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There is continued controversy regarding the benefits of goal-directed fluid therapy (GDT) which requires the use of a cardiac output monitor such as the oesophageal Doppler monitor. Previous evid- ence of improved outcome from GDT in colorectal surgery led to a recommendation from national bodies in the United Kingdom and United States to endorse Doppler-guided GDT as a standard of care in major abdominal surgery, including colectomies1. Its use has also been supported within an Enhanced

Recovery After Surgery (ERAS) program for colonic resection2. However, these earlier studies did not compare GDT directly with fluid restriction, which had also shown improvements in patient outcomes3–5. Recently, two studies have compared fluid restriction to GDT in major colorectal surgery and found no significant difference in outcome between the two techniques6,7. However, there is a much larger body of work supporting GDT, with a total of 32 studies and 2808 patients in a recent review, which found a reduction in mortality and morbidity in high-risk surgery and in morbidity alone in low-risk surgery (identified as a mortality rate <5%)8. There is also a spectrum of GDT protocols with some using fluid therapy alone as the intervention, while others use fluid and inotropes, such as dopexamine, to achieve an oxygen delivery target. Given that both approaches led to a reduction in complication rates in a recent review8, a Doppler-guided, fluid-only

* MB BS, FRCA, FANZCA, Staff Specialist Anaesthetist † MB BS, FRACS, Surgical Fellow, Department of Colorectal Surgery, St

Vincent’s Hospital, Fitzroy, Victoria ‡ BMed, Anaesthetic Fellow § MB BS, FRACS, Visiting Medical Officer, Department of Colorectal

Surgery, St Vincent’s Hospital, Melbourne, Victoria ** MB BS, FANZCA, Staff Specialist Anaesthetist

Address for correspondence: Dr Tuong D. Phan. Email: [email protected] svha.org.au

Accepted for publication on September 2, 2014

A randomised controlled trial of fluid restriction compared to oesophageal Doppler-guided goal-directed fluid therapy in elective major colorectal surgery within an Enhanced Recovery After Surgery program T. D. PHAN*, V. AN†, B. D'SOUZA†, M. J. RATTRAY‡, M. J. JOHNSTON§, B. S. COWIE** Department of Anaesthesia, University of Melbourne, St Vincent’s Hospital, Melbourne, Victoria

SUMMARY There is continued controversy regarding the benefits of goal-directed fluid therapy, with earlier studies showing marked improvement in morbidity and length-of-stay that have not been replicated more recently. The aim of this study was to compare patient outcomes in elective colorectal surgery patients having goal- directed versus restrictive fluid therapy. Inclusion criteria included suitability for an Enhanced Recovery After Surgery care pathway and patients with an American Society of Anesthesiologists Physical Status score of 1 to 3. Patients were intraoperatively randomised to either restrictive or Doppler-guided goal-directed fluid therapy. The primary outcome was length-of-stay; secondary outcomes included complication rate, change in haemodynamic variables and fluid volumes. One hundred patients, 50 in each group, were included in the analysis. Compared to restrictive therapy, goal-directed therapy resulted in a greater volume of intraoperative fluid, 2115 (interquartile range 1350 to 2560) ml versus 1500 (1200 to 2000) ml, P=0.008, and was associated with an increase in Doppler-derived stroke volume index from beginning to end of surgery, 43.7 (16.3) to 54.2 (21.1) ml/m2, P <0.001, in the latter group. Length-of- stay was similar, , P=0.421. The number of patients with any complication (minor or major) was similar; 60% (30) versus 52% (26), P=0.42, or major complications, 1 (2%) versus 4 (8%), P=0.36, respectively. The increased perioperative fluid volumes and increased stroke volumes at the end of surgery in patients receiving goal-directed therapy did not translate to a significant difference in length-of-stay and we did not observe a difference in the number of patients experiencing minor or major complications.

Key Words: fluid therapy, cardiac output, Doppler, colorectal surgery, postoperative complications, monitoring – intra- operative

Anaesth Intensive Care 2014; 42: 752–760

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algorithm would be more practical within an ERAS framework where the use of inotropes requiring central lines and critical care admissions would not be practical. The aim of our study thus was to compare outcomes in elective colorectal surgery between patients having restrictive versus Doppler- guided GDT.

MATERIALS AND METHODS This was a prospective blinded study at the St

Vincent’s Hospital campus, St Vincent’s Public Hospital and St Vincent’s Private Hospital, Fitzroy, Victoria. The study had institutional ethics approval (no. 039/12) and was registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12612000717853.

Enrolment All patients undergoing major colorectal surgery

and enrolled in the local ERAS care pathway were screened for eligibility.

Exclusion criteria included American Society of Anesthesiologists Physical Status 4, pregnancy, in- ability to give informed consent, emergency surgery, significant renal dysfunction (estimated glomerular filtration rate <50 ml/minute), hepatic dysfunction, severe heart failure (New York Heart Association classification 3 or 4), age <18 years and oesophageal pathology (such as varices), which is a relative contraindication to an oesophageal probe.

Randomisation with sealed opaque envelopes was through a computer-generated randomisation sequence and occurred on the day of surgery just prior to the anaesthetic. Randomisation was stratified to either stoma or non-stomal pathway to ensure equal numbers in each group. Colorectal resections that require a stoma have a separate ERAS pathway

to allow for patient education about stomal care. In addition, stomas are more frequently utilised in lower rectal resections which are associated with increased length-of-stay (LOS) and have a higher anastomosis leakage rate9,10. The anaesthetist was not blinded. However, the patient, surgical team and data collectors were.

The patients followed an ERAS clinical care pathway. Patients did not have routine nasogastric tube insertion. Oral fluids were encouraged four hours post-surgery and oral diet commenced from day one. Discharge criteria included resumption of normal diet without nausea or vomiting, return of bowel function, ability to self-care and mobilise independently or be able to be cared for and mobilised by pre-existing care arrangements. Pain needed to be adequately controlled with oral analgesics.

Treatment All patients had a general anaesthetic technique with

muscle relaxant. This consisted of a balanced anaesthetic induction including midazolam, a short acting opioid, propofol and a muscle relaxant. Maintenance was with an inhalational agent (sevoflurane or desflurane). Total intravenous anaesthesia was used if indicated. Epidural analgesia was utilised for planned open surgery if there were no contrain- dications. Transversus abdominal plane blocks were also utilised where appropriate. Intraoperatively, all patients were given intravenous paracetamol and parecoxib unless there was a contraindication. The postoperative analgesia protocol consisted of regular paracetamol, non-steroidal anti-inflammatory drugs and opioid patient-controlled analgesia.

Fluid therapy followed a strict protocol with the restrictive group receiving a set maintenance rate (Table 1). The oesophageal Doppler monitor (ODM) was not used in this group. Previous work has already

Table 1 Fluid protocol for restrictive and Doppler-guided fluid therapy in colorectal patients

Restrictive Doppler-guided

Preoperative Nutricia PreOp* 2 x 200 ml carbohydrate drink (the day before surgery and 2 hrs before surgery)

Nutricia PreOp* 2 x 200 ml carbohydrate drink (the day before surgery and 2 hrs before surgery)

Intraoperative

Preload 0 0

Post induction bolus Up to 5 ml/kg Hartmann’s solution Up to 5 ml/kg Hartmann’s solution

Maintenance 5 ml/kg/hr Hartmann’s solution 5 ml/kg/hr Hartmann’s solution

Boluses Only to replace blood loss or hypotension not responsive to vasopressor

Doppler GDT algorithm with colloid boluses

Postoperative (maintenance) 0.5 ml/kg/hr Hartmann’s solution (with a minimum of 40 ml/hr)

0.5 ml/kg/hr Hartmann’s solution (with a minimum of 40 ml/hr)

*Nutricia, West Ryde, NSW. GDT=goal-directed therapy.

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established that GDT using ODM results in improved stroke volume (SV) and a reduction in corrected flow time compared to a restrictive fluid policy6,7. The GDT group had a similar protocol except during the time of the intraoperative intervention an ODM was utilised to facilitate targeting colloid boluses to fluid responsiveness as indicated by a change in SV index (SVI) >10% and a corrected flow time interval of <350 milliseconds11. Anaesthetists in the intervention group were asked to adhere to the SV optimisation algorithm (Figure 1), which stipulates the admin- istration of a 250 ml bolus of a colloid, although the colloid type was at the discretion of the anaesthetist. This was due to a lack of evidence of efficacy of one type of fluid over another12, although colloids were encouraged as they generally result in greater intravascular expansion13. Crystalloid Hartmann’s solution was used for maintenance. Colloid boluses were starch colloids (4% hydroxyethyl starch, Voluven® or Volulyte® [Fresenius Kabi Pty Ltd, Bad Homburg vor der Höhe, Hesse, Germany] 180/0.3), 4% Gelofusine® (B. Braun, Melsungen, Germany) or 4% human serum albumin. In July 2013, starch colloids were removed from general use at our institution due to safety alerts14.

Postoperative fluids for both groups followed an identical regimen: a maintenance rate of 0.5 ml/kg/ hour Hartmann’s solution (minimum 40 ml/hour) for the first 24 hours with additional boluses allowed for hypotension or urine output <30 ml/hour for four hours.

Measure SVI, FTc (1)

Hypotension OR (2)

SVI <35 mls/m

FTc <360 msec

2

Yes

Yes

No

Yes

250 mls Colloid over 2 mins

10% fall in SVI (5)

≥ 10% increase in SVI (3) Measure SVI every 10 mins (4)

FiGuRe 1: Doppler-guided fluid administration algorithm*. (1) Use the Stroke Volume Index; average over ten cycles. (2) Hypotension can be absolute or relative. (3) A large change in the stroke volume, i.e. >10%, represents the fluid responsiveness. (4) A small change in the stroke volume, i.e. <10%, represents the plateau phase and represents an optimised preload. (5) Once an optimised preload is reached, a fluid bolus should be given if the Stroke Volume Index falls >10%. *The Doppler values will vary from measurement to measurement. However, a trend over several measurements will be more informative. SVI=stroke volume index, FTc=corrected flow time, SV=stroke volume.

Assessed for eligibility (n=131)

Excluded (n=31) Did not meet inclusion criteria (n=24) Refused to participate (n=6) Other reasons (n=1), investigator not available

Randomised (n=100)

Allocated to RES therapy (n=50) Received allocated intervention (n=50)

Lost to follow-up (n=0) Discontinued intervention (n=0)

Lost to follow-up (n=0) Discontinued intervention (n=0)

Analysed (n=50) Excluded from analysis (n=0)

Analysed (n=50) Excluded from analysis (n=0)

Allocated to GDT (n=50) Received allocated intervention (n=50)

A na

ly si

s Fo

llo w

-u p

A llo

ca tio

n En

ro llm

en t

FiGuRe 2: Flow of patients studied. RES=restrictive fluid therapy, GDT=goal- directed therapy.

Table 2 Demographic characteristics and surgical data for restrictive and Doppler-guided fluid therapy groups in colorectal surgery

Item Restrictive (n=50) Doppler-guided (n=50) P-value

Demographic characteristics

Site: St Vincent’s Public/St Vincent’s Private 39/11 40/10

Gender: male/female 31/19 30/20

Height (cm), mean (SD) 169 (8.97) 169 (10.1)

Age (years), mean (SD) 65 (19.9) 63.1 (23.8)

ASA status, median [range] 2 [1–3] 2 [1–3]

Epidural analgesia, n (%) 7 (14%) 6 (12%)

Surgical details

Duration of surgery in min, mean (SD) 228 (98) 238 (89)

Type of surgery, n (%)

Right hemicolectomy 14 (28%) 12 (24%)

Anterior resection 22 (44%) 17 (34%)

Abdominal/perineal 1 (2%) 0

Other 13 (26%) 21 (42%)

Cancer surgery 34 (68%) 29 (58%)

Stoma 14 (28%) 15 (30%)

Surgical approach

Completed by laparoscopy 28 (56%) 31 (62%)

Converted 8 (16%) 8 (16%)

Planned open 14 (28%) 10 (20%)

Comorbidities

Current smoker 9 (18%) 4 (8%)

Ischaemic heart disease 3 (6%) 2 (4%)

Diabetes 5 (10%) 7 (14%)

Congestive cardiac failure 1 (2%) 2 (4%)

Renal impairment Cr >130 µmol/l 0 1 (2%)

Chronic obstructive airways disease/asthma 10 (20%) 7 (14%)

Cerebrovascular accident 0 1 (2%)

Atrial fibrillation 0 5 (10%)

Inflammatory bowel disease 8 (16%) 14 (28%)

Perioperative details

Patient education 45 (90%) 47 (94%)

Oral bowel preparation 15 (30%) 19 (38%)

Rectal bowel preparation 10 (20%) 7 (14%)

Carbohydrate drink 46 (92%) 41 (82%)

Central line 3 (6%) 1 (2%)

Arterial line 47 (94%) 42 (84%)

Tidal volume, ml, mean (SD) 577 (131) 585 (129)

Pathology tests, median (IQR)

Preoperative haemoglobin, g/l 134 (122–145) 130 (120–141) 0.582^

Postoperative haemoglobin, g/l 134 (122–145) 130 (120–141) 0.281^

Preoperative creatinine, µmol/l 73 (63–80) 70 (57–81) 0.773^

Postoperative creatinine, µmol/l 71 (62–81) 62 (56–74) 0.239^

Preoperative albumin, g/l 36 (34–38) 36 (34–38) 0.696^

Postoperative albumin, g/l 28 (25–31) 26 (26–31) 0.311^

^Mann–Whitney U test. SD=standard deviation, ASA=American Society of Anesthesiologists, Cr=creatinine, IQR=interquartile range.

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The ODM was inserted only in the GDT group, with the position and settings optimised for maximal velocity time signal11. The ODM was inserted by the anaesthetist. Readings at the beginning and end of surgery were taken. A locally-adapted postoperative nausea and vomiting guideline was used, based on consensus guidelines15.

Data collection. All postoperative data were collected by a research

nurse or research registrar who was blinded to the allocation. The Clavien-Dindo complications class- ification system was used to categorise complications by type and grade16. Patients were followed up either by phone call or outpatient appointment to determine 30-day mortality and readmission.

Statistics Power analysis was based on the primary

outcome—LOS. With an LOS of eight days (standard deviation 3.5), based on previous local data for colectomies, we estimated that GDT would reduce this by two days, based on earlier studies17. The estimated sample size was 98 (α=0.05, power=0.80). This was increased to 100 to allow for dropouts and exclusions.

Secondary outcomes included number of patients suffering any complication, number of patients suffering from major complications (Clavien- Dindo grade 3 or higher), intravenous fluid volumes administered to patients and change in patients’ haemodynamic parameters.

Continuous data were assessed with Student’s t-test, with graphical and quantitative testing for normality (Shapiro–Wilk test). Non-parametric data were assessed with the Mann–Whitney U test. Haemodynamic parameters were assessed with a paired t-test. Dichotomous data were assessed

using chi-square statistics or Fisher’s exact tests for smaller events (<5) and ranked data were assessed with Spearman’s test for univariable comparisons. All statistical analysis was performed using Stata 12.1 (StataCorp LP, College Station, TX, USA).

RESULTS We consecutively screened all patients eligible for

the ERAS protocol from June 2012 to December 2013. A consort diagram illustrates the flow of patients (Figure 2). Of 131 eligible patients, 100 patients con- sented and were studied. Six refused consent, one did not have an investigator available and 24 did not meet the inclusion criteria. All randomised patients were studied and included in the analysis as intention to treat. There was no loss to follow-up. Demographic characteristics and surgical data for included patients are summarised in Table 2.

There was a laparoscopic surgery rate of 56% for restrictive therapy and 62% for GDT, both consistent with the high proportion of laparoscopic work in this unit. There was also a high proportion of patients (22%) who had inflammatory bowel disease. Stratification ensured equal numbers of each group in the stomal and no stoma pathway.

Fluid volumes were categorised by type and period of administration (Table 3). Compared to the restrictive group, the GDT group had more fluid boluses (121 versus 48), a higher volume of intraoperative colloid (500 [250 to 750] versus 0 [0 to 300] ml, P=0.012) and an overall increased cumulative fluid volume at the end of postoperative day two, (5061 [3860 to 6881] versus 3863 [3132 to 5628] ml, P=0.016).

Standard haemodynamic data for both the restrictive and GDT groups are displayed in Table 4. Doppler parameters at the start and end of surgery are displayed for the Doppler-guided GDT group

Table 3 Fluid volumes, type and period of administration in restrictive and Doppler-guided fluid therapy groups in colorectal surgery (ml)

Intraoperative Post anaesthesia care unit

Ward

In tr

ao p

cr ys

ta llo

id

In tr

ao p

co llo

id

C um

ul at

iv e

in tr

ao p

flu id

to

ta l

B lo

od

pr od

uc t

vo lu

m e

PA C

U fl

ui d

bo lu

s 1

PA C

U fl

ui d

bo lu

s 2

W ar

d po

st op

da

y 0

C um

ul at

iv e

po st

op d

ay 0

to

ta l

Po st

op d

ay 1

to

ta l

Po st

op d

ay 2

to

ta l

C um

ul at

iv e

to ta

l t o

po st

op d

ay 2

Restrictive ml, median (IQR)

1400 (1000–1900)

0 (0–300)

1500 (1200–2000)

0 (0) 0 (0) 0 (0) 670 (450–1095)

2367 (1750–3150)

1070 (950–1549)

538 (0–1090)

3863 (3132–5628)

Doppler- guided

1500 (1000–2000)

500 (250–750)

2190 (1350–2560)

0 (0) 0 (0) 0 (0) 720 (517–1000)

2889 (2250–3450)

1581 (1134–2502)

817 (100–1300)

5061 (3860–6881)

P-value 0.717^ 0.012^ 0.008^ 0.221^ 0.090^ 0.637^ 0.515# 0.037^ 0.002^ 0.676^ 0.016^

#Paired t-test, ^Mann–Whitney U test. PACU=post anaesthesia care unit, IQR=interquartile range.

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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.

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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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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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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REFERENCES 1. National Institute for Health and Care Excellence. CardioQ-

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