Comparative outcomes of post-operative delirium after video-assisted thoracoscopic, robotic, and open thoracic surgery: a narrative review

Introduction

Post-operative delirium (POD) is the most common complication following thoracic surgery in older adults. Commonly defined as patients greater than 65 to 75 years old, POD risk for older adults is compounded by baseline frailty and pre-existing cognitive impairment risk factors (1-4). Beyond its immediate clinical impact, POD is independently associated with increased morbidity, one-year mortality, accelerated cognitive decline and progression to dementia (2,5,6). In the United States alone, delirium contributes an estimated $33 billion in annual healthcare expenditures, with per-patient costs frequently exceeding $40,000 (2,6-8). Against a backdrop of international demographic aging and a rapidly growing thoracic surgery volume, identifying modifiable perioperative contributors to POD has become an increasingly pressing public health priority (8,9).

Despite this clinical burden, evidence evaluating the impact of surgical approach on POD in thoracic procedures remains limited. Recent reviews focus largely on isolated perioperative interventions, such as regional anesthesia (Zhou et al., 2024), or broad geriatric behavioral management (Miller et al., 2022) (2,5). Minimally invasive approaches, including video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS), have been hypothesized to reduce POD risk through attenuated delirium pathophysiology incidence (10-12). However, data directly comparing these approaches with open thoracotomy in relation to delirium outcomes remains fragmented.

This narrative review seeks to address this gap by synthesizing current evidence on the association between surgical approach and POD incidence in thoracic surgery. We examined studies comparing VATS and RATS with open thoracotomy and their respective associations with delirium risk. Our aim is to contextualize surgical approach not just as an isolated variable, but as a modifiable component within a multifactorial perioperative strategy tailored to older adults. We present this article in accordance with the Narrative Review reporting checklist (available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-58/rc).

Methods

We conducted a narrative literature review to identify studies evaluating POD outcomes across VATS, RATS, and open thoracic procedures. A structured search was performed from inception through January 29, 2026 using keywords and MeSH terms related to POD, thoracic surgery, open surgery, VATS, and RATS in PubMed, Scopus, Embase, and Web of Science (Table 1, Figure 1).

Figure 1 Flowchart of research search results.

Eligible studies were English-language investigations that assessed POD-related outcomes across different thoracic operative approaches. Randomized controlled trials, prospective and retrospective cohort studies, cross-sectional analyses, and case series were included. Case reports, animal, editorials, and mixed postoperative cohorts where POD could not be independently distinguished were excluded. Titles and abstracts of all retrieved studies were screened independently by three reviewers (C.K.N., A.H.L., E.S.) followed by full-text assessment of eligible articles. Data capture was performed using Microsoft Excel (version 16.1). The primary outcome was the incidence of POD by operative approach in thoracic surgery. Secondary outcomes included hospital length of stay, analgesic and opioid requirements, pain scores, and measures of mobility and post-operative recovery.

Key contents and findings

Preoperative risk prediction and modifiable variables

Recent literature has emphasized moving away from evaluating isolated risk factors and toward the use of comprehensive predictive models and scoring systems for POD in thoracic surgery. The preoperative variables most consistently identified include frailty, baseline cognitive impairment, comorbidity burden, and systemic inflammation (3,13,14). Several validated models incorporate the Modified Frailty Index (mFI-11) and baseline cognitive assessments like the Mini-Mental State Examination (MMSE) to quantify individual neurocognitive vulnerability (3). Comorbidity burden, often captured by the Age-Adjusted Charlson Comorbidity Index (aCCI), has been independently associated with elevated POD risk, with incremental score increases correlating with progressively higher delirium incidence (15). More thoracic-specific tools, such as the Thoracic Delirium Index (TDI), incorporate both chronological age and objective inflammatory markers such as the Platelet-to-White Blood Cell Ratio (PWR) to reflect systemic inflammatory priming and neurocognitive susceptibility (16).

Importantly, these models also incorporate the magnitude of the surgical procedure by weighting associative variables such as surgical duration, estimated blood loss, and graded surgical risk classifications (1). Within this framework, surgical approach emerges as a clinically modifiable variable, one that, unlike age or baseline frailty, can be actively selected for to reduce the overall operative stress burden (15,17). By actively opting for a minimally invasive surgery (MIS) approach like RATS or VATS when technically feasible, the surgical team may potentially attenuate overall operative stress burden. This proactive reduction can then go on to potentially begin to offset non-modifiable dangers such as advanced age and frailty within the patient’s predictive risk calculation, but these specific associations have yet to be established within the key literature.

Minimally invasive versus open thoracic surgery: impact of surgical trauma

In esophagectomy cohorts, minimally invasive approaches were consistently associated with lower POD incidence compared to open surgery. Dezube et al. (2020), evaluated 378 esophagectomy patients (median age 64 years) and found that open surgical approaches (thoracotomy/laparotomy) carried more than double the risk of developing POD compared to minimally invasive techniques [odds ratio (OR) 2.66] (18). For their cohort, the unadjusted incidence of delirium was 30% in the open group, versus 14% in the minimally invasive group. Jeong et al. (2016) similarly found that in a propensity-matched cohort of esophagectomy patients, robot-assisted thoracoscopic approaches significantly lowered the incidence of POD compared to open transthoracic surgery (30% vs. 42%, OR 0.55) (19). However, translating these findings directly to pure thoracic procedures requires caution. These operations involve combining abdominal and thoracic surgical fields, yielding different surgical durations, nociceptive burdens, and physiological stress profiles. Consequently, we also reviewed pure thoracic surgeries to isolate the specific impact of thoracic operative approaches on neurocognitive outcomes.

In this focused context, large-scale data from pure thoracic cohorts suggests that the increased invasiveness of the surgical approach is associated with a higher risk for POD. Piwkowski et al. (2023) analyzed a propensity-matched cohort of 9,892 patients (median age 65) undergoing lobectomy for lung cancer, demonstrating that the open thoracotomy approach yielded more than double the POD incidence (1.7%) compared to the VATS approach (0.8%, P<0.001) (20). The protective effect of minimally invasive techniques appears additionally associative in older cohorts. De León et al. (2021) found that among adults aged ≥65 undergoing lobectomy, a minimally invasive approach was associated with a reduction in Grade III/IV complication rates sufficient to approximate the morbidity profile of patients under 65 years undergoing open thoracotomy—potentially suggesting that operative approach may be associated with a partial compensation for age-related physiological vulnerability (17).

Surgical duration and the resulting exposure to general anesthesia further distinguish these operative approaches. Kwon et al. (2017) evaluated 498 pure anatomic pulmonary resections across RATS, VATS, and open approaches (median age 65), noting that open thoracotomies required the longest mean operating room time (268 minutes) (12). Interestingly, RATS was associated with a statistically significant increase in operative duration than VATS (233 vs. 200 minutes, P=0.0016). Because prolonged operations expose the aging brain to extended periods of systemic inflammation and sedation, both of which are independently associated with neurocognitive decline, surgical duration remains an important modifiable variable in POD prevention.

VATS vs. RATS: an important clarifier

Building on these findings from Kwon et al., VATS and RATS are both commonly grouped under the same umbrella of MIS but may have important distinctions in their impact on delirium risk. These modalities differ meaningfully in domains that could independently influence delirium risk. For instance, RATS frequently requires longer operative durations and extended anesthetic exposure, which are aforementioned, independent predictors of POD (3,10,12,21). Furthermore, while RATS provides technical advantages including three-dimensional visualization and wristed instruments articulation, it carries its own learning curve, during which operative duration, tissue trauma, and blood loss may be transiently elevated (22-25). Additionally, while objective postoperative pain scores show broadly comparable values between VATS and RATS in available series, patient-reported recovery experience and quality of life trajectories may diverge, dimensions relevant to POD prevention that remain incompletely characterized (12). Given this, conclusions regarding the neuroprotective benefits of MIS may be driven predominantly by larger VATS cohorts and cannot be uniformly applied to robotic techniques; future studies should therefore disaggregate RATS from the broader MIS umbrella.

MIS and mechanisms for decreased delirium risk

These associations between minimally invasive approaches and reduced delirium risk are most consistently explained through two mechanistic pathways: attenuation of intraoperative blood loss and reduction of postoperative nociceptive burden. To this first point, major blood loss and subsequent transfusions have been found to be independently associated with systemic neuroinflammation and elevated POD risk, with proposed mechanisms including increased cytokine release and immune activation (1,11,26,27). A cross-sectional analysis of 175 thoracic surgery patients by Wang et al. (2024) found that for patients undergoing open thoracotomy (median age 60), the requirement of a blood transfusion was associated with an elevated relative risk of POD (RR 16.875, P=0.012) (15). By reducing tissue disruption and intraoperative blood loss, minimally invasive approaches may attenuate this transfusion-associated neuroinflammatory burden. Piwkowski et al. found that VATS lobectomy was associated with significantly lower transfusion rates than open thoracotomy (3.3% vs. 8.7%, P<0.001), alongside fewer reoperations for hemorrhage—findings that support a potential mechanistic association between operative approach, transfusion exposure, and downstream delirium risk for future investigation (20).

Second, minimally invasive techniques have been shown to be associated with decreased postoperative pain, which reduces reliance on systemic opioid agents independently associated, in turn, with delirium pathogenesis (20). Li et al. (2024), in developing the Thoracic Delirium Index for patients aged >60, identified elevated postoperative pain — measured by visual analogue score (VAS) over the first three postoperative days — as an independent predictor of POD (OR 1.589 per VAS increase) (16). By eliminating the need for rib-spreading and large chest wall muscle division, VATS and RATS might reduce this pain burden. Kwon et al. (2017) similarly evaluated their 498 pulmonary resection cases and found a statistically significant decrease in acute pain scores for minimally invasive procedure patients compared to open thoracotomy from postoperative day 4 onward (P=0.0004), with a sustained reduction in chronic postoperative numbness (12). Finally, Darr et al. (2017) found that patients undergoing robotic pulmonary resection experienced significantly lower pain at rest on postoperative days 3, 4, and 5 compared to those undergoing open thoracotomy (28). By reducing the nociceptive stimulus, minimally invasive techniques may lower systemic opioid requirements—thereby logically potentially attenuating a pharmacological contributor to delirium in older adults.

Caveats to MIS

While the mechanical benefits of MIS are well-supported, the surgical approach alone is not a panacea for all patients (9,29). Evidence suggests that the specific extent of surgery alone appears less predictive of POD than the physical approach and the patient’s baseline vulnerability. Yaguchi et al. (2024), analyzing 1,674 pure thoracic surgery patients (median age 76), found no statistically significant difference in POD risk when comparing lobectomies than the shorter duration wide wedge resections (30). Instead, the physical trauma from the surgical approach and the patient’s advanced age were the primary drivers; while their overall cohort incidence was 5.9%, the POD rate rose to 19.7% for patients aged 80 years or older. While smaller, highly selected cohorts—such as Fong et al., which found no significant POD rate difference between VATS and open surgery in septuagenarians (2.7% vs. 0%)—offer conflicting signals, the available evidence still supports an association between minimally invasive operative approach and lower POD incidence, particularly in patients of advanced age (18,31-34).

Variance in POD incidence

The reported incidence of POD following thoracic surgery varies across the literature, ranging from 1.5% to nearly 20%. This heterogeneity warrants mechanistic scrutiny and can be largely attributed to three primary clinical and methodological divergences in: baseline patient vulnerabilities, surgical complexity, and the method of delirium assessment.

First, baseline patient characteristics, such as age-related cognitive reserve and frailty, often differ across cohorts, confounding direct outcome comparisons. Within postoperative delirium literature, there is no single standardized definition for “older adults”. While a threshold of ≥60 years is frequently used as a starting point, and ≥65 years remains a traditional metric for the “elderly”, neurocognitive risk scales progressively (1,8,16,35,36). Many large-scale prospective cohorts purposefully use ≥70 years to isolate highly vulnerable populations, while specialized validation studies target populations ≥75 years to capture high burdens of baseline cognitive impairment (4,37,38). As a result, chronologic age often serves as a proxy for biological vulnerability; while overall cohort incidences may appear low, POD rates increase to nearly 20% for the “very elderly” aged ≥80 years (30,33). To accurately contextualize the evidence, the specific age parameters of cited cohorts should be weighted alongside their reported delirium incidence.

Second, variations in surgical complexity influence neurological risk. More invasive and prolonged procedures are consistently associated with higher baseline POD rates compared to less invasive, pure pulmonary resections (18,30). The procedural burden, reflected by extent of tissue trauma, surgical duration, and the need for intraoperative blood transfusions, serves as a major physiological stressor that can rapidly compromise a fragile cognitive reserve (1,15,39-41).

Another driver of POD incidence variance is the methodology and timing of delirium assessment. Retrospective studies relying on generalized adverse event reporting or unstandardized chart reviews routinely yield low incidence rates (e.g., 1.5%) (38,42,43). This may reflect a systemic underdiagnosis rather than a true clinical reality. Without structured cognitive testing, clinical staff relying on routine observation fail to detect the majority of POD cases, with false-negative rates exceeding 80% on the first postoperative day (2,39,44-46). This detection failure occurs because unstructured observation can be biased toward hyperactive, agitated presentations, leading to systematic under recognition of the hypoactive subtype (characterized by lethargy and inattention), which is the most prevalent presentation in older adults—as reported by American College of Surgeons (47).

Conversely, prospective studies utilizing validated, active screening tools, such as the Confusion Assessment Method (CAM), 3-Minute Diagnostic Confusion Assessment Method (3D-CAM), or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), report significantly higher and more accurate POD rates (38,48). The 3D-CAM, for instance, standardizes the diagnostic process through brief, specific cognitive tests, demonstrating a sensitivity of 95% and effectively capturing the easily missed hypoactive cases. Adoption of standardized, algorithmic bedside screening consistently administered by trained personnel is therefore potentially helpful for more accurate prognostication and incidence estimation, removing subjective assessor guesswork from the clinical pathway.

Pathophysiology

Understanding the mechanistic basis of postoperative delirium not only contextualizes its clinical variability but also provides a foundation for biomarker-driven risk stratification. The physical trauma of thoracic surgery triggers a systemic inflammatory response, releasing damage-associated molecular patterns (DAMPs) and pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) (49-51). This systemic stress degrades the vascular endothelial glycocalyx, increasing blood-brain barrier (BBB) permeability and allowing inflammatory mediators to cross into the central nervous system, which may impair neural networks involved in attention and cognition (14,52,53).

Within this pathway, specific biomarkers have emerged as clinically informative correlates of POD. Preoperatively, elevated systemic inflammation, indicated by the aforementioned, low PWR and elevated leukocyte counts, has been associated as an independent predictor of delirium vulnerability (54). Postoperatively, elevations in plasma TNF-α and neuroinjury markers such as Neurofilament Light (NFL) track closely with POD occurrence (55-57). By quantifying the degree of neuroinflammation and neuronal injury, these biomarkers help provide critical mechanistic evidence associating surgical trauma with potential cognitive decline, helping establish the groundwork required to develop targeted therapeutic strategies and future clinical trials.

A potential multifactorial surgical approach given POD’s multifactorial paradigm

POD is a multifactorial neurocognitive syndrome that should employ a comprehensive, systems-based prevention strategy rather than reliance on isolated interventions. Accordingly, mitigation efforts should be embedded within patient-centered, multidisciplinary care models and structured Enhanced Recovery After Surgery (ERAS) pathways (58,59). Preoperative optimization begins with risk stratification through Comprehensive Geriatric Assessments to characterize baseline frailty, cognitive reserve, and functional status. Targeted prehabilitation and proactive medication reconciliation, particularly the deprescribing of deliriogenic agents such as benzodiazepines, anticholinergics, and high-dose opioids, are additional, well-supported components of risk modification (2,60).

Intraoperatively, anesthetic and physiologic management play a pivotal role in attenuating delirium risk. Regional analgesic strategies, including thoracic paravertebral blocks, provide effective nociceptive control while reducing systemic opioid exposure and blunting the surgical stress response (5,11). Maintenance of hemodynamic stability, avoidance of sustained hypotension, and electroencephalographic-guided titration of anesthetic depth to prevent burst suppression are also supported strategies for neuroprotection in vulnerable older adults (50,61).

Postoperative care should prioritize non-pharmacologic, cognition-preserving interventions as foundational elements. Structured programs such as the Hospital Elder Life Program (HELP), implementation of strict sleep hygiene protocols, frequent reorientation, and early mobilization are among the non-pharmacologic interventions with the strongest associative evidence for reducing delirium incidence in all patients (62). Pharmacologic management should emphasize opioid-sparing, multimodal analgesia to minimize central nervous system adverse effects while ensuring adequate pain control (63).

Within this integrated ERAS framework, the choice of surgical approach functions as a central enabling variable. As described herein, minimally invasive techniques such as VATS and RATS surgeries area associated with reduced chest wall trauma, attenuated systemic inflammatory signaling, and decreased postoperative pain severity. This lower nociceptive burden could hypothetically facilitate more effective implementation of regional, opioid-sparing analgesic regimens and permit earlier, safer mobilization. Thus, operative technique is not an isolated determinant but, indeed, a potentially structural component that enhances the feasibility and effectiveness of the broader cognitive-sparing perioperative bundle.

Limitations

Several limitations should inform the interpretation of our conclusions. First, the available evidence is almost entirely observational, retrospective, and heterogeneous, which precludes firm causal inferences. Observed differences in delirium rates between surgical approaches may be partially attributable to confounding factors, such as baseline patient frailty, underlying comorbidities, variations in anesthetic strategy, surgeon experience, or unmeasured institutional perioperative practices, rather than the surgical technique alone. Second, our central findings rely primarily on a restricted evidentiary base: two retrospective studies limited to esophagectomy patients, and one prospective cross-sectional study with limited statistical power. These studies differ substantially in their patient populations, specific surgical procedures, delirium definitions and assessment methods, and whether POD was evaluated as a primary or secondary endpoint. Consequently, this small number of comparative studies limits the generalizability of our findings to the broader thoracic surgery population.

The retrospective and single-center nature of many of our primary studies increases the risk of selection bias, as many cases of delirium may go undetected in retrospective chart review. A major methodological limitation across these studies is the lack of standardized, systematic delirium assessment. Many investigations relied on retrospective chart review rather than repeated, validated evaluations such as the CAM or CAM-ICU. This reliance potentially increases the risk of underdiagnosis, particularly for the hypoactive subtype of delirium, which often goes unrecognized without active screening. Consequently, the reported POD rates in these retrospective studies likely underestimate the true incidence, which prospective investigations utilizing standardized assessments have shown can reach up to 40% (1). Ultimately, this widespread lack of standardized cognitive screening fundamentally weakens the reliability of any between-group comparisons regarding how specific surgical approaches impact delirium

Future directions

Older adults comprise a rapidly growing share of the thoracic surgical population, making it increasingly important to understand how different operative strategies influence high-risk outcomes such as POD (64). Current evidence suggests that minimally-invasive techniques such as VATS and RATS may attenuate delirium risk by limiting tissue trauma, dampening systemic inflammation, improving pain control—thereby reducing opioid exposure, promoting earlier mobilization, and shortening hospitalization. To definitively establish these relationships, however, there remains a need for multicenter, prospective studies that designate POD as a primary, rather than secondary, endpoint. Such investigations could mandate the use of validated delirium assessment tools, such as the CAM-ICU or 3D-CAM, administered at standardized intervals to capture both hyperactive and hypoactive subtypes reliably. Furthermore, future trial designs could strictly standardize anesthetic and multimodal analgesic protocols across treatment arms to minimize confounding variables, as well as chronological age and surgical complexity definitions. Collectively, this would transform the current associative evidence base into a grounded framework capable of informing targeted, evidence-based strategies for delirium prevention in older adults undergoing thoracic surgery.

Conclusions

Early studies of minimally invasive techniques, including VATS and RATS, have been associated with lower rates of POD compared to open approaches, potentially associated with reductions in surgical trauma, pain, opioid exposure, transfusion requirements, and length of hospitalization. Although current data are limited by small cohorts, heterogeneous delirium assessment methods, and a lack of randomized trials, the available evidence supports an association between minimally invasive techniques and reduced POD risk in older adults undergoing thoracic surgery. In clinical practice, the choice of surgical approach must be viewed as a modifiable, foundational component embedded within a broader, multidisciplinary geriatric care pathway. Future research should mandate multicenter, prospective designs utilizing standardized delirium measures (such as the 3D-CAM) and definitions, and employ mechanistic biomarkers to characterize causal pathways and guide evidence-based strategies to protect this vulnerable, growing surgical population.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-58/rc

Peer Review File: Available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-58/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-58/coif). C.K.N. is a scientific consultant for Surgical Safety Technologies, Inc., which has created the OR Black Box technology used in Stanford Hospital. J.D.F. reported unrestricted research funding from Varian and Pacira for an investigator-initiated trial; funding from Eclipse Regenysis for an industry-sponsored clinical trial; consultant, stock, and patents for Costa Surgical Inc.; and Authorship Royalty Fees from UpToDate, Inc. and Merck. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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