Secondary analysis of preoperative predictors for acute postoperative exacerbation in interstitial lung disease – Scientific Reports

In this case-matched retrospective observational study, we found that OLV, intraoperative steroid administration, and high mean inspiratory pressure were potential predictors of postoperative AEs during general anesthesia in pulmonary and non-pulmonary surgeries. On the contrary, high intraoperative F_IO₂ levels were not revealed to be associated with postoperative AEs. Multiple logistic regression indicated a significant association between OLV and postoperative AEs.

The AEs occurred in patients who underwent OLV, even in non-pulmonary surgery. It has been suggested that OLV itself is a risk factor for the development of AEs. In addition to pulmonary surgery (14 cases), this study included one case of distal arch descending aorta replacement, one case of thoracoscopic thymectomy, and three cases of esophagectomy among the OLV cases in the AE group. These surgeries were performed without direct lung invasion. Therefore, further investigation is necessary to assess whether OLV is an independent risk factor for postoperative AEs in non-pulmonary surgeries.

During OLV, the ventilated lung may be exposed to greater stress due to the higher pressure compared to that in two lung ventilation. In the present study, the mean airway pressure in the AE group was 0.9 cmH₂O higher than that in the non-AE group, and the difference was statistically significant. Low tidal volume and high PEEP management are recommended treatment strategies for ARDS^15,16. Moreover, high airway pressure can cause ventilator-induced lung injury (VILI)¹⁷. In 2015, Amato et al. reported that low driving pressure (single ventilation, volume/compliance) is associated with increased survival in patients with ARDS¹⁸. The probability of postoperative complications has also been reported to increase by 3.4% for every 1 cmH₂O increase in driving pressure during OLV^19,20. Considering that the mean airway pressure difference between the AE and non-AE groups in this study was 0.9 cmH₂O, the effect of driving pressure could be related to AEs.

There was a significant difference in the average mean airway pressure in the AE group in the present study. Driving pressure is often considered an indicator of ventilation management¹³. However, we could not evaluate driving pressure because we could not extract data on tidal volume, respiratory system compliance, and plateau pressure from the anesthesia database. Therefore, it remains unclear whether high mean airway pressure affects the development of postoperative AEs.

Preoperative steroid use is reported to be a predictor of AE following pulmonary resection⁶. The results of the present study suggested that steroid use during general anesthesia may be a predictor of postoperative AE. In the present study, the purpose of steroid use was not limited to prophylaxis for AE (e.g., hydrocortisone for liver resection and methylprednisolone for cardiopulmonary bypass). Moreover, an association has been reported between high average daily steroid use for AE-IPF and in-hospital mortality²¹. Therefore, we should carefully assess perioperative steroid use in patients with ILD.

Several studies have suggested that high F_IO₂ levels may damage lung tissue^8,9,10. However, in the present study, there was no significant difference in F_IO₂ between the AE and non-AE groups. One possible reason for this is that the anesthesiologists in charge who are aware of the risk are expected to maintain inspiratory oxygen levels at the minimum necessary. It is unclear whether AEs occur more frequently when higher oxygen concentrations are administered.

There were no differences between the two groups in the use of volatile or intravenous anesthesia in the present study. We could not determine the anesthesia method that was more favorable in preventing respiratory complications in patients with ILD. More studies are needed to determine whether the choice of anesthesia for patients with ILD is associated with postoperative AEs.

The factors evaluated in the present study are those that anesthesiologists can observe or intervene to treat during the perioperative period. Higher peak pressure might be needed because of a “difficult to ventilate” lung, so that this would be an unmodifiable factor. However, since high airway pressure itself may be the cause of AEs, it is worthwhile to consider lung protective ventilation during surgery. In addition, since OLV may be avoided in pulmonary surgery²², it is worthwhile to consider the indication for OLV in patients who are at high risk. Furthermore, the findings of this study can be useful for anesthesiologists in determining perioperative strategies for ILD patients.

Limitations

Our study has some limitations. First, causality and the effect of unmeasured confounding factors could not be determined, as this was a retrospective study. Second, we were unable to extract the data of some parameters from the anesthesia database. Comparison of the tidal volume, respiratory system compliance, and plateau pressure between patients in the AE and non-AE groups would have facilitated clarification of whether AEs are due to OLV itself or ventilator management. Third, this was a single-center study. Therefore, a study on the management of general anesthesia in patients with ILD at multiple centers is needed.

Although case matching of pulmonary and non-pulmonary surgery requires a large number of cases, we did not perform this study because it was a secondary analysis, and the number of cases was limited. However, we thought it would be worthwhile to examine whether OLV itself contributes to the occurrence of AEs, regardless of whether pulmonary surgery is performed.

We recommend that clinical studies be carried out to determine clinical strategies for better AE management. In addition, a prospective study with a larger number of AEs should be conducted to compare the results.