Principal findings
In our study, a majority of high-risk surgical patients defined as ASA 3 and ASA 4 were not eligible for an arterial-line-based GDFT approach. The main reasons are methodological limitations of the arterial-line waveform analysis. The majority of patients had to be excluded because a laparoscopic surgical technique was preferred or due to atrial fibrillation.
This study was meant to be a prospective randomized controlled trial with a pragmatic approach to include patients. This would reflect daily routines, strengthening the study. Because the study was conducted in two tertiary hospitals, we had a high amount of high-risk surgical patients. Therefore, we expected to include enough patients in short time to run a well-powered study. Of 732 patients, 224 were not screened for randomisation due to investigator or equipment not being available. If this patient group also could have been screened, we may have had a higher number of patients randomized. However, it is to assume that the same fraction of patients would have to be excluded due to laparoscopic surgery and atrial fibrillation. Therefore, we do not believe that the total amount of patients that could be randomized would be much higher.
We terminated the study early, resulting in a heavily underpowered study. The primary outcome, postoperative morbidity, cannot be assessed since we just included 30 patients, and a statistical analysis would be meaningless. Consequently, we present just the patient flow numbers and not a complete statistical analysis of complications.
The low number of patients that could possibly benefit from GDFT is valid for our hospitals where the surgeons prefer to operate on high-risk patients with minimal invasive surgery. In hospitals that perform a higher amount of open surgery, the use of a minimal invasive GDFT approach may be more feasible.
We define the high-risk surgical patient by the ASA score to make the study pragmatic. However, other authors define “high-risk surgery” or the “high-risk patient” in different ways [
13‐
15]. This makes comparison of trials dealing with this patient group difficult.
Maguire found in a retrospective electronic chart study of his hospital that
n = 12.308 patients underwent surgery in 1 year, but only
n = 4.792 (39 %) fulfilled the criteria for an arterial-line-based cardiac output monitor, and of these, only 23.2 % had an arterial-line. There was no report on how many of the patients were ASA III/IV patients [
16].
Arterial-line-based waveform analysis measures hemodynamics by calculation of stroke volume variation or pulse pressure variation. However, arterial-line-based output methods are not applicable to large patient groups due to their limitations [
16]. One limitation is laparoscopic procedures [
17]. The increased intraabdominal pressure from the pneumoperitoneum affects dynamic parameters independently in changes of volume status [
17‐
19]. Consequently would SVV during pneumoperitoneum increase while the blood volume do not decrease, it would lead to false positive readings [
20]. It is therefore not well validated in humans [
21,
22]. Other limitations of waveform analysis measurements are cardiac arrhythmias and patients with severe cardiac valvulopatias [
23].
Despite criticism about the evidence of the effect of goal-directed therapy, one single method of minimal invasive cardiac output monitoring (Oesophagus Doppler) has even been officially recommended in the National Institute for Health and Clinical Excellence guidelines of the UK (
http://www.nice.org.uk/guidance/MTG3). This decision has been criticized due to the lack of proof [
24,
25], and the method may not be superior to a strategy of a neutral balance [
26]. Other studies have not found benefices in a goal-directed fluid approach [
10,
12,
26‐
30], have not found benefit using a restrictive fluid approach [
31] or even have worse outcome in physically fit patients [
5].
It is biologically plausible that the right amount of fluid given at the right time increase oxygen delivery to the organs and thereby benefit patient outcome. There has been a meta-analysis confirming that a GDFT approach may decrease postoperative complications. However, many included studies are small single centre studies with a high risk of bias or methodological limitations [
1,
32,
6]. The effect on outcome in these studies is mostly small. An even statistical distribution of different studies with a small effect size would consequently result in a number of studies that would show no effect or even harm. The marked overweight of studies with a small positive effect on outcome may indicate a publication bias favouring trials with positive results. This may mask limitations of the arterial-line-based GDFT method that we report. Other studies investigating high-risk surgical patients do not report the exclusion rate due to atrial fibrillation when this condition restricted the GDFT method used [
5,
9].
The OPTIMIZE trial with a study population of 734 patients is the largest trial on GDFT to date. It could not show a reduction of complications after perioperative arterial-line-based GDFT. However, when including the OPTIMIZE trial in an updated Cochrane meta-analysis, it indicates a reduced complication rate [
10].
Goal-directed fluid therapy may be more important in a high-risk surgery population than in a relatively healthy population. Limitations of the method with an arterial-line-based monitor may cause exclusion of a patient group who may benefit most of the treatment. In the UK, it is recommended to use an Oesophagus Doppler to guide fluid therapy preoperatively. The same limitations that apply to the arterial-line-based method (exclusion of patient with atrial fibrillation and laparoscopic procedures) would apply to this method too.