The main objective of this study was to determine whether there is a difference between plasma levels of SP-D and CC16 in patients undergoing neurosurgery in the sitting position compared with patients operated on in the supine position. We found that the mean concentrations of SP-D and CC16 were similar in both groups. It is well recognised that the intraoperative sitting position is a situation that can result in iatrogenic penetration of air into the venous system and pulmonary circulation. Even in situations when a large air embolism was not diagnosed intraoperatively, a gradual permeation of air microbubbles can obstruct blood flow in distal capillaries. Reduced blood flow causes tissue ischaemia, and the microbubbles initiate an immediate inflammatory response and complement activation. VAE incidents have been detected by transesophageal echocardiography (TEE) in 76% of patients undergoing surgery in the sitting position
. It is therefore reasonable to assume that air microbubbles are present to a certain extent in the vast majority of cases. The lung injury and endothelial dysfunction that air bubbles cause have been confirmed in animal studies
, although in one study that used electron microscopy no physical damage to the endothelium could be visualised
, Endothelial cells normally have tight connections to prevent leakage of fluids into the surrounding tissues. Air bubbles in the microcirculation cause pressure on endothelial cells and increase the pore radius.
The appearance of gaps between endothelial cells in leakage of fluid and consequently interstitial pulmonary oedema
. In our study we did not confirm potential lung injury based on the increased levels of pulmonary proteins in the systemic circulation. Furthermore, we did not observe any differences in the duration of postoperative hospitalisation or the incidence of clinical symptoms or signs between the groups.
A small amount of SP-D can be detected in the blood of healthy individuals; the exact quantity is genetically determined and varies between individuals. Plasma levels of these proteins can be elevated in patients with a wide variety of diseases and after exposure to toxins. Determann and colleagues observed SP-D levels of 140 ng/mL in patients without lung injury, which almost doubled toh acute lung injury / acute respiratory distress syndrome (ALI/ARDS)
. However, a different study found the mean value of SP-D to be 88 ng/mL ( range 1–1354 ng/mL) in patients with lung injury.
 In healthy adults and children the average level of SP-D is approximately 60 ng/mL.
 Increased levels of SP-D have been reported in idiopathic pulmonary fibrosis (IFP), tuberculosis, pulmonary alveolar proteinosis, andlues vave ranger between 100 ng/mL (sarcoidosis) to 339 ng/mL (IPF) compared to a control group of healthy patients (66ng/mL). However, SP-D levels do not appear to be elevated in asthma, bacterial pneumonia, emphysema, bronchitis or bronchiectasis
[10, 22]. In our study, the SP-D level in healthy, mechanically ventilated patients during craniotomy without prior lung injury was 100 ng/mL. Mechanical ventilation can lead to lung damage, in an animal model the consequences of ventilator-associated lung injury (VALI) are increased pulmonary capillary permeability and pulmonary oedema, cellular damage and necrosis and diffuse alveolar damage. The factors affecting the development of VALI are positive end expiratory pressure (PEEP), the respiratory rate, pulmonary artery pressure, the arterial partial pressure of CO2, beta-adrenergic agonists and body position
. Determann and colleagues. studied the effect of ventilation on the levels ofSP-A, SP-D and CC16 and found that levels did not differ in patients mechanically ventilated with low tidal volumes and PEEP compared with a conventional ventilation technique in participants undergoing surgery in the supine position
. In contrast, lung damage is significantly lower in patients ventilated in the prone position compared with supine patients.
 Similarly, the sitting position appears to improve ventilation parameters
. However, these observations were made in patients who were not a risk of VAE.
The plasma CC16 concentration depends on factors such as lipid levels, body mass index, gender and smoking status, and changes can be observed in various lung diseases and after exposure to toxins. A decrease in the CC16 concentration was reported, for example, in smokers, while in patients with interstitial lung diseases an increase has been observed
[27, 28]. The plasma concentration of CC16 in healthy subjects was determined to be between 11.8 and 27.9 ng/mL
[29, 30]. CC16 is a small molecule (16 kDa) and its presence in the blood is a sensitive marker of alveolar damage
. However, in our study CC16 concentrations were similar in both groups.
Air embolism was diagnosed in 12.5% of cases. The incidence of intraoperative diagnosis of VAE is dependent on the method of detection. The more sensitive the method is the higher the incidence of VAE
. We diagnosed VAE on the basis of a sudden fall of >2 mmHg in end tidal CO2 (etCO2) and confirmation of the presence of air in blood drawn from the central venous catheter. This method is capable of detecting large embolisms, which can lead to lung injury. In our study, potential lung damage was not confirmed on the basis the changes detected in our chosen biomarkers. VAE is a dynamic condition in which embolic air diffuses across the alveolar capillaries and can thus be expelled in approximately 30 minutes
. Short-term resistance to flow in the pulmonary capillaries does not necessarily activate the inflammatory cascades that lead to a complex mechanism that results in the contact of air bubbles with the endothelium, leading to interstitial pulmonary oedema and then ALI/ARDS.
There were also no apparent clinical consequences of lung damage in patients operated in the sitting position, as the duration of hospital stay after surgery was not prolonged.
One limitation of our study is that we only took a blood sample once after surgery. Sampling within four hours of placing the patients in the sitting position could have missed later significant lung damage and thus a later peak of blood biomarkers. More frequent sampling could have revealed the time course of changes in biomarkers rather than providing a snapshot. Another limitation may be our choice of biomarkers and the fact that differences may have been observed if other proteins or cell-specific markers of acute lung injury and acute inflammation had been measured.