Background

Meningioma is the most common primary brain tumor, accounting for about 30% of central nervous system (CNS) tumors in adults [1]. For tumors that are growing or causing symptomatology, maximal surgical resection under general anaesthesia with intubation remains the standard of care for therapeutic management of meningioma [2]. The particularity of neurosurgery is that an altered state of consciousness impairs the respiratory, which in turn may reduce brain functions [3]. Thus, the incidence of postoperative pneumonia (POP) is high after craniotomy.

POP, one of the most common postoperative pulmonary complications (PPCs) after surgery, not only prolongs the hospital stay, but even increases the risk of other severe complications and postoperative mortality [4, 5]. Previous studies have shown that early extubation is associated with reduced PPCs and hospital stay after major surgery, but they mostly compared the prognosis of patients with extubation in the intensive care unit (ICU) and those patients with extubation in operating room [6,7,8,9,10,11]. To date, there are no studies regarding the optimal timing of extubation of ventilated patients after craniotomy in the operating room. And few studies explored the relationship between extubation time and POP in the neurosurgery subgroup. But it’s worth noting that the control of extubation time in the operative room is more clinically instructive for anesthesiologists. And early recovery of patients’ breathing and consciousness is conducive to neurosurgeons’ neurological evaluation. Thus, we aimed to explore the association between extubation time and POP after meningioma resection in the operation room and provided it for clinical practice as a reference.

Methods

This retrospective study was approved by the Institutional Review Board of the First Affiliated Hospital of Nan**g Medical University (IRB: 2021-SR-047), and the requirement for written informed consent was waived by the institutional review board. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies was referenced when we performed this study. All experimental procedures were performed in accordance with relevant guidelines and regulations (declarations of Helsinki).

Patient population

We determined the sample size from a similar study of previous non-cardiac surgery [6, 11,12,13]. And we retrospectively analyzed 820 patients who underwent meningioma resection at the First Affiliated Hospital of Nan**g Medical University from January 2016 to December 2020. We included patients aged >18y with the American Society of Anesthesiologists (ASA) physical status I-III. The exclusion criteria were as follows: (1) severe cardiac /lung /liver or renal insufficiency (The definition is in the Additional file 1. eTable 1); (2) preoperative lung infection or other organ infections; (3) incomplete clinical information; (4) emergency; (5) failure to reach extubation criteria in the operating room after surgery. In addition, to reduce unnecessary medical expenses, patients undergoing elective meningioma surgery in our hospital were usually extubated in the operative room, so we excluded the patients who unplanned admission to ICU.

Data collection

Data were obtained from the Hospital Information System, which could be listed as follows: (1) preoperative-related variables including sex, age (>18y), body mass index (BMI), preoperative co-morbidities (hypertension, diabetes, coronary heart disease (CAD), history of smoking, history of epilepsy, history of tumor, previous meningioma resection surgery, tumor size (maximum diameter), the World Health Organization (WHO) class of meningioma (I-IV); (2) intraoperative-related variables including ASA status (I-III), surgery duration, total volume of input fluid, total volume of blood loss, tracheal extubation time, time of post-anesthesia care unit (PACU) stay; (3) postoperative-related variables including ICU admission (yes/no), time of ICU stay, postoperative complications (POP, intracranial infection, coma, brain edema, intracranial hematoma, deep venous thrombosis (DVT)), post-surgical hospital stay, readmission rate. Among them, extubation time was defined as the time (in minutes) from the end of surgery to the time of extubation in the operating room.

Endpoints, exposures, and confounders

The primary outcome of this retrospective analysis was the incidence of POP, defined as a respiratory infection requiring antibiotic treatment and meeting at least one of the following criteria: new or changed sputum, new or changed lung opacities on a clinically indicated chest radiograph, temperature > 38.3 °C, leucocyte count > 12,000 μL− 1 [14, 15].

The primary exposure factor in our study was tracheal extubation time which is defined as the end of surgery to the removal of a tracheal tube. The decision regarding tracheal extubation time comprised a response to verbal commands, a positive gag reflex, tidal volumes > 6 mL/kg, respiratory rate < 20 times/min, oxygen saturation > 96% while breathing spontaneously (FiO2 ≤ 50%), normocarbia judged by end-tidal carbon dioxide, reversal of neuromuscular blockade judged by peripheral nerve stimulator or clinical assessment, core body temperature between 36.5 °C and 37.5 °C, and hemodynamics was stable without the support of vasoactive drugs.

After considering previous definitions of delayed awakening (20 min, 30 min) [16, 2 in the supplement). The maximum area under the curve increased when patients were divided into early or delayed extubation groups using 35 minutes. Delayed extubation was therefore defined as extubation occurring more than 35 minutes after surgery. Also, patients who developed POP showed a longer extubation time than that of patients without POP (41.6 ± 25.8 vs 31.5 ± 19.4 min, P <  0.001) (Supplementary Fig. 2).

Fig. 2
figure 2

Associations between extubation time and POP. Adjusted for age, gender, BMI, ASA score, surgery duration, history of smoking, size of tumor and WHO score

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Table 3 showed ORs and 95% CIs for risk of incident POP. In the crude model, there was a 1.40-fold increased risk of POP compared to a shorter extubation time cohort (< 35 min) (OR: 2.40, 1.34 to 4.31, P = 0.003). In multivariable logistic regression analyses, after adjusting for age, gender and BMI, the OR represented 2.24 (1.22 ~ 4.09). After adjustment for intraoperative and preoperative relevant covariates, we observed that the ORs of delayed extubation cohort (≥ 35 min) were consistently significant in all four models (2.60 (1.32 ~ 5.11), 2.46 (1.31 ~ 4.62), respectively). After adjustment for all covariates in table 2, the risk was increased by 1.73 times in the incidence of POP in the delayed extubation cohort (≥ 35 min) compared to shorter extubation time cohort (< 35 min). (OR:2.73, 1.36 to 5.47, P = 0.005). In PSM analysis, with matching age, gender, BMI, hypertension, diabetes, CAD, history of smoking, previous meningioma resection surgery, tumor size and WHO classification, the risk was increased by 1.81 times in the incidence of POP in the delayed extubation cohort (≥ 35 min) compared to shorter extubation time cohort (< 35 min) (OR: 2.81, 1.42 to 5.56, P = 0.003). After PSM adjustment, the association remained significant and was not affected by potential confounders (OR: 2.54, 1.16 to 5.53, P = 0.019).

Table 3 Associations between extubation time and POP in the crude analysis, multivariable analysis, and propensity-score analyses
Full size table

Discussion

Our data demonstrated that extubation time was associated with POP, in addition to well-known prognostic factors such as age, ASA score, history of CAD, WHO score, surgery duration and anaesthesia duration. Interestingly, anesthesiologists wait longer to extubate the elderly and patients who require a higher fluid infusion. While it was not surprising that patients with delayed extubation had a worse outcome, we discovered that early extubation within 35 minutes in the operating room, rather than in the ICU, had an independent effect.

Consistent with our results, previous studies have shown that early extubation is associated with reduced PPCs and shorter hospital stay after major surgery, but few have focused on the neurosurgical subgroup [6,7,8,9,10,11]. However, early recovery of patients’ breathing and consciousness is conducive to neurosurgeons’ neurological evaluation, especially in the “rapid awaking strategy” [3]. Our study extended these findings to explore a safe and optimal extubation time in neurosurgical patients.

Fandler-Höfler S et al. conducted a retrospective cohort study in the neurointensive care unit or stroke unit stay (n = 447) and described longer ventilation time was associated with a higher rate of pneumonia during neurointensive care unit or stroke unit stay (early (< 6 h)/ delayed (6 ~ 24 h)/ late (> 24 h) extubation: 9.6%/20.6%/27.7%, P <  0.01) [11]. In Nikoubashman O′ cohort, prolonged ventilation (> 24 h) was associated with POP during hospitalization and unfavorable functional outcome and death at follow-up (P ≤ 0.001) [10]. Different from previous studies, our design setting focused on the patients met immediate extubation criteria within the operating room. Interestingly, the same phenomenon also can be found in our study, delayed extubation (> 35 min in the operation room) was significantly associated with POP in patients after meningioma resection.

The reasons underlying the association between intubation duration and POP may be relative to pulmonary dysfunction. On the one hand, the particularity of neurosurgery is that lung dysfunction can be caused by damage to functional brain areas, neurological paralysis, or enteral malnutrition, et al. [20], which in turn may reduce brain function [3]. General anaesthesia with intubation, on the other hand, disrupts physiological lung function due to changes in chest wall mechanics and diaphragm relaxation, causing atelectasis, gas exchange disruption, and ventilation-perfusion mismatch [21]. Additionally, barotrauma, volutrauma, atelectotrauma, and biotrauma are partly responsible for ventilator-induced lung injury [22].

It is noteworthy that patients with delayed extubation had more intraoperative fluid infusion, so the reason of delayed extubation may be related to pulmonary and cerebral edema, especially in patients with massive blood loss [20, 23]. Considering the administration of diuretics and the risk of bleeding during major neurosurgery, anesthesiologists need to balance the basic fluid requirement. Because fluid overload could result in pulmonary edema, cerebral edema or acute kidney injury. Careful selection of the type of infusion fluid (crystalloid or colloid therapy), and the use of goal-directed fluid therapy (GDFT) may help to manage fluid balance in neurosurgical patients who are dehydrated due to administration of diuretics [24,25,26]. Controlling fluid balance to avoid pulmonary and cerebral edema may allow patients to be extubated sooner after surgery.

Patients in the delayed extubation cohort were older than those in the cohort with a shorter extubation time. Our result was akin to many other findings. Most of the previous research had examined that older age could be the independent factor for delayed extubation, which was in turn associated with worse outcomes [27, 28]. Elderly patients have increased sensitivity toward general anesthetics, and slow return of consciousness due to progressive decline in CNS function [29]. Not to mention, craniotomy itself can cause CNS dysfunction [20]. But with the progress of medical technology and increasing human life expectancy, an increasing number of meningiomas has been identified in elderly patient. Thus, anesthesiologists need to weigh against benefits of early extubation in elderly patients.

The limitation of this study is that it was a single-center, retrospective study. We collected as many sample sizes as possible, and rigorous data analysis was performed to demonstrate the relationship between airway extubation time and POP. Furthermore, the incidence of these complications depends largely on the difficulty of treatment. Easily accessible meningiomas are far more different from complicated skull-base ones. The former shared more limited incisions, shorter surgery time duration, as well as fewer blood transfusions [19, 20]. And the post-operative intensive care of skull-base meningiomas resection may be reserved for intubation and mechanical ventilation, resulting in a significant increase in POP. For this reason, we excluded patients who entered the ICU after surgery. The highlight of our study lies in the inclusion of patients who could be extubated in the operating room and met the extubation criteria, providing a reference for anesthesiologists working in the operating room.

Conclusion

In conclusion, delayed extubation after meningioma resection is associated with increased pneumonia incidence. Thus, appropriate patients should be extubated as early as possible in the operating room to decrease the incidence of POP. By doing so, it may help to reduce the use of ICU and specialized staff without altering other clinical postoperative complications and hospital length of stay.