We conducted a retrospective subgroup study that investigated the influence of not only the initial postoperative lactate level but also the duration of postoperative hyperlactatemia on RF in patients treated with definitive surgery for intestinal fistula. It was found that, in patients with an initial postoperative lactate level more than 4 mmol/L (groups B and C), the duration of hyperlactatemia was associated with RF; however, in patients with an initial postoperative lactate level less than 4 mmol/L, the duration of hyperlactatemia had no value in predicting RF.
In previous studies, the postoperative lactate level was associated with postoperative outcomes after gastrointestinal surgery. Ben C Creagh-Brown et al.14 investigated more than 100,000 people after gastrointestinal surgery, and they found that the postoperative peak lactate level within 24 hours was independently associated with in-hospital mortality and postoperative length of stay in the hospital. Shimazaki J et al.15 found that the postoperative lactate level was a mortality marker in patients with colorectal perforation. In addition to the initial postoperative or peak lactate level, researchers started to pay attention to the association between change in the postoperative lactate level and prognosis. Veličković J et al.10 investigated the change in the postoperative lactate level at the 4th, 12th, and 24th hour after abdominal surgery, and it was found that the lactate level at the 12th hour was the most valuable to predict the prognosis. Li et al.16 conducted a small prospective study and found that dynamic changes in blood lactate levels during the first 24 postoperative hours were significantly associated with complications after major elective abdominal surgery. In those previous studies the postoperative hyperlactemia within 24 hours might a response to the severity of the surgical trauma, which might be associated the postoperative outcomes. However, in our study,all the patients had severe surgical trauma. Maybe in this cases, the recovery was more important for RF. And the duration of postoperative hyperlactemia might be a reflect on the recovery.
The process of complicated definitive surgery for intestinal fistula seems to be an abdominal surgeon's nightmare. During the process, the anatomical structure is disordered, the adhesion is severe, and there is a large amount of extensive bleeding in the operation field7,8. The above factors cause severe postoperative stress in the patients; thus, leading to release of cytokines and inflammatory mediators (including tumor necrosis factor alpha (TNF-α), and several interleukins (IL-1, IL-6, and IL-8))17. Along with the upregulation of proinflammatory cytokines and acute phase proteins in response to surgical stress, there is activation of the hypothalamic-pituitary-adrenal axis that leads to endocrine and metabolic disorders18. In addition, the increased inflammatory response following surgery leads to the suppression of mitochondrial activity and damage of mitochondria18. Moreover, the release of inflammatory factors can damage endothelial cells and aggravate microcirculatory disturbance19. These pathological processes lead to tissue hypoxia and ischemia 11. Direct manifestation of postoperative hyperlactatemia is tissue hypoxia. Adequate oxygen supplementation is critical for nearly all wound healing processes. It prevents wounds from infection; induces angiogenesis; increases keratinocyte differentiation, migration, and re-epithelialization; enhances fibroblast proliferation and collagen synthesis; and promotes wound contraction20, 21. In addition, the level of reactive oxygen species (ROS) is critically dependent on the oxygen levels, which is thought to act as cellular messengers to stimulate key processes associated with wound healing22. As an important index, the duration of hyperlactatemia has an obvious effect on tissue healing and prediction of RF.
In addition, it is well known that the first 48 hours after injury is the crucial period for neutrophils to enter the injured area through capillaries. During this period, microcirculatory disturbance will undoubtedly affect the infiltration of inflammatory cells. In the present study, when the postoperative lactate level was less than 4 mmol/L, the lactate level could recover to the normal level within postoperative 12 hours in most cases, and in addition, it could recover to the normal level within postoperative 24 hours in all cases. It seemed that the patients with an initial postoperative lactate level less than 4 mmol/L had too short duration of hyperlactatemia to influence the tissue healing process. As a result, the duration was not associated the RF. On the other hand, in the present study most patients with RF had a duration of hyperlactatemia of more than postoperative 42 hours. The duration was long enough to influence the tissue healing process by influencing invasion of inflammatory cells.
Of course, there seems to be another explanation for the influence of duration of hyperlactatemia on RF. For instance, postoperative surgical stress could lead to metabolic disorders. Hyperlactatemia might be one of the manifestations of metabolic disorders, and other manifestations include hyperdecomposition state and hyperglycemia, which might influence RF. However, in our study, postoperative parenteral nutrition and blood glucose control were strictly conducted. As a result, these influences should be investigated in the further study.
There were limitations to our study. First, as this study was a retrospective study, selection bias existed. Second, the sample size of our study was small, which also led to bias. Third, our data of the postoperative lactate level were collected every 12 hours after definitive surgery. The interval between two measuring points seemed a little long, and this might lead to bias. More accurate postoperative lactate monitoring can be implemented in future prospective studies. In addition, our wards have their own ICU and were managed by surgeons instead of doctors in critical care medicine. Our fluid resuscitation strategy seemed to be conservative (vasoactive drugs are priority). This was likely to have a negative effect on lactic acid recovery.