Risk factors of delayed extubation after esophagectomy in the surgical intensive care unit

Introduction

Esophageal cancer is among the top 10 most prevalent cancers and is one of the leading causes of death related to gastrointestinal tumors (1), with the average 5-year survival rate of patients with this disease being approximately 20% (2). Esophageal cancer is a common malignant tumor of digestive tract, for which esophagectomy is the primary treatment. However, it is a high-risk surgical procedure characterized by grade IV complexity, necessitating intensive perioperative care. Patients undergoing esophagectomy are at heightened risk for respiratory complications, underscoring the critical nature of postoperative management in this population. Compared with other gastrointestinal surgeries, esophagectomy is more commonly associated with a higher incidence rate of postoperative complications and mortality (3,4). Tracheal extubation is a critical step during a patient’s emergence from general anesthesia. Certain features of esophagectomy for esophageal cancer, including the intraoperative duration of one-lung ventilation, postoperative elevation of inflammatory factors, and incisional chest wall pain, may decrease the likelihood of success for postoperative extubation (5). Inappropriate timing for extubation after esophagectomy may result in serious complications, such as acute respiratory failure, necessitating the use of noninvasive ventilation or reintubation followed by mechanical ventilation (MV); moreover, an overly delayed extubation may increase the risk of ventilator-associated pneumonia (VAP) and airway damage. Extubation-related adverse events (AEs) may prolong the hospital stay of patients and increase the medical burden (6,7). The primary aim of extubation is to reestablish the patient’s ability to breathe independently and to trigger an effective cough reflex, thereby freeing the patients from a reliance on MV and ensuring a smooth transition to normal respiratory function. However, the patient’s respiratory system may be in a relatively fragile state during the process of extubation. Residual effects of anesthesia, inflammation from surgical trauma, postoperative pain, and any pre-existing medical conditions may all increase the risk of adverse respiratory events after extubation. These complications may include hypoxemia, hypercapnia, respiratory obstruction, laryngospasm, aspiration, respiratory distress, and the need for reintubation (8).

Postoperative extubation requires careful monitoring of various parameters in the surgical intensive care unit (SICU). Delayed extubation after esophagectomy is caused by a combination of factors, which can be categorized as patient-related factors, surgery-related factors, and anesthesia management factors. Understanding these risk factors can aid in the identification of high-risk patients and facilitate targeted preventive measures. Several studies have focused on the incidence and risk of delayed extubation following spinal surgery and cardiac surgery (6,9), but delayed extubation after esophagectomy in the SICU has not been extensively examined.

We thus conducted this study to identify incidence and the risk factors of delayed extubation after esophagectomy in the SICU. Our findings may aid critical care physicians in predicting delayed extubation and preventing AEs. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-890/rc).

Methods

Patients

A single-center, observational study was conducted in which patients with esophageal cancer who were admitted after esophagectomy to the SICU in Renji Hospital (South Campus), School of Medicine, Shanghai Jiao Tong University, from July 2023 to December 2023 were enrolled. The inclusion criteria were as follows: (I) patients with esophageal cancer and over 18 years of age; (II) completion of transthoracic esophagectomy; and (III) resuscitation and extubation scheduled to be performed after admission to the SICU. Meanwhile, the exclusion criteria were (I) minimally invasive esophagectomy and (II) extubation occurring in the operating room. This study was approved by the Ethics Committee of Shanghai Jiao Tong University, School of Medicine, Renji Hospital (approval No. LY2022-045B), and its protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR2300068501). Informed consent was obtained from all participants or their guardians. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Data collection

Demographic characteristics, preoperative variables, intraoperative parameters, and postoperative variables were collected. Preoperative variables included comorbid conditions, pulmonary function tests, and laboratory examinations. Intraoperative parameters included American Society of Anesthesiologists (ASA) physical status, anesthesia and operative duration, urine volume, vasopressor agent use, and fluid management such as volume of intravenous crystalloids and colloids. Postoperative variables included mean arterial pressure (MAP), time of discontinuation of sedation and analgesia, time of resuscitation (time of from sedation cessation to a recovery of consciousness), time from spontaneous breathing trials (SBTs), and laboratory tests. Postoperative AEs were recorded. SICU length of stay (LOS), hospital LOS, and hospitalization costs were also recorded.

Extubation-related definitions

The indications of extubation included normal respiratory function [such as spontaneous respiratory rate, tidal volume (V_T), and other indicators met the requirements], complete recovery from neuromuscular block (including signs such as clarity of consciousness, good cough reflex and swallowing reflex, limb movement), and normal blood gas analysis results (10).

Extubation duration was defined as the time from the discontinuation of anesthetic medication to the immediate removal of endotracheal intubation. The expected time was within 90 minutes, a period which included the emergence from discontinuation of sedative and analgesic medications (60 minutes) and the success on SBT (30 minutes) (11,12). Patients extubated within 90 minutes were assigned to the early-extubation group.

Delayed extubation was defined as the endotracheal tube being removed after the conventional extubation time (>90 minutes) (11,12). Patients extubated after 90 minutes were assigned to the delayed-extubation group.

Extubation-related early AEs included reintubation within 48 hours and sequential noninvasive ventilation after extubation.

Statistical analysis

The data are presented as either a percentage, the mean ± standard deviation (SD), or as the median and the 25% to 75% interquartile range (IQR), as appropriate. The Chi-squared test was used to compare categorical data, while the Student t-test was used to compare continuous data. The Kolmogorov-Smirnov test was performed to assess the normality of data distribution. In cases in which the data did not follow a normal distribution, the Mann-Whitney test was used. We constructed a logistic regression model incorporating demographic variables and the factors with a univariate P value of <0.05. Stepwise logistic regression analysis was conducted to identify risk factors, with a P value <0.05 being considered statistically significant. Interrater reliability was determined according to the kappa value (>0.80) to ensure data consistency in data collection. SPSS 20.0 (IBM Corp., Armonk, NY, USA) was used for all statistical analyses.

Results

Total of the 172 patients with esophagectomy were screened. Of these, 53 met our exclusion criteria, including patients who underwent minimally invasive esophagectomy (n=51), extubation in the operating room (n=1), or total laryngectomy + tracheotomy + esophagectomy (n=1). The other two patients were excluded due to a lack of clinical data (Figure 1).

Figure 1 Flowchart of participant inclusion. ICU, intensive care unit.

Of the 117 enrolled patients, 91 (77.8%) were males. The mean age was 67.7±8.79 years, and the mean body mass index (BMI) was 22.51±3.28 kg/m². Additionally, 29 (24.8%) patients had hypertension, 19 (16.2%) had diabetes mellitus, 5 (4.3%) had coronary heart disease, 38 (32.5%) experienced ventilation dysfunction, and 29 (24.8%) experienced diffusion dysfunction (Table 1).

Among all enrolled patients, 49 (41.9%) were placed in the delayed-extubation group, for which the median time from resuscitation to extubation was 140 (IQR, 120–197) minutes. The remaining patients were placed in the early-extubation group, for which the median time from resuscitation to extubation was 75 (IQR, 60–85) minutes. There was no significant difference in the demographic variables between the delayed- and early-extubation groups, nor were there any differences in comorbid conditions or BMI. The results of the pulmonary function test indicated that the proportion of ventilation dysfunction and diffusion dysfunction was higher in the delayed-extubation group than in the early-extubation group, but not significantly so (ventilation dysfunction: 38.8% vs. 27.9%, P=0.44; diffusion dysfunction: 30% vs. 20.9%, P=0.44). The groups had similar pulmonary function parameters, such as forced vital capacity (FVC)/forced expiratory volume in 1 second (FEV1) (measured values/predicted values%, pred%), maximal voluntary ventilation (MVV) (pred%), maximal expiratory flow (MEF) 50 (pred%), single-breath carbon monoxide diffusing capacity (DLCO-SB) (pred%), and DLCO-alveolar volume (VA) (pred%). Moreover, the two groups did not differ significantly in terms of preoperative laboratory examination findings, including white blood cell (WBC) count, neutrophil percentage, hemoglobin (Hb) level, hematocrit (HCT) level, platelet (PLT) count, prealbumin level, albumin level, and serum creatinine (sCr) level (Table 1).

Regarding the intraoperative variables, compared to those in the early-extubation group, patients in the delayed group had a longer operative duration (254.41±76.41 vs. 229.32±49.14 min; P=0.03), higher median colloid infusion volume {750 [interquartile range (IQR), 450–750] vs. 500 (IQR, 250–750) mL; P=0.01}, and a lower urine volume (1.79±0.9 and 2.36±1.41 mL/kg/h; P=0.01); however, crystalloid infusion, vasopressor agent use, and blood loss were not significantly different between the two groups. Additionally, there was no significant difference in terms of open approach, ASA status, time from discontinuation of neuromuscular blocking agent to admission to the SICU between the two groups. For intraoperative MV parameters, there was no significant difference in the two-lung ventilation V_T, one-lung ventilation V_T, or duration of one-lung ventilation between the two groups. Intraoperative lactate and glucose levels were also not significantly different (Table 1).

Five patients received high flow nasal cannula (HFNC) therapy sequentially after extubation in the delayed group, and only one patient received HFNC in the early group (10.2% vs. 1.5%; P=0.04). One patient in each group required reintubation within 48 hours (1.5% vs. 2%; P=0.81). A greater proportion of patients contracted hospital-acquired pneumonia (HAP) in the delayed group than in the early group (26.5% vs. 10.3%, P=0.02). However, there was no significant difference in anastomotic leak incidence between the two groups (16.3% vs. 7.4%; P=0.13) (Table 1).

Compared to that in the early group, the hospitalization expense in the delayed group was higher [10.74±3.15 vs. 9.8±1.46 (in CNY ¥10,000); P=0.04]. In the delayed group, 13 of the patients had a duration of antibiotic >7 days, representing a greater proportion than that in the early group (26.5% vs. 5.9%; P=0.002). There was no significant difference in ICU LOS, hospital LOS, or ICU cost between the two groups (Table 1).

In the multivariate logistic regression, intraoperative colloid infusion >500 mL was an independent risk factor for delayed extubation [odds ratio (OR) =2.97; 95% confidence interval (CI): 1.41–7.81; P=0.009], while a higher intraoperative urine volume was an independent protective factor for delayed extubation (OR =0.62; 95% CI: 0.39–0.88; P=0.03) (Table 2). The risk of delayed extubation was 2.97-fold higher in patients receiving intra-operative colloid infusion >500 mL compared to those receiving ≤500 mL. Additionally, for each 1 mL/kg/h increase in intra-operative urine volume, the risk of delayed extubation decreased by 38%.

Discussion

One of the principal findings of this study was a high incidence rate (41.9%) of delayed extubation in the SICU. The patients with delayed extubation had higher hospitalization costs than did those with early extubation. Intraoperative colloid infusion >500 mL and per 1 mL/kg/h increasing in intra-operative urine volume were independently associated with delayed extubation.

The timing of extubation after esophagectomy remains controversial, with no standard practices being established, even in experienced centers. Moreover, a universal definition for the time of delayed extubation remains lacking. Despite advances in intensive care medicine, there is no consensus regarding the optimal time for extubation. Several studies have reported that extubation within 6 hours after pediatric general anesthesia cardiac surgery results in a shorter LOS and fewer AEs (13); however, there are few studies on the extubation time after major adult general anesthesia surgery. Delayed emergence from anesthesia, defined as the failure to regain consciousness 30–60 minutes after discontinuation of general anesthesia, is not uncommon in grade IV surgery (11). We defined early extubation time as that within 90 minutes of discontinuation of anesthetic medication, inclusive of resuscitation and SBT time. According to this definition, the median time from emergence to extubation was 140 minutes in the delayed-extubation group and 75 minutes in the early-extubation group. This difference needs to be further clarified based on the actual clinical situation and research purpose.

Esophagectomy is a complex surgical procedure and requires careful postoperative management. Once patients enter into the SICU after surgery, they still require appropriate sedation and analgesia, dynamic monitoring of oxygenation, observation of thoracic drainage characteristics, calculation of real-time urine volume, and timely resuscitation and extubation. In our study, one of the extubation-related AEs was acute respiratory failure, requiring noninvasive ventilation (HFNC) or invasive ventilation (reintubation). We found that 10.2% of patients with delayed extubation required sequential HFNC, while only 1.5% of patients with early extubation required this measure. Early extubation can prevent postoperative pulmonary complications such as infection and respiratory failure (14).

Gal et al. found that delayed extubation after spine surgery was associated with a longer ICU and hospital LOS and a higher cost of hospitalization (6). In our study, patients with delayed extubation after esophagectomy endured higher hospitalizations costs but did not have a longer LOS. LOS may be related to perioperative management and other complications, and the relevant factors should be identified in further research.

Delayed extubation is more likely to occur in patients with fluid overload or poor pulmonary function. Intraoperative fluid management, as reflected by urine volume, can influence postoperative pulmonary and renal function, thereby affecting the likelihood of successful extubation (15). We found that patients with delayed extubation received a greater colloid infusion volume and had a lower urine volume during operation as compared to those with early extubation, which is in line with other work (16). Excessive fluid administration may lead to fluid overload, which may contribute to pulmonary complications and complicate extubation. Fluid overload may impair pulmonary function by increasing interstitial lung fluid, reducing lung compliance, and worsening oxygenation. In turn, this may delay extubation or increase the risk of extubation failure.

Intraoperative colloid infusion is primarily used to maintain blood volume and increase osmotic pressure. Although colloid infusion has been reported to reduce certain surgical complications (17), it may also increase the risk of acute kidney injury (18). For esophagectomy, the dosage and type of colloid application have not been characterized. Goal-directed fluid therapy (GDFT) represents an advancement in fluid management. Improper fluid management may increase the risk of AEs related to extubation, and it has been reported that GDFT can significantly reduce the incidence of postoperative pulmonary complications in patients undergoing esophagectomy (19). In our study, intraoperative colloid infusion >500 mL increased the risk of delayed extubation by 2.97 times. Studies with greater statistical power are needed to confirm the hypothesis that lower intraoperative colloid infusion volume can reduce the risk of delayed extubation.

Intraoperative urine volume is often used as a surrogate marker for renal perfusion and overall fluid balance during surgery. Adequate urine volume is generally associated with better renal function and fluid status (20). In this study, the mean intraoperative urine volume of patients with delayed extubation was 1.79±0.9 mL/kg/h, while that of patients with early extubation was 2.36±1.41 mL/kg/h. The optimal balance of intraoperative fluid administration and urine volume is crucial. Assessing dynamic parameters to guide fluid administration may help achieve this balance, yet further research is needed to establish the specific thresholds for urine volume and fluid administration in this context.

Research suggests that intraoperative positive fluid balance may lead to the occurrence of esophageal cancer-related postoperative pulmonary complications (21). Moreover, an excess of fluid does not increase urine volume, which may also heighten the risk of kidney injury due to increased return blood volume and venous pressure (22). Studies have shown that restrictive fluid strategies during esophagectomy may reduce postoperative complications, including pulmonary issues (23). A balanced approach to intraoperative fluid management is essential to facilitating successful postoperative extubation (24).

Other research indicates that preoperative pulmonary function is associated with postoperative extubation-related AEs (25). In our study, 38.8% and 30% of patients with delayed extubation had ventilation function dysfunction and diffusion dysfunction, respectively. Although there was no statistical significance between the early- and delayed-intubation groups, there was a higher proportion of patients with pulmonary dysfunction in the delayed group than in the early-extubation group. However, this finding needs to be confirmed in larger-sample studies.

Thoracoscopic minimally invasive surgery and classical open thoracoscopic surgery have their respective advantages. The former provides patients with a shorter hospital stay, less intraoperative blood transfusion, and lower risk of postoperative intestinal obstruction and incisional infection, yet it is associated with a longer operation time and a higher risk of reoperation and empyema (26). However, there remains a lack of large-sample, randomized controlled trials regarding this topic, and no studies comparing these two surgical approaches in terms of postoperative extubation AEs have been conducted. Espinoza-Mercado et al. analyzed data from the National Cancer Database from 2010 to 2015 and found that 28.4% of the 5,553 included patients underwent minimally invasive esophagectomy and that 7.8% underwent robotic-assisted minimally invasive esophagectomy (27). In our study, 51 (29.7%) patients who underwent thoracoscopic surgery patients were not included in the analysis. The AEs after extubation between minimally invasive surgery and classical surgery need to be further clarified in future research.

Certain some limitations to our study should be noted. First, we employed an observational, single-center design with a small sample size. A multicenter, prospective study with a larger sample size should be performed in the future. Second, there has been an increase in the use of dynamic multimodal hemodynamic monitoring for predicting postoperative complications, with the related parameters including dynamic urine flow rate measurement, stroke volume variation, and extravascular lung water, among others. In the future, these data may be used to build more effective models for predicting delayed extubation through machine learning, which may help reduce postoperative pulmonary-related complications. Third, the duration of our study was short, with the 6-month period potentially restricting sample diversity, and seasonal biases might have been introduced.

Conclusions

Delayed extubation after esophagectomy remains a common occurrence in the SICU and is an important factor contributing to the increased risk of AEs and medical costs. Intraoperative colloid infusion >500 mL and per 1 mL/kg/h increasing in intra-operative urine volume were associated with delayed extubation and thus should be carefully monitored during the perioperative period.

Acknowledgments

We thank Tianxing Xue for completing the data entry.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-890/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-890/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-890/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-890/coif). The 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. This study was approved by the Ethics Committee of Shanghai Jiao Tong University, School of Medicine, Renji Hospital (approval No. LY2022-045B). Informed consent was obtained from all participants or their guardians. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

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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