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Peri-operative goal-directed therapy

A definitive answer remains elusive

Gillies, Michael A.; Pearse, Rupert; Chew, Michelle S.

European Journal of Anaesthesiology (EJA): July 2018 - Volume 35 - Issue 7 - p 467–468
doi: 10.1097/EJA.0000000000000812
Invited commentary
Free

From the Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh (MAG), Adult Critical Care Unit, Royal London Hospital, London, UK (RP) and Department of Anesthesia and Intensive Care, Medical and Health Sciences, Linköping University Hospital, Linköping, Sweden (MSC)

Correspondence to Dr Michelle S. Chew, Department of Anesthesia and Intensive Care, Medical and Health Sciences, Linköping University Hospital, Linköping S-58185, Sweden E-mail: michelle.chew@liu.se

This Invited Commentary accompanies the following original article:

Chong MA, Wang Y, Berbenetz NM, McConachie I. Does goal-directed haemodynamic and fluid therapy improve peri-operative outcomes? A systematic review and meta-analysis. Eur J Anaesthesiol 2018; 35:469–483.

The effect of goal-directed therapy (GDT) on peri-operative outcomes has been studied for more than 4 decades. Despite controversy over the place of this treatment in the practice of modern peri-operative medicine, it remains in widespread use. In this issue of the European Journal of Anaesthesiology, Chong et al.1 present a systematic review and meta-analysis of the effect of peri-operative GDT on postoperative mortality. The authors conclude that GDT decreased morbidity and mortality; however, these findings are tempered by the finding of very poor evidence quality, and trial sequential analysis (TSA) that demonstrates an inadequate sample size to determine the effect of GDT on the primary outcome. Readers may be left wondering what (yet) another meta-analysis contributes to current knowledge in this field. Numerous such studies have been published in recent years and a definitive answer remains elusive. However, the approach to this issue taken by Chong et al. deserves additional consideration. The authors propose that many aspects of the management of high-risk surgical patients and trial methodology have changed over the intervening decades. In particular, the pulmonary artery catheter (PAC), which may be ineffective or even harmful,2,3 has now been superseded by less invasive technologies. Moreover, recent changes in surgical and anaesthetic practice, critical care utilisation and fluid management may also have improved surgical outcomes.

To account for this, the authors adapted their study design: first, the analysis was stratified by use of ‘contemporary GDT’ and the older PAC-guided therapy. As well as the concerns regarding PAC technology itself (many early studies of GDT included the use of a PAC), some of the earlier studies were conducted in an era when clinical trials were still evolving. These considerations, coupled with improvements in control group care over time, are potential limitations of pooling early PAC-guided GDT studies with more contemporary trials in a systematic review. Although this meta-analysis finding suggests that both PAC-guided and contemporary patient groups experienced improvements in mortality, the contemporary group demonstrated much less statistical heterogeneity and positive effects on many postoperative complications, not seen in the PAC group.

The authors also chose several subgroup analyses and secondary outcomes. Although this approach has statistical ramifications, it has been used by authors of other prominent meta-analyses in this area.4 Selecting studies to include in a meta-analysis is often fraught with difficulty and requires a balance of including relevant and comparable studies with strict predefined criteria and an exhaustive search for published data. Subgroup analysis can be a way of reducing clinical heterogeneity within a meta-analysis, particularly if different patient populations, technologies and interventions exist within the literature. The authors’ approach included a number of subgroups and secondary outcomes which have provided some granularity of data within acceptable statistical rigour. Using individual complications as secondary outcomes adds to current knowledge by providing a more nuanced analysis regarding the possible morbidity benefits. Although no firm conclusions may be drawn from the data, Chong et al. suggest that GDT may help to reduce wound and intra-abdominal infections, sepsis, pneumonia, respiratory failure and prolonged mechanical ventilation, acute kidney injury and hospital length of stay. In terms of cardiac morbidity, GDT reduced the frequency of arrhythmias but not cardiac arrest, myocardial infarction or congestive heart failure.

It must be stressed that the authors found the overall quality of the evidence surrounding peri-operative GDT to be poor. The largest trial to date, the OPTIMISE trial,5 did not demonstrate a significant improvement in outcomes, but this may simply be due to a lack of statistical power. Short-term postoperative mortality continues to fall,6 whereas the incidence of postoperative complications remains high and continues to impact on long-term survival and quality of life. Thus, a large trial, powered adequately to assess the effect of GDT on postoperative complications, would seem the logical solution to the current uncertainty.

In summary, this analysis by Chong et al. should be interpreted with caution given the low quality of the evidence, the clinical heterogeneity of included studies and a TSA that demonstrates neither benefit nor futility of GDT. We urgently await the results of robustly designed trials with a low risk of bias which can confirm or refute these findings. The OPTIMISE II7 and FLO-ELA8 trials, which are now under way, promise to provide these definitive answers.

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Acknowledgements relating to this article

Assistance with the commentary: none.

Financial support and sponsorship: MSC has received travel reimbursements and honoraria from Pulsion Medical Systems and Edwards Lifesciences; RP holds research grants, and has given lectures and/or performed consultancy work for Edwards Lifesciences, Intersurgical, Nestle Health Sciences, B. Braun, Glaxo Smithkline and Medtronic.

Conflicts of interest: MAG is a Chief Scientist's Office Scotland NHS Research Scheme Clinician, RP has led several clinical trials in this field, including an ongoing international trial (OPTIMISE II), and is a member of the Associate editorial board of the British Journal of Anaesthesia.

Comment from the Editor: this Invited Commentary was checked by the editors but was not sent for external peer review. MSC is an Associate Editor of the European Journal of Anaesthesiology.

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References

1. Chong MA, Wang Y, Berbenetz NM, McConachie I. Does goal-directed haemodynamic and fluid therapy improve peri-operative outcomes? a systematic review and meta-analysis. Eur J Anaesthesiol 2018; 35:469–483.
2. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med 2003; 348:5–14.
3. Connors AF, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. JAMA 1996; 276:889–897.
4. Grocott MP, Dushianthan A, Hamilton MA, et al. Perioperative increase in global blood flow to explicit defined goals and outcomes after surgery: a Cochrane systematic review. Br J Anaesth 2013; 111:535–548.
5. Pearse RM, Harrison DA, MacDonald N, et al. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA 2014; 311:2181–2190.
6. International Surgical Outcomes Study group. Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries. Br J Anaesth 2016; 117:601–609.
7. http://optimiseii.org/. [Accessed 25 October 2017].
8. http://www.floela.org/. [Accessed 25 October 2017].
© 2018 European Society of Anaesthesiology