FLUID RESTRICTION COMPARED TO DOPPLER-GUIDED THERAPY

FLUID RESTRICTION COMPARED TO DOPPLER-GUIDED THERAPY

FLUID RESTRICTION COMPARED TO DOPPLER-GUIDED THERAPY

Anaesthesia and Intensive Care, Vol. 42, No. 6, November 2014

alone. There was a significant increase in the SVI in the Doppler-guided group from the start to the end of surgery, (43.7 [16.3] to 54.2 [21.2] ml/m2, P <0.001) and an increase in corrected flow time (346 [45] to 381 [54] milliseconds, P <0.001).

The primary outcome, LOS, was similar between the two groups, with the restrictive group median of 6 (4 to 9) versus the GDT median of 6.5 (5 to 9), P=0.421 (Table 5). Medically ready for discharge LOS (Table 5) was also estimated to account for when patients had met predefined ERAS discharge criteria—this allows separation between medical and non-medical reasons for a delayed hospital discharge.

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Complications were the secondary outcome and did not show a significant difference in terms of the proportion of patients suffering any complication

(52% [26 patients] versus 60% [30 patients]) (Table 5). The proportion who had major complications (Clavien-Dindo grade 3 to 5) was also not statist-ically different (restrictive 8% [four patients] versus GDT 2% [one patient]). The count of major complications, which reflects more than one complication in some patients, showed a larger number of major compli- cations in the restrictive group (nine versus one, P=0.007) (Table 6). There was one death in the restrictive group. This patient had a laparoscopic ultra-low anterior resection with ileostomy and had an uneventful immediate postoperative course until day three, when he developed nausea and vomiting and later had a cardiorespiratory arrest. There were no deaths in the GDT group (the study was not adequately powered to assess these secondary out- comes, so no firm conclusions can be drawn here).

DISCUSSION ERAS

programs incorporate specific intraop-

erative and postoperative fluid regimens that have been identified as key components for successful implementation18. There are differing fluid therapy protocols that have been used within ERAS. In the study by Muller et al, fluid restriction had been used. However, there is some evidence that suggests fluid restriction may increase morbidity in major abdominal surgery. Holte et al found a trend towards increased complications in a restrictive fluid therapy group and called for further studies looking at fluid optimisation using GDT19. Futier et al found that GDT with restriction increased morbidity compared to GDT with liberal fluid therapy20. Zakhaleva et al compared Doppler-guided GDT with a liberal fluid therapy in 91 patients and found a significant difference in complication rate in favour of GDT (22% versus 49%, P=0.022), although this did not result in an improvement in LOS21. In contrast, two

Table 4 Haemodynamic data of restrictive or Doppler-guided fluid therapy in colorectal patients

Restrictive Doppler-guided

Start End P-value Start End P-value

SBP, mmHg, mean (SD) 108 (19) 116 (21) 0.107# 101 (23) 106 (28) 0.158#

MAP, mmHg, mean (SD) 76 (17) 82 (15) 0.126# 68 (21) 68 (28) 0.986#

HR (bpm), mean (SD) 71 (14) 67 (11) 0.127# 73 (20) 65 (22) 0.033#

ODM-SVI, ml/m2, mean (SD) 43.7 (16.3) 54.2 (21.2) <0.001#

ODM-CI, l/min/m2, mean (SD) n/a n/a 3.23 (2.63) 3.45 (1.21) 0.554#

FTc, ms, mean (SD) 346 (45.6) 381 (54.1) <0.001#

#Paired t-test. SBP=systolic blood pressure, MAP=mean arterial pressure, HR=heart rate, ODM- SVI=oesophageal Doppler-monitored stroke volume index, ODM-CI=oesophageal Doppler-monitored cardiac

index, FTc=corrected flow time.

Table 5 Outcomes of restrictive compared to Doppler-guided fluid therapy in

colorectal patients

Restrictive Goal- directed

P-value

LOS, days

median (IQR 1–3) 6 (4–9) 6.5 (5–9) 0.421^

Medically ready LOS, days

median (IQR 1–3) 6 (4–9) 6 (5–9) 0.485^

Complications % (number)

Any complication (Clavien-Dindo grade 1–5)

52 (26) 60 (30) 0.420*

Major complication (Clavien-Dindo grade 3–5)

8 (4) 2 (1) 0.362**

Readmissions 2 (1) 10 (5) 0.204**

Deaths 2 (1) 0 1.0**

*Chi-squared test **Fisher’s exact test, ^Mann–Whitney U test. LOS=length-of-stay, IQR=interquartile range.

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Anaesthesia and Intensive Care, Vol. 42, No. 6, November 2014

recent studies found no significant difference when GDT was compared to fluid restriction alone6,7.

Our hypothesis was that GDT would confer an advantage compared to fluid restriction alone within an ERAS clinical care pathway. This is one of the few studies that has included a significant number of low rectal resections with stoma, which are associated with greater morbidity and increased LOS9. We have sought to be comprehensive in reporting of all complications, including minor complications that may impair recovery but were not collected in earlier studies7.

The GDT group had an increased SVI and systolic flow time by the end of surgery. Additionally, GDT patients received a greater frequency of fluid boluses (121 versus 48), which would be consistent with successful implementation of a GDT algorithm. Importantly, the GDT optimisation of intraoperative haemodynamics was achieved within a framework of overall fluid restriction. Both the restrictive and GDT groups in our study would fit within the definition of ‘restrictive’ suggested by Rahbari et al with low intraoperative and perioperative fluid totals22. This is in contrast to a study by Challand et al, where a mean volume of 5339 ml23 (compared to 2190 [1350 to 2560] ml in our GDT group) was

administered intraoperatively. Challand et al found a trend of increased LOS in the GDT compared to a standard control in aerobically fit patients, raising the possibility that any benefit from optimised haemodynamics from GDT was offset by excessive fluid administration. In contrast, the GDT algorithm and perioperative fluid protocol utilised in this study avoided excessive fluid load, but allowed for individualised titration of fluid boluses.

Despite the achievement of haemodynamic goals and minimisation of fluid excess, GDT in this study did not confer any significant clinical advantage within an ERAS pathway. There was no difference in LOS or medically ready for discharge time. There was also no difference in patients experiencing minor and major outcomes. A lack of benefit from GDT relating to minor outcomes, such as hypotension or oliguria, suggests that fluid restriction is close to optimal fluid therapy and we would agree with Srinivasa and Brandstrup et al that GDT within an ERAS framework has no clear evidence of incremental benefit in terms of LOS and reducing overall complications6,7.

One of the secondary outcomes was a finding of a significant reduction in the number of major complications favouring GDT (restrictive 9 versus

Table 6 Major and minor complications of restrictive compared to Doppler-guided fluid therapy in colorectal patients

Clavien-Dindo complication type Minor complications (Clavien-Dindo grade 1–2)

number

Major complications (Clavien-Dindo grade 3–5)

number

Restrictive Goal-directed Restrictive Goal-directed

1 Blood transfusion 1 1 2

2 Postoperative nausea and vomiting 11 7

3 Pain 2 3

4 Anastomotic leak 1 1

5 Prolonged ileus 7 10

6 Wound breakdown, dehiscence, infection 2 1 1

9 Congestive heart failure 2

10 Arrhythmia 4

11 Hypotension 4 4 1

12 Sepsis 1

13 Pneumonia 1 1

14 Acute kidney injury 1 2

15 Urinary tract infection 1

16 Neurologic 1 3

17 Others 7 12 1 1

Total complication count 38 40 P=0.87* 9 1 P=0.007**

*Chi-squared test, **Fisher’s exact test. LOS=length-of-stay.

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Anaesthesia and Intensive Care, Vol. 42, No. 6, November 2014

GDT 1, P=0.007), but which represented a non- significant difference in the number of patients (restrictive 4 versus GDT 1, P=0.362). While there may be an association, this data alone is insufficient to draw a conclusion of benefit for GDT. Nevertheless, it is notable that while both groups did very well with a low rate of major complications, only one patient in the GDT group suffered a major complication. It is possible that the treatment effect of Doppler-guided fluid therapy is more modest and cannot be readily demonstrated over and above the improved outcomes associated with ERAS, in- cluding reduced LOS and fewer complications2.

This study does not refute the benefit of the selective use of GDT in a higher-risk group where the benefits have been demonstrated in terms of reduction in major complications8. However, there are no studies to date which have identified a high-risk patient group within an ERAS program. Additional information may be provided by current trials such as the Restrictive Versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) study, which is a large multicentre randomised control trial of 2800 patients currently being undertaken that will look primarily at restrictive compared to liberal fluid therapy in a major abdominal surgery study24. It will also observe the effect of goal-directed therapy in a subgroup and will hopefully yield important infor mation from this high-risk group that includes patients over 70 years old and those who have major comor- bidities. Similarly, higher-risk colorectal procedures such as rectal resections may be a better target for GDT.

This study has been deliberate in targeting patients suitable for an ERAS program, which constitute the bulk of elective colectomies, giving it greater generalisability within a colorectal unit. We have tail- ored the outcomes to include minor complications, such as significant hypotension, postoperative nausea and vomiting and gastrointestinal morbidity, which are more common and have the potential to delay recovery in otherwise well patients. The findings are specific to within an ERAS program that emphasises preoperative carbohydrate drinks and early oral postoperative fluid intakes (caution should be exercised extrapolating the results outside of such a program).

While we were unable to demonstrate a benefit in terms of LOS from GDT compared to restrictive fluid therapy, this study was not powered to detect difference in LOS <2 days. For example, if a one- day reduction existed, it could have been missed. Similarly, we cannot be sure about the absence of

differences in major complications. Nevertheless, the findings in this study do not support earlier GDT studies that showed marked improvements in outcome, including a reduction in LOS and reduction in complication rate favouring GDT17. The lack of a significant treatment effect may reflect different perioperative practices between earlier studies and contemporary practice. Some major changes may include greater utilisation of laparoscopic surgery25, more limited surgical incisions, carbohydrate drink administration and early enteral fluid and feeding2. The changes in perioperative practices can clearly be seen when comparing a mean LOS of 12 days for the control group by Noblett et al in 2006 with a median LOS of six (four to nine) days in this study26.

Subgroup analysis of patients with stomas (compared to patients with no stoma) was not performed, as there was only a modest trend of increased LOS which was not statistically significant. This makes it unlikely that there would be a difference between restrictive fluid therapy and GDT in stomal patients alone. Sim- ilarly, there was no apparent significant difference in LOS among patients with inflammatory bowel disease.

We found that GDT was associated with an increased SV after fluid optimisation with the Doppler monitor. However, this did not result in a significant difference in the LOS and we did not observe a difference in the number of patients experiencing minor or major complications. This suggests that increasing global oxygen delivery with fluid therapy alone in this group of elective colorectal surgery patients was not beneficial. Future work should focus on GDT in higher-risk patients or in higher-risk surgery.

FUNDING This study was supported by a St Vincent’s Hospital

Research Endowment Fund 2012, AUD $20,000.

ACKNOWLEDGEMENTS AND DECLARATIONS

The conduct of the study was reliant on Ms Petrea

Corcoran and Ms Simone Said for recruitment and research support. Dr Vanida na Ranong assisted with the study protocol. Statistical support was given by Dr Roman Kluger and Associate Professor Lisbeth Evered. We thank them for their time and expertise.

An abstract of this study was accepted and presented at the Australian and New Zealand College of Anaesthetists’ Annual Scientific Meeting, Singapore, on 8 May 2014.

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FLUID RESTRICTION COMPARED TO DOPPLER-GUIDED THERAPY