During the first five days after AHA surgery, we found progressive overhydration, measured by bioimpedance spectroscopy, irrespective of surgical diagnosis. Simultaneously, we observed a progressive increase in preload dependency, as evaluated by passive leg raise, again irrespective of surgical diagnosis.
Overhydration was most prevalent in patients with perforated viscus compared to intestinal obstruction and anastomotic leakage, with a persistent increase in extracellular volume coinciding with fluid administration. The increase in extracellular volume was present irrespective of diagnosis, although most pronounced in patients with perforated viscus. Interestingly, intracellular volume decreased for patients with intestinal obstruction but remained unchanged or slightly increased for perforated viscus and anastomotic leakage.
There is extensive literature on the perioperative fluid status and the impact of overhydration on mortality in critically ill patients [1,2,3]. However, limited data exist  on the perioperative fluid status beyond the immediate post-operative period in patients undergoing AHA surgery. These patients, with a high degree of acute inflammation, sepsis, and fluid disturbances, established even before surgery, share similarities with critically ill patients.
Since patients undergoing AHA surgery may have prolonged derangement of cardiovascular, pulmonary, and gastrointestinal function for days to weeks after primary surgery, judicious fluid replacement is needed to prevent multi-organ failure. In this study, we found that patients with overhydration were less haemodynamically stable, with significantly higher cardiac biomarker proBNP as well as incidence of septic shock, with no difference in preoperative cardiac pathology (Additional file 2: Appendix 2). As such, the haemodynamic instability could indicate either cardiac failure, septic shock, or both. Previously, several studies have found association between elevated proBNP and inflammation, and as such the causality is elusive [31, 32].
There is a consensus that applying GDT in managing perioperative fluid administration in elective surgery could reduce post-operative complications [7, 33]. In contrast, there are conflicting results regarding critical care patients [10, 16, 17], though they do have one thing in common: they focus on the immediate perioperative period with no current data on the potential application of GDT principles to guide fluid therapy beyond this period.
However, while the importance of correct late fluid management cannot be overstated [3, 34], the strategies and monitoring needed are unknown and more complex than elective surgery . Studies in critically ill patients indicate that overhydration is not a problem confined to the early period. Resuscitation fluids comprise less than 10% of overall fluid intake during a whole ICU stay, about 25% are maintenance/replacement fluids, and nearly one-third of the fluid intake consists of “hidden” fluids associated with drug administration, etc. .
We found 16% of all patients undergoing AHA surgery to be significantly overhydrated before the application of a GDT protocol, but 50% of those still responded with a significant increase in SV during the preoperative fluid challenge. There seems to be a physiological incoherence between overhydration and preload dependency throughout the observational period, suggesting vasoplegia and endothelial dysfunction rather than absolute intravascular hypovolaemia as a driver of preload dependency.
The effect of the dyshydration might be diagnosis-specific, with patients with IO presenting with a higher degree of post-operative fluid shifts (Fig. 4). Sepsis-induced vasoplegia and endothelial dysfunction are the expected primary drivers of an increase in ECW , whereas loss of ICW is relatively unexplored.
Although patients with IO presenting with overhydration did have a higher degree of inflammation, as expected , they suffer from water depletion, resulting in hypertonicity in the extracellular space and leading to intracellular dehydration  and secondary protein loss . This could explain the rather steep curve of protein loss in patients with intestinal obstruction compared to patients with perforated viscus and anastomotic leakage.
General and neuraxial (epidural) anaesthesia suppress the sympathetic tone, reducing preload and afterload, potentially inducing or amplifying preload dependency. The effect of an epidural is greatest in the initial post-operative period, where we found no or very low incidence of preload dependency (Fig. 3).
Still, post-operative vasoplegia due to continuous neuraxial blockage and opioid therapy, combined with post-operative inflammatory response, should be considered when assessing preload dependency in a surgical ward. Considering the increasing overhydration during the observational period, our findings show that if we were to apply correction of preload dependency with a fluid bolus as a primary basis for post-operative fluid therapy, as practiced in GDT protocols, we might create unnecessary overhydration.
The inflammatory response was on the downward trajectory by 5th POD (Fig. 4), but there was still progressive increase in preload dependence and overhydration. However, C-reactive protein did not reach baseline levels in patients with intestinal obstruction and perforated viscus and was still at a median value > 100 mg/L in patients with anastomotic leakage. Simultaneously, we observed continuous decline in plasma albumin, indicating that the inflammatory reaction is still present. These findings suggest a need for more extended studies to better understand the trajectory of preload dependency and overhydration and to determine when they start to decline.
During the post-operative period, preload dependency was assessed by passive leg raise, which is a way of challenging preload without administering fluid and thereby avoiding unnecessary fluid administration, provided cardiac output monitoring . Several studies have confirmed the reliability of the passive leg raise with exceptional consistency, and passive leg raise is frequently applied in the ICU departments . A recent meta-analysis found a pooled sensitivity of 85% and a pooled specificity of 91% for detecting fluid responsiveness. We measured stroke volume before and after passive leg raise when the patient has been moved back to the semi-recumbent position to check that it returns to its baseline (data not shown).
Our study has several strengths. This was the first study to assess the fluid status and fluid shifts in patients undergoing AHA surgery, a group equated to the international term emergency laparotomy, beyond the immediate intra- and post-operative period while considering the fundamental pathophysiological differences of diagnosis AHA surgery. This study suggests that specific fluid resuscitation strategies should depend on the diagnosis and highlight the discussion about the place of vasoconstriction therapy in the context of GDT protocols [41, 42].
Limitations of the study include a single-centre study and thus prone to inclusion bias. However, it was a prospective study, and the patient enrolment was unselected. Our results indicate a significant variation in fluid administration, compared to elective surgery, and a considerable amount of fluid is administered. However, there were no data on the indications for post-operative fluid management, which would have been important.
Bioimpedance spectroscopy fluid analysis has been validated in several studies evaluating different patient populations, both elective and emergent [23, 43, 44]. This analysis attempts to measure intra- and extracellular fluid volume and provides absolute and relative fluid overload, but it can be affected by absolute sodium content and thereby overestimate the volume. However, a recent study did find a correlation between the absolute fluid overload measured by bioimpedance spectroscopy and registered weight changes and fluid balance .
In conclusion, despite progressive overhydration throughout the perioperative period, post-operative preload dependency assessed by PLR increased steadily in patients undergoing AHA surgery, indicating a physiological incoherence between fluid status and preload dependence, where patients appeared to be volume deficient but still overhydrated. Considering the increasing overhydration during the observational period, our findings show that an indiscriminate correction of preload dependency with intravenous fluid bolus could lead to overhydration.