To our best knowledge, this is the first study to investigate the impact of FRVC on patients with SAP. How to reduce the early inflammatory response of SAP patients is currently a continuous problem during the entire fluid resuscitation period. Unfortunately, there is still no exact way to improve this problem so far. At present, the main role of fluid resuscitation is to maintain hemodynamics through the administration of fluids and electrolytes. In addition to intravenous routes, enteral routes can be used. The enteral routes relied on nasal feeding in the past. However, due to hemodynamic instability and nasal feeding intolerance in the early stage of SAP, the nasal feeding route has not been used for fluid resuscitation. So, on the basis of our successful animal experiments, we tried to use FRVC as a supplement to IVFR.
In our study, the fluid volume of IVFR in the FRVC group was less than that in the non-FRVC group, but the overall fluid resuscitation volume was greater than that in the non-FRVC group. The results suggested that FRVC provided more liquid for aggressive fluid resuscitation. In SAP, increased capillary permeability leads to capillary leakage, which in turn leads to a significant decrease in blood volume. The fluid sequestration level of SAP is higher than that of mild and moderately acute pancreatitis. Therefore, the lack of blood volume in SAP is more serious and fatal. Study by Karin et al. in 2014 revealed that individualized optimization of fluid resuscitation in the early stages of SAP reduces vascular endothelial injury, pancreatic edema and inflammation. The mechanism that the colon actively absorbs water through aquaporin, slows down the absorption of fluid when the blood volume is gradually sufficient. Because of the protective mechanism, more fluid can be put into FRVC without worrying too much about excessive fluid resuscitation. The present study showed significant difference between FRVC and non-FRVC groups in terms of shortening the time of blood volume expansion, suggesting that the speed of fluid resuscitation to reach the goal was significantly increased under the synergistic treatment of FRVC.
Inflammation indicators include WBC, CRP and PCT decreased significantly after FRVC compared to the baseline value. Among them, WBC and CRP declined more significantly in the FRVC group after therapy compared to the non-FRVC group, while the decrease in PCT was not statistically different between the two groups. The inflammatory response which causes multiple organ failure of SAP is related to prognosis. As one of the evaluation indicators of SIRS, WBC is a predictive tool for the severity of acute pancreatitis[20, 21]. CRP has some value in predicting SIRS or death in AP. PCT has also been proven to have the value of predicting the severity and prognosis of SAP and can effectively support the guidance of antibiotic treatment. It is also proved that the combined detection of PCT and CRP has a higher diagnostic value for judging the severity of pancreatitis. Clinical study has shown that reducing the early inflammatory response of SAP patients may improve the condition of patients. FRVC may have a better therapeutic effect on SAP by improving early inflammatory response.
Aggressive fluid resuscitation may cause respiratory complications, electrolyte metabolism disorders and IAH[26, 27]. The rate of mechanical ventilation in the FRVC group were lower than those in the non-FRVC group. Respiratory failure usually occur in the early stage of SAP. A meta-analysis of aggressive fluid resuscitation for acute pancreatitis involving a total of 2626 patients showed that patients receiving aggressive IVFR treatment are at higher risk of acute respiratory distress syndrome (ARDS). At present, the early prevention and treatment of respiratory failure mainly focus on the targeted treatment of risk factors, while other clinical treatment measures that can clearly alleviate ARDS are relatively few. A retrospective study shows that PCT and CRP are significantly increased in SAP patients with ARDS. In our study, the two indicators decreased significantly after FRVC, indicating that FRVC reduced the proportion of mechanical ventilation in SAP patients. This provides us with a new way of thinking that FRVC can be used to reduce lung injury during early fluid resuscitation.
The incidence of hypernatremia in the FRVC group were lower than those in the non-FRVC group. There is still lack of direct evidence on how various types of fluids should be used for fluid resuscitation. In the current fluid resuscitation, crystal fluid is still the primary choice. Research has shown that NS and RL are the most commonly used fluids in fluid resuscitation of acute pancreatitis. The hypernatremia caused by early fluid resuscitation is related to the use of normal saline. In this study, patients used pure water for FRVC had a significantly lower probability of getting hypernatremia. The possible reason is that the osmotic pressure of water is lower than NS or RL. Although the association between the incidence of hypernatremia and increased mortality has been confirmed in critically ill patients, there is currently no sufficient evidence to show that actively correcting hypernatremia caused by fluid resuscitation in critically ill patients has a positive impact on clinical outcomes. However, FRVC provides a potential measure to reduce blood sodium in early stage of fluid resuscitation.
In our study, 49.51% of patients in FRVC group had IAH at the end of BVE. The incidence was not significantly different from the non-FRVC group. Past researches show that the incidence of IAH is between 51%-78% [35, 36]. The amount of crystal fluid used in the initial resuscitation seems to be associated with the risk of IAH, and IAH grade is an important predictor of mortality. Compared with classic IVFR, FRVC did not significantly increase the incidence of IAH. This allows us to infuse more fluid into the colon.
In the current study, FRVC was not significantly correlated with 28-day and 90-day survival and the overall survival rate of SAP is 87.38%. A retrospective cohort study shows that 357 (82.1%) patients survived the 90-day follow-up in a total of 435 SAP patients treated in the intensive care unit. In some other studies, the 90-day mortality of SAP is between 11.9-15.1%[31, 40]. This is consistent with our research results. The survival of SAP is related to many factors, including the severity of the disease, treatment methods and so on[39, 41]. Mohamed et al. show that early aggressive IVFR does not improve the overall incidence of systemic inflammatory response syndrome, persistent organ failure, pancreatic necrosis, and mortality. Age, gender, heart disease, chronic liver failure and laparotomy affect the 90-day mortality. Therefore, this study found that FRVC is a link in the entire SAP treatment process, but it does not play a decisive role in the prognosis.