Postoperative Remote Lung Injury and Its Impact on Surgical Outcome

Lin Chen; Hailin Zhao; Azeem Alam; Emma Mi; Shiori Eguchi; Shanglong Yao; Daqing Ma


BMC Anesthesiol. 2019;19(30) 

In This Article

Therapeutic Strategies

In recent years there has been an increasing understanding of the possible pathophysiological processes underlying the development of postoperative remote lung injury, with evidence to suggest that it may be possible to exploit this knowledge to reduce its incidence within the clinical environment.

In vivo models of ARDS have demonstrated that various anaesthetic agents, including isoflurane, sevoflurane and desflurane, possess anti-inflammatory and cytoprotective effects.[71–73] These data suggest that volatile anaesthetic agents may possess significant protective effects in ameliorating ARDS as a result of a variety of pathogenic insults. Whilst there is limited clinical evidence specifically purporting the protective effects of these agents against postoperative remote lung injury, given the fact that the various insults studied share common pathogenic pathways with remote lung injury, it is reasonable to ascertain that these volatile anaesthetic agents may too be protective against remote lung injury.

Isoflurane is a commonly used volatile anaesthetic agent[74] and has been shown to possess both anti-inflammatory[75] and cytoprotective[76] properties. Animal models of lung injury, including mechanical ventilation induced lung injury and inhaled endotoxin,[71,77] have demonstrated the potential utility of isoflurane as a pulmonary protectant. Proposed mechanisms include the downregulation of NF-κB by reducing its expression and simultaneously upregulating I-κB expression, whilst also mediating the expression of apoptotic markers, including Bcl-2 and Bax,[78,79] as well as a reduction in vascular leak.[71] Furthermore, isoflurane also attenuated LPS-induced lung injury by inhibiting NLRP3 inflammasome activation.[80] The fact that isoflurane attenuates the activation of common inflammatory pathways suggests that the perioperative attenuation of these pro-inflammatory mediators in patients undergoing surgery may reduce the incidence of remote lung injury.

Sevoflurane, another commonly used inhaled anaesthetic agent, has similarly been demonstrated the ability to ameliorate lung injury in vivo. In animal models of lung injury, sevoflurane has consistently demonstrated its protective properties by reducing deleterious histological changes, reducing wet to dry ratio and improving ventilation parameters.[81–83] Furthermore, sevoflurane administration caused a reduction in neutrophil infiltration, pro-inflammatory cytokine release as well as a reduction in NF-κB expression.[84,85] The release of inflammatory cytokines has been shown to be involved in the pathogenesis of remote lung injury, once against suggesting that the use of sevoflurane may similarly reduce the incidence of remote pulmonary insults following surgery.

Propofol has been shown to reduce the expression of a similar cytokine profile to sevoflurane, thus conferring a 2-fold increase in survival in an LPS model of lung injury by reducing pulmonary oedema and histological damage via its anti-inflammatory and anti-oxidative properties.[86,87] Dexmedetomidine (Dex) is a sedative that has been demonstrated anti-inflammatory effects and the ability to ameliorate lung injury. Dex is a potent and highly selective α2-adrenergic agonist that exhibits sedative, analgesic, amnestic, and sympatholytic properties. Previous studies have demonstrated that Dex was able to protect against lung injury following kidney ischaemia-reperfusion injury due to its ant-inflammatory effects[88] and ability to reduce pulmonary microvascular hyper-permeability.[89] Furthermore, Dex reduced caspase 3 and Bax expression, whilst upregulated Bcl-2 expression. As animal studies have indicated the significant role of caspase 3 dependent lung epithelial cell apoptosis in the pathogenesis of remote lung injury,[42,43] including hepatopulmonary syndrome, Dex's anti-inflammatory effects may reduce the incidence of post-operative remote lung injury in clinical practice but warrant further study.

Another therapeutic approach may be the use of xenon, a novel general anaesthetic agent, that has demonstrated anti-inflammatory and anti-apoptotic effects in models of acute lung injury following renal injury.[90]

Furthermore, numerous observational studies have attributed the judicious use of intravenous fluid in the perioperative period with a higher incidence of acute lung injury.[91,92] One randomized clinical trial conducted by Volta CA et al. showed that patients received balanced solutions experienced lower concentration of active matrix metalloproteinase-9 and higher level of tissue inhibitor of metalloproteinase-1 and IL-10 compared to the unbalanced solutions.[93] Whilst a large RCT of patients with acute lung injury found that conservative administration of intravenous fluids is associated with an improvement in oxygenation, lung compliance and 60-day survival.[94] This is a potentially simple way of reducing the incidence of perioperative lung injury, however must be balanced with the risks associated with dehydration.