Introduction
Several reports [
1‐
4] have shown that monitoring and maximizing stroke volume by volume loading during high-risk surgery decreases the incidence of postoperative complications and the length of stay in the intensive care unit (ICU) and in the hospital. Unfortunately, this strategy has so far required the measurement of stroke volume by a cardiac output monitor as well as a specific training period for the operators [
5].
By increasing pleural pressure, mechanical inspiration induces cyclic variations in cardiac preload that may be turned into cyclic changes in left ventricular stroke volume and arterial pulse pressure (the difference between systolic and diastolic pressure) [
6]. The variation in arterial pulse pressure (ΔPP) induced by mechanical ventilation is known to be a very accurate predictor of fluid responsiveness; that is, of the position on the preload/stroke volume relationship (the Frank-Starling curve) [
7‐
11]. In brief, in patients operating on the flat portion of the Frank-Starling curve (and hence insensitive to cyclic changes in preload induced by mechanical ventilation), ΔPP is low, and volume loading does not result in a significant increase in stroke volume [
6]. Conversely, in patients operating on the steep portion of the preload/stroke volume relationship (and hence sensitive to cyclic changes in preload induced by mechanical ventilation), ΔPP is high, and volume loading leads to a significant increase in stroke volume [
6]. By increasing cardiac preload, volume loading induces a rightward shift on the preload/stroke volume relationship and hence a decrease in ΔPP. Patients who have reached the plateau of the Frank-Starling relationship can be identified as patients in whom ΔPP is low [
6,
12]. The clinical and intraoperative goal of 'maximizing stroke volume by volume loading' can therefore be achieved simply by minimizing ΔPP [
12].
We performed the present study to investigate whether monitoring and minimizing ΔPP by volume loading during high-risk surgery may improve postoperative outcome.
Discussion
Our study shows that monitoring and minimizing ΔPP by fluid loading during high-risk surgery decreases the incidence of postoperative complications and also the duration of mechanical ventilation, stay in the ICU, and stay in hospital.
Hypovolemia can pass undetected before, during, and after major surgery. Aside from the inevitable losses in the intraoperative period mainly due to bleeding, most patients are still starved for a minimum of 6 hours preoperatively to reduce the risk of acid aspiration syndrome. Additionally, patients undergoing abdominal surgery frequently receive bowel preparation, another factor that may induce or worsen hypovolemia [
17,
18]. In our study population, all patients undergoing bowel surgery (
n = 18) received a bowel preparation (2,000 ml of mannitol solution
per os) administered over a period of 2–3 hours and started 16 hrs before the surgical procedure, and 2,500 ml of glucose solution intravenously over the same period. Other patients (
n = 15) were starved for 12 hours before the surgical procedure and received 1,500 ml of glucose solution intravenously over this period. Classical cardiovascular parameters such as heart rate and arterial pressure are poor indicators of volume status, and these were in the normal range in both groups just before surgery. In contrast, in comparison with values reported previously [
7‐
11], preoperative ΔPP values were quite high (in group I), suggesting that some of our patients were probably hypovolemic at the beginning of the surgical procedure.
Perioperative hypovolemia leading to poor organ perfusion is thought to be a major factor in determining postoperative morbidity after major surgery. Optimization of circulatory status perioperatively was a concept first promulgated by Shoemaker and colleagues [
19]. They found a significant reduction in mortality and stay in hospital in high-risk surgical patients receiving fluid loading with or without dobutamine to increase cardiac output and oxygen delivery to supranormal values. Comparable results from other groups [
20‐
22] using a similar goal-directed approach lends further support to the importance of avoiding hypovolemia and tissue oxygen debt perioperatively.
Instead of targeting a given threshold value of cardiac index or of oxygen delivery during surgery, other authors have proposed to guide intraoperative fluid administration by using individual Frank-Starling curves [
1‐
4,
12,
23]. Several studies have shown that monitoring and maximizing stroke volume by fluid loading (until stroke volume reaches a plateau, actually the plateau of the Frank-Starling curve) during high-risk surgery is associated with improved postoperative outcome [
1‐
4]. The benefit in using such a fluid strategy, guided by the continuous esophageal Doppler measurement of stroke volume, was established first in patients undergoing cardiac surgery [
1] or hip surgery [
2], and was extended more recently to patients undergoing major bowel or general surgery [
3,
4].
Intra-arterial blood pressure monitoring is common practice in most patients undergoing high-risk surgery [
24]. The assessment of ΔPP is therefore a simple and cost-saving method in comparison with technologies monitoring cardiac output or oxygen delivery. Such a simple approach therefore has the potential for widespread application because it is not routinely feasible for anesthetists to monito cardiac output or oxygen delivery in many institutions, as well as in many countries.
Our study has some limitations. First, this is a single-centre trial, and local perioperative standard of care may have influenced the results. There is no specific fluid protocol for high-risk surgery in Santa Casa Misericordia hospital. Anesthetists were free to use the type and the volume of fluid they considered necessary to maintain blood pressure during the surgical procedure, and did not monitor central venous pressure. As a result, group C did not receive HES and received much less fluid than group I during the surgical procedure (the difference between groups was 2,924 ml). The debate over correct intraoperative fluid management is unresolved [
23,
25,
26]. Indeed, facing studies showing a benefit in optimizing stroke volume and oxygen delivery by fluid loading, few studies have conversely shown a benefit in fluid restriction [
27‐
29]. For instance, Nisanevich and colleagues [
29] recently compared the postoperative outcome of two groups of patients undergoing abdominal surgery, a restrictive group (receiving 4 ml/kg of crystalloid solution per hour during the surgical procedure) and a liberal group (receiving a bolus of 10 ml/kg followed by 12 ml/kg per hour during surgery). Patients in the restrictive group received an average total volume of 1,230 ml during the surgical procedure, whereas those in the liberal group received 3,670 ml (that is, 2,440 ml more). The number of patients with complications was smaller in the restrictive group, as was the duration of postoperative stay in hospital. Although the study populations are not comparable (ASA scores were higher in our study), it is interesting to note that the total amount of fluid received intraoperatively by our control group (7 ml/kg per hour) was higher than the volume of fluid received by the restrictive group (4 ml/kg per hour) of Nisanevich's study [
29].
The mortality rate was high in our control group, but we must bear in mind that it was calculated from a small patient population and that most of our patients had many co-morbidities (ASA score was 3 or more in all except six patients; that is, in 82% of our study population). Moreover, it was consistent with mortality rates of patients undergoing high-risk surgery reported previously in Brazil [
21,
30]. In Europe or in the USA, high-risk surgery mortality rates are usually lower [
3,
4,
15,
22], although mortality rates up to 22% [
20] and 34% [
19] have also been reported. In this respect, our findings strongly suggest that an intraoperative goal-directed fluid therapy based on ΔPP monitoring is useful for improving outcome at least in our institution, but caution should be exercised before extrapolating our findings to other patient populations or to other institutions in which standard perioperative fluid management may be different.
The morbidity was high in our patients, with an incidence of postoperative complications of 41% and 75% in groups I and C, respectively. The overall management of our patients may have contributed, at least in part, to this finding. However, one must point out that the incidence of postoperative complications is also directly influenced by the number of complications collected. We used a very extensive list of postoperative complications, including infectious, respiratory, cardiovascular, and abdominal complications proposed recently by Pearse and colleagues [
15], as well as hematologic and renal complications proposed by Bennett-Guerrero and colleagues [
14] and Gan and colleagues [
3]. Finally, the incidence of postoperative complications in our study was comparable to the incidence reported by Pearse and colleagues [
15] in a recent study investigating the value of postoperative optimization in patients undergoing high-risk surgery (44% in the optimization group versus 68% in the control group).
The small number of patients enrolled in this study is also a limitation. Although patients were randomized, we observed that the groups were not comparable in terms of peripheral vascular disease (the incidence was higher in group I). If this finding could not be an advantage to group I, in which a better outcome was finally reported, it indicates the risk of imbalance between the groups as a result of the small sample size. In this regard, because we did not measure ΔPP in the control group, we cannot definitely exclude the possibility that ΔPP might have been different between groups C and I at the beginning of surgery. Our results therefore merit confirmation on a larger scale, and ideally on a multicentre basis. Such a trial is currently ongoing in several hospitals in São Paulo, Brazil. In contrast, the fact that we observed significant differences between the outcomes of two small groups of patients emphasizes the potential value of using ΔPP to tailor fluid administration during high-risk surgery, and the likelihood of observing similar differences in larger populations of patients.
Finally, because ΔPP is directly influenced by the magnitude of cyclic changes in pleural pressure induced by mechanical inspiration, it cannot be recommended as a guide to fluid administration in patients who are not mechanically ventilated with regular tidal volume (for example patients undergoing surgery under regional anesthesia) or when chest compliance is abnormally increased (for example during open chest surgery) or decreased (for example in morbidly obese patients) [
6]. In this regard, it must be noted that these populations were excluded from the present study, as were patients with cardiac arrhythmia, in whom ΔPP cannot be evaluated [
31].
Competing interests
The named authors declare that they have no conflict of interest. Dixtal had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
Authors' contributions
FM, MRL, and JOCA participated in the trial design. VOSP and IPBL obtained the data. MRL, FM, and MAO participated in the data analysis and interpretation of the results. FM and MRL were involved in the statistical analysis and wrote the paper. All authors read and approved the final manuscript.