Development of an individualized model for predicting postoperative delirium in elderly patients with hepatocellular carcinoma

Yan, Mingfang; Lin, Zhaoyan; Zheng, Huizhe; Lai, **glan; Liu, Yuming; Lin, Zhenmeng

doi:10.1038/s41598-024-62593-z

Development of an individualized model for predicting postoperative delirium in elderly patients with hepatocellular carcinoma

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Published: 22 May 2024

Volume 14, article number 11716, (2024)
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Development of an individualized model for predicting postoperative delirium in elderly patients with hepatocellular carcinoma

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Mingfang Yan¹^na1,
Zhaoyan Lin²^na1,
Huizhe Zheng¹,
**glan Lai³,
Yuming Liu⁴ &
…
Zhenmeng Lin¹

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Abstract

Postoperative delirium (POD) is a common complication in older patients with hepatocellular carcinoma (HCC) that adversely impacts clinical outcomes. We aimed to evaluate the risk factors for POD and to construct a predictive nomogram. Data for a total of 1481 older patients (training set: n=1109; validation set: n=372) who received liver resection for HCC were retrospectively retrieved from two prospective databases. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance. The rate of POD was 13.3% (148/1109) in the training set and 16.4% (61/372) in the validation set. Multivariate analysis of the training set revealed that factors including age, history of cerebrovascular disease, American Society of Anesthesiologists (ASA) classification, albumin level, and surgical approach had significant effects on POD. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.798 (95% CI 0.752–0.843) and 0.808 (95% CI 0.754–0.861) for the training and validation sets, respectively. The calibration curves of both sets showed a degree of agreement between the nomogram and the actual probability. DCA demonstrated that the newly established nomogram was highly effective for clinical decision-making. We developed and validated a nomogram with high sensitivity to assist clinicians in estimating the individual risk of POD in older patients with HCC.

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Hepatocellular carcinoma (HCC) ranks as the sixth most commonly diagnosed cancer and the third deadliest globally¹. Globally, the incidence rates of HCC exhibit a positive correlation with age, reaching their peak around the age of 75 years^2,3. Owing to rapid aging of the global population and a record-high average life expectancy, there is a growing incidence of older patients diagnosed with HCC^4,5.

Postoperative delirium (POD) is a prevalent and serious complication marked by acute and varying alterations in mental condition, attentional capabilities, and consciousness levels following liver resection^6,7,8. Studies have shown a correlation between POD and unfavorable consequences, including heightened mortality rates, extended hospital stays, and elevated medical costs. Additionally, POD may contribute to lasting and more substantial declines in cognitive functions and daily life activities^{9,10,11,12,13}.

Roughly one-third of POD cases are considered preventable, making it a suitable focus for surgical quality improvement endeavors^14,15. In practice, uniformly implementing all effective delirium prevention strategies for every older surgical patient throughout their perioperative course is often impractical, despite being theoretically possible. Given the resource constraints and infrequent implementation of these interventions in most centers, recommendations have been made to focus on identifying patients with the highest risk^16,17,18.

Previous research has established nomograms for POD in malignant tumors, including gynecologic cancers^{Full size image}

Discussion

The incidence of POD was 13.3% in the training set and 16.1% in the validation set. Consistent with prior research, Nomi et al. reported a POD rate of 14.2%²⁹. Yoshimura et al. found a POD rate of 17.0% in patients undergoing hepatectomy³⁰. However, Ishihara et al. reported a lower POD incidence of 7.5%⁶, and Chen et al. found this to be 8.4%³¹. Variability in POD rates may be attributed to several factors: a lack of consistent definitions and assessment methods for POD by researchers, the diverse clinical characteristics of patients, and inaccuracies in estimation owing to the use of retrospective research methods.

This research involved develo** and validating a new nomogram for predicting POD in older HCC patients. The model demonstrated strong capabilities in both discrimination and calibration, which showed its clinical value. The model's robustness was further enhanced by external validation, affirming its applicability across different patient groups and clinical settings. To our knowledge, this represents the inaugural predictive model for POD in individuals diagnosed with HCC.

Previous studies have indicated a correlation between the risk of POD and the emergence of postoperative complications^32,33. However, such data are not accessible before or during surgery and thus cannot be integrated into predictive models.

In this study, a significant correlation between advanced age and an increased risk of POD was observed. Older patients experience a decline in physical capabilities, brain tissue integrity, and stress response regulation, along with diminished levels of key central neurotransmitters like acetylcholine and epinephrine³⁴. Age-related constriction of blood vessels reduces cerebral oxygenation, which can potentially lead to postoperative cerebral impairment^35,36. Moreover, alterations in drug metabolism and response owing to aging may increase the adverse effects of medications, thereby increasing the likelihood of POD³⁷.

The present study identified that a history of cerebrovascular disease is an independent risk factor for POD. Cerebrovascular disease can lead to cognitive impairment, dementia, and neurocognitive deficits, which is postulated to increase delirium possibly through altered brain networks and a reduced ability to integrate sensory inputs³⁸. Long-term susceptibility to delirium should be regarded as an integral aspect of the overall cerebrovascular disease burden^39,40. Several studies have indicated that cognitive dysfunction and reduced functional capacity are associated with a heightened risk of POD^41,42,43.

The ASA physical status classification system is commonly applied to evaluate a patient's ability to withstand anesthesia, primarily based on their overall compromised health and the presence of multiple comorbidities⁴⁴. Research has indicated that an ASA classification ≥ 3 is associated with an increased risk of complications and decreased overall survival after hepatectomy^45,46,47. Our study indicated that an ASA classification ≥ 3 is a risk factor for POD, as evidenced in numerous studies on this topic^48,49,50,51. Whereas we found no statistically significant differences in common comorbidities such as diabetes and hypertension between the groups, it is considered that the cumulative impact of various comorbidities might heighten baseline vulnerability in older patients. This susceptibility, combined with the stress of surgery, could be a contributing factor to the development of POD^52,53.

Numerous research findings indicate that a lower patient albumin level increases their likelihood of experiencing POD, a conclusion that aligns with the findings of our study^{6,54,55,56,57}. Hypoalbuminemia affects drug metabolism, antioxidant defense, and toxin processing because albumin is the primary transport protein in blood plasma. Reduced albumin levels may result in cognitive dysfunction owing to toxic effects and oxidative injuries^58,59. Appropriate medical intervention can yield lower albumin levels, potentially aiding in the reduction of POD risk.

This study showed that an open approach independently increases the risk of POD. A laparoscopic approach may reduce operative stress and postoperative systemic inflammation, which are known to be linked to the occurrence of POD^29,60,61,62.

There are a number of limitations in this study. First, this research was a retrospective evaluation conducted using a prospectively registered database. Recognizing the intrinsic biases inherent in this type of study design is crucial. Prior studies have highlighted several risk factors linked to POD, including preoperative depression and anxiety^{63,64,65,66,67,68}. Nevertheless, these factors were not incorporated into our analysis owing to certain constraints. Second, the experiment was conducted in only two centers, both of which are located in the same city. To further validate the model, it is necessary to use a more extensive sample size and conduct studies across various centers in different regions.

Conclusion

In older patients with HCC, factors such as age, cerebrovascular disease history, ASA classification, albumin levels, and the type of surgical procedure are identified as independent predictors of POD. In this study, we developed and externally validated a new, precise nomogram for personalized assessment and clinical decision-making.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by Fujian Cancer Hospital and Mengchao Hepatobiliary Hospital of Fujian Medical University. We thank Analisa Avila, MPH, ELS, of Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the language of a draft of this manuscript.

Funding

This work was supported by the Startup Fund for scientific research, Fujian Medical University (grant number: 2022QH1158); Natural Science Foundation of Fujian Province (grant number: 2020J011151, 2023J011280); Fujian Cancer Hospital Project (Grant number: 2024YN01).

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These authors contributed equally: Mingfang Yan and Zhaoyan Lin.

Authors and Affiliations

Department of Anesthesiology, Clinical Oncology School of Fujian Medical University &, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China
Mingfang Yan, Huizhe Zheng & Zhenmeng Lin
College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China
Zhaoyan Lin
Department of Infectious Diseases, Mengchao Hepatobiliary Hospital of Fujian. Medical University, Fuzhou, 350025, Fujian, China
**glan Lai
Department of Anesthesiology, Mengchao Hepatobiliary Hospital of Fujian. Medical University, Fuzhou, 350025, Fujian, China
Yuming Liu

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Mingfang Yan
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Zhaoyan Lin
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Huizhe Zheng
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**glan Lai
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Yuming Liu
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Zhenmeng Lin
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Contributions

Mingfang Yan collected the data and helped prepare the tables. Zhaoyan Lin contributed to the manuscript writing and revision. Huizhe Zheng contributed to the idea and design. Lai **glan designed the study and drew the figures. Yuming Liu collected the data and drafted the initial manuscript. Lin Zhenmeng collected the data and revised the manuscript.

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Yan, M., Lin, Z., Zheng, H. et al. Development of an individualized model for predicting postoperative delirium in elderly patients with hepatocellular carcinoma. Sci Rep 14, 11716 (2024). https://doi.org/10.1038/s41598-024-62593-z

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Received: 11 January 2024
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DOI: https://doi.org/10.1038/s41598-024-62593-z
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Development of an individualized model for predicting postoperative delirium in elderly patients with hepatocellular carcinoma

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Development of an individualized model for predicting postoperative delirium in elderly patients with hepatocellular carcinoma

Abstract

Similar content being viewed by others

Development and validation of a nomogram to predict postoperative delirium in older patients after major abdominal surgery: a retrospective case-control study

Nomogram for predicting the risk of postoperative delirium in elderly patients undergoing orthopedic surgery

Prediction model for delirium in patients with cardiovascular surgery: development and validation

Discussion

Conclusion

Data availability

References

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