Predictors of Prolonged Mechanical Ventilation Among Patients with Aneurysmal Subarachnoid Hemorrhage After Microsurgical Clipping

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency that occurs in 9–10/100,000 persons per year [1, 2]. Despite advances in neurocritical care, the mortality and morbidity rates of aSAH remain high, accounting for 2–5% of strokes [3‐5]. Survivors frequently have long-term disabilities. Age, aneurysm size, Fisher grade, Hunt and Hess grade, World Federation of Neurosurgeons (WFNS) grade, presence of intracerebral hemorrhage (ICH), and Glasgow Coma Scale (GCS) have been found to influence aSAH outcomes [6‐9]. Microsurgical clipping and endovascular therapy with coiling are the main treatment modalities for ruptured aneurysms. In such situations, generalized anesthesia with mechanical ventilation (MV) is required. In addition, patients are usually intubated endotracheally with MV for respiratory failure, airway protection, or altered mental status. Delayed cerebral ischemia is a common and detrimental complication after aSAH, which results in secondary brain injury [2, 10‐12].

Patients with severe brain injury may have longer durations of MV use and poorer outcomes than the general population of intensive care unit (ICU) patients [13, 14]. Specific recommendations regarding weaning from MV for the patient population with aSAH are still lacking. In addition, the risk of ventilator-associated pneumonia (VAP) is increased by delayed extubation despite meeting the readiness criteria [14]. Other significant complications of prolonged MV, including airway injury, ventilator-associated lung injury, and prolonged immobility, incur significant social and economic burdens [15, 16]. Predictive models of prolonged MV in aSAH patients after microsurgical clipping can provide useful information to facilitate the management of these patients in the ICU and help patient families and caregivers to better anticipate the treatment course and decision-making. However, only a few studies have analyzed the risk factors for prolonged intubation in these patients. Thus, this study aimed to determine the predictors of prolonged MV in aSAH patients who underwent surgical clipping. We hypothesize that aSAH patients with higher disease severity and comorbidities need prolonged MV after surgery.

Despite the importance of predictors of prolonged MV in facilitating the management of patients with aSAH, there are only a limited number of studies analyzing the risk factors for prolonged intubation in these patients. In this study we found that DM and Hunt and Hess grades were significantly associated with prolonged MV. To the best of our knowledge, this is the first study to provide a comprehensive characterization and analysis of the predictors of prolonged MV in patients who underwent microsurgical clipping to secure cerebral aneurysms (CAs) after aSAH.

Only patients who underwent clipping surgery after aSAH were included in the analysis. We focused on the unique considerations relating to airway management and analyzed prolonged MV in the aSAH population after microsurgery. Considering the deficits in neurological functions and changes in consciousness after aSAH, these patients may be weaned off MV when they pass the screen of weaning parameters. However, they may need re-intubation or continue to require an artificial airway. Based on the weaning parameters for the general critical care patients (PiMax − 30 cmH₂O, PeMax 30 cmH₂O, RSBI < 105, RR < 30 breaths/min, VE < 10 L/min, and VT > 5 mL/kg), 79 (73.1%) patients were extubated after passing the SBT; however, three (3.8%) of these patients were re-intubated within 72 h.

Management guidelines for CAs have been developing continuously since the 1990s [18‐20]. CAs are treated either surgically or endovascularly, and treatment decisions should consider the location and morphology of the aneurysms, comorbidities, or the need for emergency surgical hematoma evacuation. Critically ill patients on prolonged MV have significantly higher morbidity and mortality, and tracheostomy should be indicated [21]. Compared with prolonged use of a translaryngeal tube, a tracheostomy with decreased airway resistance can better accelerate the weaning process and the rate of success, improve patient comfort, and decrease in-hospital mortality and the duration of hospitalization [22, 23].

However, a limited number of studies have analyzed the risk factors for tracheostomy and prolonged intubation in patients with aSAH. In ICH, other risk factors for prolonged intubation include hematoma location, hydrocephalus, chronic obstructive pulmonary disease, and obesity [24‐26]. Unlike other forms of stroke, DCI and increased intracranial pressure from hydrocephalus should be considered during the treatment course after the ruptured aneurysm has been secured. Neurogenic pulmonary edema and respiratory distress syndrome occur in 20–23% [26‐28] and 18–50% [29‐31] of aSAH patients, respectively. In a study of 146 patients with poor-grade aSAH, Gessler et al. demonstrated that tracheostomy within 1 week was associated with a lower possibility of pneumonia and shorter MV but did not affect ICU length of stay, neurological function, or mortality [32].

The results of another study showed that a later tracheostomy in poor-grade aSAH patients was associated with longer hospitalization, venous thromboembolic events, and pneumonia [33]. Also, in a study comparing 1069 patients who underwent endovascular approach and 519 patients who underwent surgical approach after aSAH, rates of MV, pneumonia, deep vein thrombosis, and tracheostomy were higher in patients treated surgically [34]. Of the patients in these two treatment groups, 27.6% and 42.4% underwent MV > 4 days, and 19% and 32.4% patients underwent tracheostomy after prolonged MV, respectively [34]. The reasons for the disadvantage of craniotomy over the endovascular approach remain unclear, and further research is needed to understand the surgery-related physiological changes to discover the specific patient group requiring a tailored treatment.

In general, intubation is indicated in aSAH patients with GCS ≤ 8, elevated intracranial pressure, status epilepticus, elective surgical intervention, poor oxygenation or hypoventilation, hemodynamic instability, and a need for therapeutic hyperventilation or demand for heavy sedation [35, 36]. Furthermore, weaning off MV is a crucial process in these patients when the ruptured aneurysms are secured from rebleeding, their cardiovascular condition stabilizes, and they do not deteriorate neurologically and have an adequate gas exchange. Patients requiring prolonged MV are prone to skeletal muscle atrophy due to limited physical activity, respiratory muscle weakness, and many other complications, which can be improved by early weaning and physical rehabilitation [15, 16, 37].

Patients are first assessed for their readiness to wean based on satisfactory weaning parameters and an SBT, followed by the decision regarding possible extubation [38, 39]. Weaning parameters are used to evaluate respiratory physiology capacity and the ability to breathe adequately without assistance. The commonly used weaning parameters include PiMax, PeMax, VT, VE, RR, RSBI, airway resistance, and compliance [40, 41]. Compared to critically ill patients requiring MV due to other diseases, patients with aSAH and impaired consciousness may have a low respiratory drive and impaired coughing reflex to clear secretions and protect the airway, and these cannot be assessed by weaning parameters. Therefore, even if patients pass the weaning parameters, they may develop extubation failure and require re-intubation and MV for adequate airway protection and oxygenation [42, 43]. Additionally, these patients may benefit from continued endotracheal intubation to prevent aspiration and maintain the ability to suction secretions until the improvement of neurological functions.

The plasma glucose level at admission is an independent predictor of prognosis after myocardial infarction, coronary artery bypass graft surgery, and traumatic brain injuries, and in critically ill patients [44‐48]. In a study of 228 patients with endogenous diseases aged ≥ 75 years, DM was an independent predictor of extubation difficulty, including the use of MV > 14 days, re-intubation within 48 h after extubation, and tracheotomy [49]. In a meta-analysis of 39 studies involving 359,783 patients with ischemic and hemorrhagic stroke, DM was prevalent in 28% of the patients [50]. Most of the included studies found that DM was associated with higher mortality, poor functional outcomes, and longer hospital stays. In a retrospective study of 2540 aSAH patients, 9.4% of whom had DM, long-term MV was an independent predictor of poor functional outcome [34]. Patients with hyperglycemia have an approximately threefold increased risk for poor outcome after aSAH [51, 52]. In our study, 12% of the aSAH patients had a history of DM, which was a significant predictor of prolonged MV. The DCI usually occurs in 30–40% of aSAH patients, mostly between days 4 and 10, and it can progress to irreversible cerebral infarction with subsequent poor clinical outcomes [53‐55]. The authors of a systemic review concluded that there is an increased risk of DCI in patients with hyperglycemia (OR 3.2, 95% CI 1.8–5.8) and history of DM (pooled OR 6.7, 95% CI 1.7–26) [56]. DCI, which is the leading cause of secondary neurological deficits after aSAH, may be one of the factors associated with the pathophysiology of prolonged MV after aSAH.

Grading systems based on initial evaluation and imaging findings have been used to classify patients with aSAH. The most widely used grading systems are the Hunt and Hess grading system, Fisher grade, and the WFNS grading system. The Hunt-Hess and WFNS scales are the most widely used grading systems for clinical assessments in patients with aSAH. They primarily focus on the consciousness and neurological deficits that reflect the severity of brain injury [57]. In contrast, the modified Fisher scale is a commonly accepted radiological grading system that assesses the severity of brain injury by quantifying the amount and distribution of hemorrhage on computed tomography images to predict the incidence of vasospasm and DCI [58]. A higher Hunt and Hess grade implies a decreased level of consciousness and focal neurologic deficits, which may lead to impaired protective reflexes and an increased risk of aspiration.

A retrospective study of 669 aSAH patients compared the performances of different grading scores for predicting functional outcomes between patients who underwent microsurgical clipping and endovascular coiling. The results demonstrated that the clinical grading systems have significantly better predictive performance than the radiological grading systems in both groups [59]. These results are supported by other studies [60, 61]. A higher score on the WFNS scale, which uses the GCS and focal neurological deficits to grade the severity of aSAH, independently predicted prolonged intubation in patients with aSAH after surgical or endovascular treatment [62]. Rass et al. reported that a higher Hunt and Hess grade in aSAH patients was associated with an MV > 7 and 14 days [63]. Consistent with this, the current study found that a Hunt and Hess scale grade of 3–5 was an independent predictor of prolonged MV after clipping in aSAH patients. In contrast, modified Fisher grade (dichotomized to grade 1–2 and grade 3–4) was not significantly associated with prolonged MV in both the univariate and multivariate analyses. The WFNS scale score, as a clinical score, was significantly associated with MV in the univariate analysis but not in the multivariate analysis. These findings emphasize the importance of using different scoring systems for predicting different aspects of outcomes after aSAH.

As a common hospital-acquired infection after > 48 h of MV use, VAP is the leading cause of death from nosocomial infections in critically ill patients [64]. It is associated with prolonged hospitalization and increased healthcare costs, morbidity, and mortality [65, 66]. In patients on MV, the incidence of VAP increases with the duration of ventilation at approximately 1.5% per day [67]. With late tracheostomy or prolonged MV as a reference, early tracheostomy in patients requiring intensive care who are on MV at ≤ 7 days and ≤ 10 days after intubation have no significant benefits with respect to the length of ICU stay, hospital stay, duration of MV use, or survival [68‐70]. Further, it is important to predict the possibility of prolonged MV in neurocritical patients and determine the necessity and timing of tracheostomy. This can help patients benefit from tracheostomy and avoid unnecessary complications.

This study has some limitations. First, our data were collected retrospectively from a single institution. Thus, important confounders relevant to the results may have been missed. Therefore, future studies involving larger populations are needed to validate the generalizability of our results. Second, the patients were treated surgically by three neurosurgeons, and the postoperative treatment strategy may have varied. Third, not all patients had their blood sugar and glycated hemoglobin levels measured on arrival to the emergency room, which limited further detailed analysis of diabetic patients. Despite these limitations, this study remains valuable as it investigates an important aspect of MV use in a selected patient cohort and provides baseline evidence for further studies to improve the outcomes of aSAH patients.

In conclusion, a history of DM and Hunt and Hess grade 3–5 independently predict prolonged MV after microsurgical clipping in patients with aSAH. This finding may help to improve current weaning protocols and provide useful information to help both clinicians and families in better clinical decision-making.