at The First Hospital of Jiaxing between March 2024 and March 2025. A total of 350 elderly patients who underwent major abdominal surgery were screened for eligibility. Of the included patients, thirty-two individuals were omitted due to incomplete clinical data, including 10 cases lacking preoperative frailty assessment results, 10 with missing documentation regarding PPC occurrence, 7 missing visual analogue scale (VAS) pain scores on the first postoperative day, and 5 without assess respiratory risk in surgical patients in Catalonia (ARISCAT) scores. Additional exclusions comprised 5 cases of acute myocardial infarction, 2 cases of severe pneumonia, 5 cases of advanced heart failure, 5 patients who received intraoperative tracheotomy, 2 cases of malignant tumor, 2 cases of end-stage uremia, and 3 cases of severe pulmonary fibrosis. Subsequent to exclusion of ineligible patients, a total of 294 patients were finally enrolled in the analysis. Based on whether PPCs occurred during hospitalization, enrolled patients were categorized into the PPCs group (n = 53) and the non-PPCs group (n = 241) (Figure 1).
Inclusion criteria
Patients aged 65 years or older who received major abdominal operations, including radical gastrectomy, radical colorectal cancer resection, cholecystectomy, pancreatic surgery, and intestinal obstruction lysis, with body mass index between 17.5 and 29.0 kg/m2 and an American Society of Anesthesiologists physical status of Grade I to III18. Both laparoscopic and open major abdominal procedures were included.
Emergency surgery was explicitly defined as surgery performed within 24 h after admission or after the acute onset of the condition requiring operative intervention, as documented in the electronic medical record. This definition was intended to capture procedures that could not be postponed for further preoperative optimization and corresponds to the "emergency" category rather than the "urgent" or "semi-urgent" categories. Urgent or semi-urgent procedures, defined as surgery performed more than 24 h but within 72 h after admission, and elective procedures, defined as surgery scheduled in advance after adequate preoperative preparation, were not classified as emergency surgery. In the present cohort, all patients classified as undergoing emergency surgery met the 24 h criterion, and no patients with urgent or semi-urgent procedures were included in the emergency surgery group. The interval between admission and surgery was extracted from the electronic medical record and anesthesia information system for each patient. Because emergency surgery is a major variable in both the primary multivariable analysis and the interaction analysis, this operational definition was pre-specified prior to data analysis and applied uniformly to all patients.
Exclusion criteria
Patients complicated with severe comorbidities including preoperatively active and severe respiratory diseases such as severe pneumonia, hepatic, renal, cardiovascular or cerebrovascular diseases; patients with severe preoperative pneumonia were excluded because an active, uncontrolled pulmonary infection at baseline would substantially confound preoperative frailty assessment and the attribution of postoperative pulmonary complications to emergency surgery and frailty; individuals with stage IV malignant tumors accompanied by extensive distant metastases confirmed by imaging or pathology19; subjects missing core clinical and follow-up data involving frailty evaluation, ARISCAT score, postoperative day 1 VAS pain score or PPC records; patients receiving preoperative or intraoperative pulmonary interventions, or requiring postoperative ICU admission with respiratory support within 24 h for non-pulmonary issues; people suffering from severe mental illnesses or significant cognitive dysfunction; those treated with immunosuppressants two months before surgery; and patients with perioperative blood loss over 2000 mL or an operation time longer than 10 h20. Major abdominal operations were defined as open or laparoscopic abdominal procedures performed under general anesthesia, involving gastrointestinal, hepatobiliary-pancreatic, splenic, or retroperitoneal surgery, with expected moderate-to-high surgical trauma, substantial perioperative physiological disturbance, and a typical operative duration of at least 60 min. Minor procedures such as simple appendectomy, diagnostic laparoscopy, and superficial abdominal wall surgery were not included.
These exclusion criteria were applied to improve internal homogeneity and to reduce confounding by severe baseline cardiopulmonary, renal, hepatic, or neurological disease, stage IV malignancy, major intraoperative blood loss, prolonged operative time, and postoperative ICU respiratory support. However, it should be acknowledged that these criteria also produce a relatively selected elderly population. In particular, elderly patients requiring emergency abdominal surgery who also have severe systemic illness may be precisely the group in whom frailty and emergency surgery are most clinically relevant, and such patients were largely excluded from the present cohort. Therefore, the findings of this study should be generalized with caution to the broader population of elderly patients undergoing major abdominal surgery, especially those with severe comorbidities or extreme perioperative risk profiles.
Diagnostic criteria for PPCs
Diagnosis of PPCs was established in accordance with the official guideline released by the European Joint Task Force in 202121. Patients were diagnosed with PPCs if they met any one of the listed criteria (Table 1). For the primary association analysis, only PPCs occurring after the postoperative day-1 VAS assessment were considered as outcomes, so that the temporal sequence between the postoperative predictor and the outcome was unambiguous. PPCs that occurred before or at the time of the VAS assessment were not counted as events in the primary analysis. The exact timing of PPC onset relative to surgery and to the VAS assessment was extracted from the electronic medical record, and the interval between the VAS assessment and PPC onset was calculated for each case.
Frailty assessment criteria
Preoperative frailty was evaluated using the Fried Frailty Phenotype scale22. This instrument defines frailty based on assessments across five domains. Patients were classified as frail if they met three or more criteria, as pre‑frail if one or two criteria were present, and as robust if none of the criteria were fulfilled (Table 2).
Data extraction
Data were retrospectively collected by two uniformly trained investigators from the hospital’s electronic medical record system, anesthesia information system, and laboratory and imaging databases for a total of 294 elderly patients who underwent major abdominal surgery between March 2024 and March 2025. Baseline characteristics, including sex, age, BMI, ASA physical status, educational level, smoking history, alcohol consumption history, hypertension, diabetes mellitus, coronary heart disease, symptomatic stroke, surgical site, metabolic equivalents (METs), preoperative peripheral capillary oxygen saturation (SpO₂), preoperative hemoglobin (Hb), preoperative white blood cell count (WBC), and preoperative albumin (ALB), were extracted from medical records obtained within 72 h before surgery. Frailty status and ARISCAT score were obtained from anesthesia preoperative evaluation documents completed within 24 h prior to the operation. Information regarding emergency versus elective surgery, intraoperative blood loss, fluid infusion volume, anesthesia duration, and operative time was gathered from intraoperative and anesthesia records on the day of surgery. The VAS pain score on the first postoperative day was derived from pain assessments performed within 24 h after surgery and before any confirmed PPC events. The occurrence of PPCs was defined as the first confirmed event during hospitalization occurring after the postoperative day-1 VAS assessment, based on which patients were categorized into the PPCs group (n = 53) and non-PPCs group (n = 241). Information regarding emergency versus elective surgery, including the exact time of admission, the time of surgery, and the interval between admission and surgery, was gathered from intraoperative and anesthesia records on the day of surgery. Patients were classified as undergoing emergency surgery only if the interval between admission and surgery was within 24 h; patients whose surgery was performed more than 24 h after admission were classified as undergoing elective or non-emergency surgery. After data collection, all entries were independently cross‑checked and organized by the two researchers to ensure accuracy and completeness.
Outcome measures
Height and body weight were measured using a mechanical height-weight scale, and BMI was calculated accordingly. SpO₂ was measured with a finger-clip pulse oximeter. For hematological testing, fasting peripheral venous blood (5 mL) was sampled from each patient and collected in anticoagulant tubes. Hb and WBC were determined in whole blood using an automated hematology analyzer. Another 5 mL sample of fasting venous blood was placed in serum-separating tubes without anticoagulant and centrifuged at 1500 × g for 10 min using a centrifuge to obtain serum. Serum ALB was then measured from the separated serum sample with an automated biochemical analyzer. Postoperative pain intensity was evaluated using VAS. Scores ranged from 0 to 10, with higher scores indicating more severe pain23. The VAS assessment was performed within the first 24 postoperative hours. To avoid reverse causation, the VAS score was treated as a postoperative variable rather than as a preoperative etiological risk factor. Only PPCs occurring after the VAS assessment were included in the primary analysis, and the time from surgery and from the VAS assessment to PPC onset was documented. The ASA physical status classification was assigned by attending anesthesiologists or senior physicians based on overall health and severity of comorbidities. Grade I was defined as a completely healthy individual with no systemic disease. Grade II indicated mild systemic disease without functional impairment. Grade III represented severe systemic disease with definite functional limitation. Grade IV referred to severe systemic disease that posed a constant threat to life. Grade V denoted a moribund patient unlikely to survive 24 h with or without surgery24. The ARISCAT score was completed by anesthesiologists. This scoring system included seven domains: age, preoperative SpO₂, recent respiratory infection within one month, preoperative anemia, surgical site, operative duration, and emergency surgery. The total possible score spanned 0 to 53, and a higher score indicated an increased risk of PPCs16. Data on operative time, anesthesia duration, intraoperative blood loss, fluid infusion volume, and METs were all retrieved from anesthesia records and perioperative nursing documents.
Sample size calculation
PPCs were set as the primary endpoint. The primary analysis of this study was multivariable logistic regression, on which a combined prediction model was further constructed. Therefore, the sample size justification should be aligned with prediction model development rather than with precision-based estimation of a single proportion. According to previous literature, the incidence of PPCs in elderly patients undergoing major abdominal surgery was reported to be approximately 11.3%25. In this study, the EPV (events per variable) rule, which is commonly used in clinical prediction model development, was adopted for sample size estimation. This rule requires at least 10 outcome events per predictor variable included in logistic regression. The final primary multivariable logistic regression model contained exactly eight fitted covariates, as reported in Table 3: age, ASA physical status ≥ Grade III, smoking history, diabetes mellitus, intraoperative fluid infusion volume, postoperative day 1 VAS pain score, emergency surgery, and preoperative frailty. No additional covariates, including the ARISCAT composite score or its non-overlapping components (preoperative SpO₂, recent respiratory infection, preoperative anemia, surgical site, and operative duration), were entered into the final fitted primary model. Therefore, the minimum required number of events was 8 × 10 = 80 PPC events. Based on the expected PPC incidence of 11.3%, the total sample size required to achieve 80 events was 80 ÷ 0.113 ≈ 708 cases. A total of 294 patients were actually enrolled in this study, among whom 53 developed PPCs, yielding an overall incidence of 18%. With 53 actual events corresponding to the eight fitted predictors in the primary model, the EPV was 6.6, which is below the conventional threshold of EPV ≥ 10. In addition, the interaction model included a further product term (emergency surgery × preoperative frailty) on top of age, emergency surgery, preoperative frailty, and postoperative day 1 VAS pain score, so the EPV for the interaction model was even lower than that for the primary model. This raises concerns regarding potential model instability and overfitting. Therefore, the apparent AUC of the combined prediction model should be regarded as a preliminary estimate in the derivation dataset rather than as a validated measure of predictive performance. The conclusions of this study are primarily based on effect estimates and their 95% confidence intervals; model stability and predictive performance still require further confirmation through internal and external validation. Future studies with larger sample sizes, sufficient event numbers, and formal internal and external validation are needed to confirm the robustness and generalizability of the combined prediction model.
Statistical analysis
Normality (Kolmogorov‑Smirnov test) and homogeneity of variance (Levene test) were first examined for all continuous variables. Data with normal distribution and homogeneous variance were presented as mean ± standard deviation (mean ± SD), and between‑group comparisons were performed using an independent samples t‑test. Non‑normally distributed data were expressed as median (interquartile range) [M (Q1, Q3)] and compared using the Mann‑Whitney U test. Categorical variables were reported as number (percentage) [n (%)] and analyzed using the chi‑square test; if the expected frequency was less than 5, Fisher’s exact test was applied instead.
Logistic regression analysis was conducted to identify independent factors associated with PPCs. The occurrence of PPCs (yes = 1, no = 0) was taken to be the dependent variable. The variables included in the multivariable logistic regression model were pre-specified based on clinical reasoning and prior literature, rather than selected solely based on univariable P values. Specifically, the predictors were chosen a priori because they are established or plausible factors associated with PPCs in elderly patients undergoing major abdominal surgery, including age, ASA physical status, smoking history, diabetes mellitus, intraoperative fluid infusion volume, postoperative day 1 VAS pain score, emergency surgery, and preoperative frailty. These variables were retained in the model irrespective of their univariable P values, so that the model would not be driven by data-dependent selection and to reduce the risk of unstable estimates and biased inference in a relatively small dataset. Accordingly, the final primary multivariable logistic regression model contained exactly eight covariates: age (continuous, years), ASA physical status ≥ Grade III (yes/no), smoking history (yes/no), diabetes mellitus (yes/no), intraoperative fluid infusion volume (continuous), postoperative day 1 VAS pain score (continuous), emergency surgery (yes/no), and preoperative frailty (yes/no). These eight variables are exactly the covariates reported in Table 3, and no additional covariates were entered into the primary model. Although the non-overlapping components of the ARISCAT score available in the dataset (preoperative SpO₂, recent respiratory infection, preoperative anemia, surgical site, and operative duration) were initially considered, they were not included in the final fitted primary model because of the limited number of PPC events (53 events) and the resulting concern regarding model instability and overfitting; the ARISCAT composite score was likewise not included because age and emergency surgery are constituent components of ARISCAT, and including the composite score together with its own constituents would create conceptual overlap and complicate the interpretation of the regression coefficients. The interaction model was specified separately from the primary model and included age, emergency surgery, preoperative frailty, postoperative day 1 VAS pain score, and the product term emergency surgery × preoperative frailty; the ARISCAT composite score was not included because emergency surgery is one of its constituent items. The main-effect estimates for emergency surgery and preoperative frailty reported in Table 4 were derived from this interaction model.
Univariable analyses were performed for descriptive purposes and to characterize between-group differences, but the univariable P value was not used as the sole criterion for entry into the multivariable model. Because age and emergency surgery are both components of the ARISCAT score, including the composite ARISCAT score, along with its individual components, in the same model would create conceptual overlap and complicate the interpretation of the regression coefficients. Therefore, the ARISCAT composite score was not included in the primary multivariable model. Instead, the non-overlapping components of ARISCAT available in the dataset, including age, preoperative SpO₂, recent respiratory infection, preoperative anemia, surgical site, and operative duration, were considered alongside emergency surgery, preoperative frailty, and postoperative day 1 VAS pain score. This specification avoids modeling a composite score simultaneously with its own constituents and allows the coefficient for emergency surgery to be interpreted as its independent association with PPCs rather than as an effect conditional on a score that already contains emergency surgery. A sensitivity analysis using the ARISCAT composite score instead of its individual components was not performed because the two specifications condition on different sets of covariates, and their coefficients are not directly comparable; the primary model was pre-specified to address the conceptual overlap issue. An interaction term “emergency surgery × preoperative frailty” was incorporated (both were binary variables: emergency surgery, yes = 1, no = 0; preoperative frailty, yes = 1, no = 0). To examine whether emergency surgery modifies the association between preoperative frailty and PPCs, the interaction model was specified without the ARISCAT composite score, because ARISCAT already contains emergency surgery as a constituent item, and its inclusion would make the interaction term difficult to interpret. The interaction model, therefore, included age, emergency surgery, preoperative frailty, postoperative day 1 VAS pain score, and the other non-overlapping components of ARISCAT available in the dataset.
Because the number of PPC events was relatively small (53 events) relative to the number of parameters in the multivariable and interaction models, the events-per-variable ratio was relatively low. This raises concerns regarding model instability and overfitting, and the regression coefficients and apparent predictive performance should therefore be interpreted with caution. The combined prediction model should be regarded as hypothesis-generating rather than as a validated risk-prediction tool, and future studies with larger samples and formal internal and external validation are needed to confirm the robustness of the estimates.
The statistical significance of the multiplicative interaction was evaluated using odds ratio (OR), 95% confidence interval (95% CI), and corresponding P values. Because the outcome was not rare (PPCs incidence approximately 18%), OR-based interaction measures were interpreted as measures of association rather than direct causal risk interaction. Additive interaction indices such as RERI, AP, and S were not reported because they could not be reproducibly derived from the fitted model with internal consistency. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of each indicator for PPCs. The area under the curve (AUC), sensitivity, and specificity were calculated to evaluate predictive performance. All statistical tests were two-sided, and P < 0.05 was considered statistically significant. The number of outcome events was relatively small (53 PPC events) relative to the complexity of the multivariable and interaction models. With several predictors, including age, ASA physical status, smoking history, diabetes mellitus, intraoperative fluid infusion volume, postoperative day 1 VAS pain score, emergency surgery, and preoperative frailty, the number of events per model parameter was relatively low. Although the traditional “10 events per variable” rule should not be treated as an absolute threshold, this sample size nonetheless raises a substantial concern regarding model instability and overfitting. The reported predictive performance of the combined model should therefore be regarded as apparent performance in the derivation dataset only; no internal validation, bootstrap correction, or optimism adjustment was performed, and the model's predictive performance may be overestimated.