Our study investigated effects of intraoperative LPV on respiratory function and the incidences of postoperative complications in emergency TBI patients. The results demonstrated that intraoperative continuous administration of small VT + PEEP could improve oxygenation and respiratory mechanics parameters, decrease incidences of PPCs, and lower increase in posttraumatic serum levels of brain injury markers. However, implementing intermittent RMs might disturb intraoperative cerebral hemodynamics, leading to the fluctuation of ICP.
Small VT ventilation (6–8 mL/kg CBW) is now served as the respiratory care standard for ARDS patients in ICU. A consensus has been formed that it is also suitable for patients with healthy lungs in operating room [9, 10]. An animal experiment showed that small VT ventilation could more effectively promote the oxygenation of rats with brain injury than large VT ventilation [11]. Furthermore, large VT ventilation in TBI patients might be associated with the occurrence of ARDS, and its incidence increased to some extent with the VT [12]. However, a single use of small VT causes periodic alveolar collapse of local lung tissues, thus increasing the risk of atelectasis. Interestingly, this adverse effect can be offset by combining PEEP and/or RMs, which would inevitably involve positive pressure ventilation and might adversely affect ICP and CPP [13–15]. However, another study showed that high PEEP (5-15cmH2O) could improve PaO2 of local brain tissue without affecting ICP and CPP in patients with TBI and ARDS [16]. In summary, the interaction between the lung and the brain poses an important challenge to the ventilation management in TBI patients. An optimal ventilation strategy for TBI patients requires in-depth discussion.
In this study, two groups of TBI patients were treated with LPV: small VT (8 mL/kg CBW), intraoperative continuous administration of 5cmH2O PEEP. And some were given RMs before opening and after closing the endocranium. Our results showed that intraoperative application of small VT + PEEP or small VT + PEEP + RMs improved oxygenation and pulmonary compliance in TBI patients compared to those treated with conventional MV. However, no significant differences in PaO2 and Cdyn were found between two intervention groups, suggesting that RMs might not provide further improvement on the basis of PEEP. Ppeak, close to airway pressure, reflects the dynamic compliance of respiratory system. Recently, Pplat was recommended as a better predictor of barotrauma and VALI, which was closer to alveolar pressure and reflects the static compliance of respiratory system [17]. Our results showed that patients intervened with LPV had lower Ppeak and Pplat than those receiving conventional MV, suggesting that the implementation of LPV improved respiratory mechanics parameters, and contributed to relieve barotrauma and PPCs. However, there was a rise in PaCO2 at the end of surgery in patients receiving LPV, which may be explained by CO2 retention resulted from reduced periodic alveolar collapse and expansion following small VT. But the little rise could be considered as a compensatory state that would not cause obvious pathological damage [18]. The incidence of intraoperative hypoxemia was lower in two intervention groups, while the cardiovascular adverse reactions in small VT + PEEP + RMs group were more frequently observed. Since intrathoracic pressure increased rapidly in a short time, RMs-treated patients generated a decrease in blood volume returning to the heart, and the cardiac output [13]. Collectively, although small VT + PEEP + RMs can improve intraoperative oxygenation and respiratory mechanics parameters in TBI patients, RMs may cause adverse effects on hemodynamics, while small VT only combined with PEEP can improve lung function without affecting their circulatory stability.
Another primary outcome was the incidence of PPCs in three groups. PPCs are the most common mid-term complications after major surgery and strongly linked to clinical prognosis [19]. An observational study in 29 countries named LAS VEGAS showed that 80% severe TBI patients developed PPCs [20]. Serious pulmonary complications, like ARDS, NPE or VALI, are associated with high mortality, unfavorable neurological outcomes, longer ICU retention and hospital stays in TBI patients [21]. We investigated the incidence of pulmonary complications within postoperative 30 days. The incidences of hypoxemia, pulmonary infection, and atelectasis in LPV-intervened patients were significantly lower than those of patients receiving conventional MV, which was consistent with Marret E et al [22] study. Moreover, using LPV significantly reduced postoperative ventilation time, which might be attributed to the improvement of intraoperative respiratory function and decreased risk of PPCs by small VT combined with PEEP and RMs. The GOSE score is usually used to evaluate the degree of disability and neurological prognosis of TBI patients [23]. Our results showed no statistical differences in GOSE score among three groups after 30 days, probably owing to a short follow-up time and limited sample size. Postoperative neurological complications and hospital stays were comparable among three groups, possibly because improving ventilation strategy alone hardly achieved a breakthrough in neurological outcomes of TBI patients. Surgical factors, the quality of nursing, and family economical state, are all needed to be considered comprehensively.
The biggest concern about TBI patients with perioperative LPV is that it may have an adverse effect on ICP and CPP. Ultrasound measurement of ONSD is a novel non-invasive method, widely used to dynamically and rapidly assess changes in ICP. It has a close correlation with canonical direct intubation in ventricle to estimate intracranial hypertension [24, 25]. Our ultrasound results showed no significant changes in ONSD at any time both in conventional MV and small VT + PEEP group, suggesting that intraoperative continuous administration of 5cmH2O PEEP did not affect patients’ ICP. Mascia et al [26] randomly applied 5cmH2O or 10cmH2O PEEP in 12 patients along with brain injury and ARDS. They found that the PEEP level, which was insufficient to give rise to excessive alveolar expansion or an evident increase in PaCO2, had no significant impact on ICP, and could safely improve oxygenation. Likewise, if the PEEP value was lower than that of ICP during MV, the elevation of intrathoracic pressure within a certain range would not increase ICP [27]. Therefore, 5cmH2O PEEP was applied in our study not lifting ICP visibly, because it did not cause alveolar hyperinflation or it was less than patients' ICP. However, RMs could rapidly expand the alveoli in a short period and increase the pressure in the thoracic cavity, which blocked the return of systemic circulation to the right atrium (cerebral venous reflux) and eventually increased ICP. After ceasing RMs, the intrathoracic pressure dropped to normal, and patient's ICP decreased accordingly [28]. Consistent with previous finding [29], a single RM transiently increased ONSD, which returned to the baseline within 5–10 minutes, indicating that RMs had the risk of elevating ICP of TBI patients.
Immediately after acute brain injury, astrocytes undergo mechanical deformation or local necrosis, leading to increased serum concentration of GFAP [30–32]. UCHL1 is a neuron-specific cytosolic enzyme and its serum level in acute phase of cerebral injury strongly correlated with the severity of damage [33]. Combined testing of GFAP and UCHL1 could more accurately diagnose the severity of brain damage and predict the long-term prognosis [34]. Here, postoperative serum levels of GFAP and UCHL1 in each group were higher than before. Possibly because they were released from necrotic cells and accumulated with the posttraumatic time course [35]. Furthermore, both serum levels of GFAP and UCHL1 in Group B were lower than the others at T3. It is considered that PEEP can improve oxygenation, reduce the release of inflammatory mediators of the lung and brain, thereby alleviating secondary injuries. Interestingly, additional RMs posed a large continuous positive airway pressure in a short time, which had an adverse effect on cerebral hemodynamics that neutralized favorable results of implementing PEEP. Hence, intraoperative application of small VT + PEEP could prevent further brain damage in TBI patients to some extent. Whether RMs played the same role remained further exploration.
Several limitations in our study should be noteworthy. First, actual values and accurate changes in ICP were unable to be obtained from ultrasound measurement of ONSD. Second, our results may not be applicable to other neurosurgical patients, like intracranial tumors, craniocerebral injury in sitting position during operation, spontaneous cerebral hemorrhage, etc. Third, during the study period, especially before operation, some severe patients were treated with mannitol and dexamethasone due to their conditions, which might affect the results consequently. Fourth, a 30-day postoperative follow-up was unable to accurately evaluate long-term survival and life quality of TBI patients. Last, it was a single-center study with limited sample size. Large-scale clinical trials are needed in the future to validate the impact of intraoperative LPV on TBI patients.