EFFECT OF VASOPRESSORS ON FLUID CHALLENGE PERSISTENCE AN OBSERVATIONAL STUDY IN PATIENTS UNDERGOING LAPAROTOMY.

The hemodynamic effect of the fluid challenge administration (FC) depends on different variables related to the interplay between cardiac function and vascular tone response.

In this context, the effect of adding a vasopressor to keep the arterial pressure between predefined ranges may impact on the persistence of stroke volume (SV) changes after FC administration. In fact, both the effect on arterial elastance and venous return may increase the persistence of SV increase, which is know to drop to baseline pre-FC values within fw minutes after FC administration.

This single-centre observational study, in elective patients scheduled for elective laparotomy, hypothesizes that intraoperative norepinephrine infusion would prolong the effect of FC administration.

The appropriate fluid management in the perioperative period is an important, and still partially unclear, chapter of clinical practice for anaesthesiologists. Increasing evidence suggests that intraoperative fluid therapy should be tailored to individual patient's physiology with the purpose of targeting fluid administration to specific stroke volume (SV) responses, or its surrogates. For this reason, small repeated and fast boluses challenging the cardiovascular system should be preferred to continuous and prolonged infusions.

The fluid challenge (FC) is defined as a small amount of fluid given in a short period of time to assess whether the preload reserve of the patient can increase SV with further administration of fluids. A number of studies performed in the operating room evaluated the hemodynamic effects of FC solely considering the effect before and after the infusion. Recently, Aya demonstrated that at least 4 ml kg-1 should be infused to effectively challenge the preload, additionally showing that the hemodynamic effect of the FC is dissipated within 10 minutes, in both responders and in non-responders.

The approach of Aya et al. considers the FC as a drug evoking a systemic response on flow (i.e. SV) and pressure variables \[i.e. systolic arterial pressure (SAP)\]. Accordingly, the pharmacodynamic effect is evaluated by considering the magnitude (i.e. the maximal changes from baseline obtained for a specific variable), the global effect \[i.e. considering the area under the curve (AUC) obtained by plotting the changes overtime\] and the persistence of the hemodynamic response after the end of FC administration. The infusion time of FC administration, which ranges in the literature between 5 and 30 minutes, may influence the magnitude of SV response and, in turn, the amount of patients defined as fluid responders . Since several intraoperative pathways of hemodynamic optimization are based on the response to repeated FCs, a prolonged infusion time may potentially affect fluid responsiveness and, in turn, wrongly drive intraoperative fluid management and eventually affect postoperative outcomes.

Since FC is a test embedding at least three variables (i.e. the amount of fluid; the time needed to complete the administration and the SV change threshold used to define a positive response), the role of a one single component on the final outcome can be addressed only by keeping fixed the others. Our group recently investigated the role of the infusion rate in a multicentre study (under revision at the timing of writing this protocol) and our research is now focused on the assessment of the role of the vascular tone in the persistence of the FC effect overtime. The previous study demonstrated that the rate of infusion impact on FC response, however another crucial issue is related to the persistence of the effect of the FC on the SV. In fact, the SV is determined by the interplay between cardiac function and arterial load. Diastolic filling depends on venous return, which is determined by the "stressed volume" and venous compliance. Systolic cardiac function depends on both cardiac factors and arterial load and is predominantly determined by arterial elastance (Ea) and resistance. For this reason, the effect of a vasopressor (i.e. the norepinephrine, the most widely used) may impact on the persistence of the increase of the SV after FC administration.

This single-centre observational study, in elective patients scheduled for elective laparotomy, hypothesizes that intraoperative norepinephrine infusion would prolong the effect of FC administration.

Eligibility Criteria:
Inclusion Criteria:

* adult patients, scheduled for elective laparotomy (\>3h predicted) and requiring a FC.

Exclusion Criteria:

* any recurrent cardiac arrhythmia;
* reduced left (ejection fraction \< 30%) or right (systolic peak velocity of tricuspid annular motion \< 0.17 m/s) ventricular systolic function.

Once enrolled, the patient can be additionally excluded due to the occurrence of one of the following intraoperative conditions:

1. significant bleeding (more than 500 ml in ½ hour)
2. recurrent extrasystoles
3. persistent low quality of the arterial signal affecting hemodynamic monitoring measurements
4. intraoperative hemodynamic instability requiring the persistent use of vasopressors.