This article is accompanied by the following Invited Commentary:
Gillies MA, Pearse R, Chew MS. Peri-operative goal-directed therapy: A definitive answer remains elusive. Eur J Anaesthesiol 2018; 35:467–468.
The concept of peri-operative goal-directed haemodynamic and fluid therapy (GDT) has its origins in the seminal study by Shoemaker et al.1, where patients who received preoperative haemodynamic optimisation titrated to explicit goals of end organ blood flow had improved outcomes. Over the decades, GDT has remained a high area of interest in peri-operative study, with the publication of nearly 100 randomised controlled trials (RCTs) since the 1990s alone.1–95 In contrast to care guided by traditional vital signs, the principle underlying GDT is that the administration of fluid and vasopressors be guided by explicit targets that reflect end organ blood flow, such as cardiac index (CI), stroke volume (SV) variation (SVV) or oxygen delivery (DO2).96 Historically, such indices were measured by pulmonary artery catheters (PAC), but recently less invasive technologies have become widely available.97 Such contemporary GDT devices derive measurements using a variety of methods from transpulmonary indicator dilution to arterial waveform analysis. These are summarised in Table 1.97
Given the clinical importance of GDT and its potential to improve patient outcomes, investigating whether or not these interventions are truly effective is worthwhile. However, existing reports and meta-analyses have demonstrated conflicting results.98–101 Significantly, several significant limitations of methodology have been repeated across these older reports, such as missed studies,98,99 pooled complications as an artificial composite with the risk of double-counting of events98,102 and exclusion of certain types of surgery or patient groups.98–101 Finally, several authors have pooled PAC-guided GDT studies with those using contemporary GDT devices.98,103
To address the limitations of existing publications, we performed an updated systematic review and meta-analysis of peri-operative GDT. We hypothesised that peri-operative GDT would improve mortality (primary outcome) and morbidity (secondary outcomes) in adult surgical patients when compared with standard care. Although use of PAC is historically of interest with regard to GDT, we postulated that those generally older studies would have significant methodological differences from modern studies, such as the initiation of GDT preoperatively, and would not reflect current practice.1 Under these more rigorous methodological conditions, we wondered whether the benefits of GDT identified in older analyses would persist.98,103
The current systematic review and meta-analysis complies with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.104 Our institutional research ethics board does not require approval for systematic reviews and meta-analyses.
MEDLINE, EMBASE and the Cochrane Library were searched without language restriction from inception to 31 December 2016 for RCTs that recruited adult surgical patients receiving peri-operative GDT versus standard care and that reported at least one clinical outcome of interest.
For inclusion, studies had to recruit adult surgical patients having elective, urgent or emergency surgery. Although both cardiac and noncardiac surgery were of interest, we excluded studies recruiting exclusively trauma patients, parturients and nonsurgical critical care patients.
Subjects had to be randomised to either a standard of care or GDT. We defined GDT as any fluid and/or vasopressor therapy titrated to haemodynamic targets that included the following: SVV, pulse pressure variation (PPV), CO or CI, SV or SV index, central venous oxygen saturation, DO2 or DO2 index, oesophageal Doppler flow corrected time, echocardiography assessment and oxygen extraction ratio (O2ER). These targets were chosen as they are well studied and, in the context of the conflicting evidence base, there is some suggestion that their optimisation improves outcome.97,103 If investigators used an Enhanced Recovery After Surgery (ERAS) Programme, both study arms must have been receiving the ERAS care. With regard to the control arm therapy, we excluded studies where the control arm was also receiving a form of GDT, such as trials comparing two different GDT devices or those comparing different GDT targets. We accepted standard care in the form of protocol-driven standard care (e.g. maintain mean arterial pressure > 65 mmHg), care at the discretion of the attending physicians with no formal protocol or protocols involving restrictive fluid strategies.
The primary outcome was in-study mortality. Secondary outcomes included organ-specific morbidity, such as myocardial infarction (MI), arrhythmia, cardiac arrest, congestive heart failure (CHF), acute kidney injury (AKI), pulmonary embolus, infections, stroke or transient ischaemic attack (TIA) and surgical complications. Furthermore, exposure to allogenic packed red blood cell transfusion and hospital and ICU length of stay (LoS) were of secondary interest.
The full search strategy is available online (Supplemental Digital Content 1, Search Strategy Appendix, http://links.lww.com/JCM/A115). The search used a comprehensive combination of medical subject heading terms and free-text terms and synonyms. The reference lists of included articles and older reviews were manually searched for additional studies. Unpublished data were not sought. To avoid publication bias, grey literature (e.g. conference abstracts) was included in the systematic review.
Article screening, data extraction and risk of bias assessment
Studies were screened independently by MC and YW and any discrepancies resolved by consensus with IM. A similar process was used for the data extraction. Extracted data included baseline demographic data, study descriptors and predefined clinical outcomes. The risk of bias assessment was conducted using the Cochrane Risk of Bias Tool.105 The tool defines several sources of bias and provides a standardised approach for assessment. The specific domains include random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (performance bias), complete reporting of data and with low-to-minimal loss to follow-up (attrition bias), selective reporting bias and other bias.105 Studies were considered to be at low risk of bias if they adequately met the first five criteria with no evidence of significant selective reporting bias or any other major sources of bias. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology was used to appraise the overall evidence base quality for each outcome.106
Stata (Version 13.1; StataCorp, College Station, Texas, USA) was used for statistical analysis. Binary outcomes were reported as odds ratios (ORs). Continuous outcomes were reported as the weighted mean difference (WMD) or standardised mean difference, where appropriate. Both types of data were presented with their corresponding 95% confidence intervals (95% CI). We anticipated clinical heterogeneity among the devices and methods used to provide GDT, and therefore, a random-effects analysis model was selected. For statistically significant outcomes, the number needed to treat to benefit one patient (NNTB) or number needed to treat to harm one patient (NNTH) were calculated, where appropriate. All data are reported with a significance level of α = 0.05. Heterogeneity was estimated using the I2 statistic and the χ2 test for statistical significance. We considered an I2 value from 50 to 70% to be moderate heterogeneity and 70% or higher to be high heterogeneity. Stratification of outcomes based on PAC versus other technologies was planned a priori. Furthermore, all subgroup analyses were prespecified according to hypothesised sources of heterogeneity and included: type of surgery (e.g. cardiac versus noncardiac surgery), type of fluid (e.g. colloid versus crystalloid), fluid versus fluid and vasopressors to achieve goals, presence of ERAS program, risk of bias and technology used to achieve the GDT. Publication bias was assessed via Egger's regression and visual inspection of the data on a funnel plot.
In the context of many meta-analyses, repeated significance testing of pooled data can lead to the possibility of Type 1 errors.107,108 Trial sequential analysis (TSA) is a statistical technique that allows the creation of trial sequential boundaries within a cumulative meta-analysis to determine whether a P value is sufficiently small to show an effect or futility.107,108 TSA was used to assess the maturity of the evidence base for the primary outcome of mortality. To perform the TSA, we assumed a two-tailed α of 0.05, β of 80% and a relative risk reduction of 20% from the control group event rate. The TSA was performed with version 0.9.5.5 Beta. Other authors have provided excellent descriptions of TSA, and full discussion is beyond the scope of this systematic review.108
Literature search and study selection
The search initially retrieved 1945 citations with 95 RCTs (11 659 patients) meeting the inclusion criteria (PRISMA Flowchart, Fig. 1).1–95 Eight small RCTs (400 patients) did not report extractable outcomes and, therefore, could not be pooled for meta-analysis.2,8,17,19,49,54,86,95 A description of excluded studies is provided in the supplemental content (Supplemental Digital Content 2, Table of Excluded Studies, http://links.lww.com/JCM/A115).
Baseline characteristics of included randomised controlled trials
The salient baseline characteristics of included RCTs are shown in Table 2. Only four of 95 studies were considered to be at low risk of bias, given the challenge in blinding participants during the performance of GDT in the peri-operative period (Risk of Bias Assessment, Supplemental Digital Content 3, Risk of Bias Assessment and Risk of Bias Distribution, http://links.lww.com/JCM/A115, Fig. 2).36,51,76,84 Notably, 12 studies recruited cardiac surgery patients, with the rest recruiting noncardiac surgery patients.19,22,31,38,40,42,47,57,58,60,66,70 Thirteen studies used a PAC to guide therapy.1,3,11,12,18,25,28,31,60,83,87,90,93 The remaining studies of more modern GDT devices/technologies used oesophageal Doppler (23 studies),10,13,14,17,20,21,23,24,32,33,41–43,46,47,68,71,74,76,78,79,82,86 noninvasive CO monitoring (e.g. arterial waveform-derived CI or SVV; 52 studies),2,4–6,8,9,15,16,19,22,26,27,29,30,34–40,44,48,49,51–55,57–59,61–67,69,70,73,75,77,80,81,84,85,88,91,92,95 and miscellaneous technologies (e.g. PPV, laboratory measurements of O2ER or echocardiography; seven studies).7,45,50,56,72,89,94 All results are presented according to the predefined analysis plan and stratified by PAC use versus the more contemporary technologies.
Results for contemporary goal-directed haemodynamic and fluid therapy
Primary outcome: in-study mortality
GDT guided by modern technology resulted in lower in-study mortality compared with standard care (OR 0.66; 95% CI, 0.50 to 0.87; P = 0.004; NNTB = 59 or 18 events prevented per 1000 patients; I2 = 0.0%; N = 52; Supplemental Digital Content 4, http://links.lww.com/JCM/A115, Forest Plot of Mortality for Modern GDT). These benefits persisted across subgroup analysis in the highest risk patients (OR 0.60; 95% CI, 0.42 to 0.85; P = 0.004; NNTB = 34), the highest risk procedures (OR 0.69; 95% CI, 0.51 to 0.95; P = 0.02; NNTB = 75), and among studies where the GDT was initiated intra-operatively (OR 0.65; 95% CI, 0.47 to 0.89; P = 0.007; NNTB = 59). A full summary of the sensitivity analyses is shown in Table 3. Notably, the mortality reduction was not statistically significant in the subgroup of studies employing fluid-only GDT, but remained significant among studies where no industry relationship was apparent (Table 3). Given that only four studies overall could be definitively judged at low risk of bias, subgroup analysis by risk of bias was insufficiently powered.36,51,76,84 With regard to TSA, the cumulative z-curve did not cross the trial sequential monitoring boundaries nor enter the region of futility (Supplemental Digital Content 5, Trial Sequential Analysis, http://links.lww.com/JCM/A115). In the context of TSA, this suggests that the cumulative sample size is inadequate to definitively determine the impact of GDT on peri-operative mortality and that further trials have the potential to alter the magnitude and/or direction of effect.
Secondary outcomes: organ-specific morbidity
All binary secondary outcomes are listed in detail in Table 4.
Contemporary GDT reduced rates of arrhythmia (OR 0.70; 95% CI, 0.55 to 0.91; P = 0.006; NNTB = 34). MI, CHF and cardiac arrest were not significantly different between groups (Table 4).
Rates of respiratory failure and prolonged mechanical ventilation were reduced in patients receiving GDT (OR 0.54; 95% CI, 0.35 to 0.84; P = 0.006; NNTB = 26). Furthermore, rates of pneumonia were reduced with GDT compared with standard care (OR 0.69; 95% CI, 0.51 to 0.92; P = 0.01; NNTB = 38).
Other infectious outcomes
Wound infection (OR 0.48; 95% CI, 0.37 to 0.63; NNTB = 19) and intra-abdominal infection (OR 0.65; 95% CI, 0.45 to 0.93; NNTB = 35) rates were reduced in patients receiving GDT. In addition, rates of sepsis were also reduced in the GDT arm compared with standard care, but only 13 studies reported this outcome (OR 0.55; 95% CI, 0.33 to 0.91; P = 0.02; NNTB = 43). The incidence of urinary tract infection was similar between groups (Table 4).
GDT patients had reduced rates of AKI versus standard care (OR 0.73; 95% CI, 0.58 to 0.92; P = 0.007; NNTB = 29). No significant difference was detected for stroke or pulmonary embolism between groups. Likewise, surgical complications were similar between groups in terms of anastomotic leak and ileus or bowel obstruction. Finally, exposure to allogenic blood was not different between arms.
Secondary outcomes: healthcare length of stay and other continuous outcomes
Continuous outcomes are summarised in Table 5.
Length of stay
Across the 62 RCTs reporting hospital LoS, contemporary GDT reduced LoS (days) compared with standard care by −0.90 (95% CI, −1.32 to −0.48), with very high statistical heterogeneity (I2 = 81.2%). Similarly, ICU LoS was also reduced (−0.69; 95% CI, −1.00 to −0.37; I2 = 83.8%).
Time to recovery of bowel function
The time to first flatus (days) was reduced by modern GDT by −0.37 (95% CI, −0.59 to −0.14; I2 = 74.1%), but there were no differences in the time to first oral intake or bowel movement detected. Statistical heterogeneity was high among all these analyses (Table 5).
Results for pulmonary artery catheter-guided goal-directed haemodynamic and fluid therapy
Mortality was reduced among all 13 studies that used a PAC to guide the GDT (OR 0.53; 95% CI, 0.30 to 0.92; P = 0.004; Supplemental Digital Content 6, http://links.lww.com/JCM/A115, Forest Plot of Mortality for PAC-guided GDT), but this effect did not persist in the largest and most rigorously conducted study.28 There were no other differences in any of the other secondary outcomes among the PAC studies, including morbidity and LoS (Tables 4 and 5).
The primary outcome (in-study mortality) was assessed for publication bias with Egger's regression, and a funnel plot was constructed and inspected for asymmetry. Egger's regression was not significant (P = 0.59) and the funnel plot appeared symmetrical on visual inspection, which suggests a low probability of publication bias.
Results of nonmeta-analysable studies
Eight small RCTs (400 patients) could not be pooled due to lack of extractable outcomes, and all of these studies were conference abstracts not yet published at the time of our literature search.2,8,17,19,49,54,86,95 Of these, some found no difference between GDT and standard care.2,19 Others found modest differences such as decreased hospital LoS,8,86 faster recovery of bowel function,17 reduced ‘major abdominal complications’,49 reduced mortality (albeit statistical analysis is not presented)54 and reduced lactate levels.95
Contemporary goal-directed haemodynamic and fluid therapy
This comprehensive systematic review and meta-analysis of 95 RCTs demonstrates that contemporary GDT modestly improves in-study mortality in non-trauma and nonpregnant adult surgical patients (OR 0.60; 95% CI, 0.50 to 0.87; NNTB = 59; P = 0.004; N = 52). The overall results are found in the Summary of Findings Table, with the corresponding GRADE recommendations (Table 6).106 Based on the articles included in this analysis, these numbers suggest that for every 1000 patients treated with GDT, 18 (95% CI, 7 to 26) deaths would be prevented. In reference to the subgroup analyses performed, the mortality benefits were most pronounced in high-risk patients (NNTB = 34), present among trials where the GDT was initiated intra-operatively (NNTB = 59), and persisted among large trials recruiting more than 100 patients (NNTB = 59). In contrast and perhaps in part due to lack of statistical power, the benefits were not statistically significant in cardiac surgery trials or studies involving emergency surgery, and they seemed to be reliant on the use of vasoactive agents as part of the GDT. Furthermore, with regard to the device used to achieve the GDT, the minimally invasive CO monitor category was the only significant modern subgroup. Finally, although statistical heterogeneity was low (I2 = 0.0% for the primary outcome), clinical heterogeneity is still a real concern given the variety of GDT technologies, haemodynamic goals and protocols employed. Taken together with the high risk of bias, modest absolute risk reduction and inconclusive TSA, the results should be interpreted with caution.
Secondary benefits of modern GDT included 30 (95% CI, 10 to 47) fewer cases of arrhythmia, 27 (95% CI, 7 to 43) fewer cases of pneumonia, 55 (95% CI, 39 to 67) fewer cases of wound infection and 35 (95% CI, 11 to 55) fewer cases of AKI per 1000 patients treated with GDT (Table 6). Significantly, the rate of AKI was reduced despite 71 of 95 GDT studies using colloid boluses (Table 1), which have been demonstrated to be harmful in critical care patients.109 Despite increased fluid administration in the GDT group overall, there was no difference in CHF or MI. Hospital and ICU LoS were also reduced with GDT, albeit the statistical heterogeneity in this analysis was very high.
Pulmonary artery catheter-guided goal-directed haemodynamic and fluid therapy
Given the significant limitations among the trials that used PAC-guided GDT, together with improvements in the conduct of clinical care and trial design that have taken place over recent decades, it is perhaps not surprising that data for the PAC studies were systemically different from modern studies. It is for this reason that these data were presented separately. In this context, PAC-guided GDT reduced in-study mortality in older trials that mainly involved preoperative optimisation – but not in the most rigorous and well conducted study.28 With regard to secondary outcomes, there were no differences for the PAC-guided GDT studies.
In addition to being more invasive than contemporary GDT technologies, there is a lag time between the decision to place a PAC and actual insertion; furthermore, the plethora of haemodynamic data derived from a PAC must be integrated, interpreted and then applied to patient care.97 For all these reasons, reinforced by our findings, contemporary practice does not place a great value on the role of PAC for intra-operative monitoring.110,111
Differences from previous reviews
Given the clinical importance of peri-operative GDT, it is important that any systematic review be comprehensive and that the meta-analysis accounts for inherent sources of heterogeneity as best as possible. Our work improves upon the previous published reviews that have significant limitations of methodology. For example, we have included studies that were excluded in other reports with narrower inclusion criteria, allowing for the ability to comment on important subgroups such as cardiac surgery patients.40,98,99,112 In addition, we avoided pooling complications as an artificial composite,98,102,113,114 mixing GDT trials with those exploring liberal versus restrictive fluid administration,102 and pooling both PAC-guided and contemporary GDT studies together.98,99,103 With reference to the latter, it was our opinion that certain PAC studies generally did not reflect contemporary practice and were of lower methodological quality, which would decrease the external validity of the results had they been pooled with the data from more contemporary trials.1
Despite the low statistical heterogeneity in our morbidity and mortality analyses, the main limitation of this meta-analysis is the clinical heterogeneity among the different GDT devices, goals and algorithms employed by included studies. Although such clinical heterogeneity can never be fully mitigated by statistical means, we took several measures to address this issue, such as the use of a random effects model, stratification of the results by PAC-guided GDT versus modern GDT, and finally subgroup analysis by other important sources of heterogeneity (e.g. type of GDT monitor).
Another important consideration is the comparability between different GDT devices; indeed, studies exploring the correlation between different GDT monitors for reflecting haemodynamic status have demonstrated mixed results.115–117 Significantly, in subgroup analysis by type of technology, the mortality benefit of modern GDT only persisted in the minimally invasive CO monitor subgroup, which reduces the ability to generalise the primary outcome results.
In addition, although our analysis identified several secondary benefits of peri-operative GDT, the secondary outcomes should be interpreted with caution because not all studies reported each outcome, and the timing of follow-up varied between studies. Furthermore, another significant limitation is the high risk of bias among included studies. For example, only four of 95 studies performed blinding and more than half of the studies had an unclear description of allocation concealment (Fig. 2). Regarding other sources of bias, study investigators had relationships with industry in 31 of 95 trials.10,12,13,16,24,27,29,30,36,37,40,45,47,48,51,59,63,64,66,68,76,77,80–82,84,88,91,92,94,114 Previous work has demonstrated that industry influence in a trial increases the chance that the results will favour the intervention.118 Therefore, we cannot exclude the effect that such heavy industry involvement may have increased the effect sizes observed here, which is compounded by the other deficiencies in methodology of the evidence base.118
In summary, this systematic review and meta-analysis of RCTs demonstrates reduced mortality, morbidity and hospital LoS with contemporary GDT in non-trauma and non-pregnant adult surgical patients. For every 1000 patients treated with modern GDT, 18 (95% CI, 7 to 26) deaths are prevented and organ-specific morbidity is reduced. Importantly, the benefits of GDT seem to be reliant on the use of vasoactive agents and the mortality results were not statistically significant in some important subgroups, such as cardiac surgery patients. Nonetheless, the results are relevant to anaesthetic practice; the performance of intra-operatively initiated GDT still yielded clinically important benefits. However, caution is warranted due to the significant flaws in the existing evidence base, the overall GRADE scoring of low to very low for the most important outcomes, and clinical heterogeneity among the haemodynamic goals and GDT monitoring devices studied.
Given the deficits in the current evidence base, it is fortunate that higher quality trials are currently in progress, such as the international OPTIMISE-II Study (http://optimiseii.org/). Large trials such as OPTIMISE-II are important for clarifying the magnitude of benefit of peri-operative GDT, particularly given the inconclusive TSA and the fact that the existing literature has a predominance of small trials (less than 100 patients). In addition, further study is required in clinically important subgroups, such as cardiac and emergency surgery patients. Finally, the best GDT protocols and haemodynamic targets still remain to be identified. Given the benefits found here and the potential for GDT to transform peri-operative anaesthetic care, this field will probably remain an active area of research.
Acknowledgements relating to this article
Assistance with the study: we thank fellow department members Dr Rudy Noppens (MD) and Dr Maurico Geraldo (MD) for their assistance in interpreting non-English language articles for this systematic review and meta-analysis. In addition, we are grateful for Brie McConnell's assistance in retrieving full-text copies of certain study articles.
Financial support and sponsorship: none.
Conflicts of interest: none.
Presentation: preliminary data from this review was presented as an oral presentation at the 2017 Canadian Anesthesiologists’ Society meeting in Niagara Falls, Ontario, Canada (24 to 26 June 2017).
1. Shoemaker WC, Appel PL, Kram HB, et al. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest
2. Cordero-Rochet MJ, McCluskey SA, Minkovich L, et al. Goal directed fluid management in free flap reconstructive surgery. Can J Anesth
3. Ziegler DW, Wright JG, Choban PS, et al. A prospective randomized trial of preoperative ‘optimization’ of cardiac function in patients undergoing elective peripheral vascular surgery. Surgery
4. Zheng H, Guo H, Ye JR, et al. Goal-directed fluid therapy in gastrointestinal surgery in older coronary heart disease patients: randomized trial. World J Surg
5. Zheng LS, Gu EW, Peng XH, et al. Effect of goal-directed haemodynamic management on the postoperative outcome in elderly patients with fragile cardiac function undergoing abdominal surgery. Zhonghua Yi Xue Za Zhi
2016; 96:3464–3469. Chinese.
6. Zhang J, Chen CQ, Lei XZ, et al. Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study. Clinics
7. Zhang J, Qiao H, He Z, et al. Intraoperative fluid management in open gastrointestinal surgery: goal-directed versus restrictive. Clinics
8. Zhang J, Shi QY, Luo AL. Influence of goal-directed fluid therapy during anaesthesia on the prognosis of patients undergoing craniotomy for resection of glioma. Br J Anaesth
9. Zeng K, Li Y, Liang M, et al. The influence of goal-directed fluid therapy on the prognosis of elderly patients with hypertension and gastric cancer surgery. Drug Des Dev Ther
10. Zakhaleva J, Tam J, Denoya PI, et al. The impact of intravenous fluid administration on complication rates in bowel surgery within an enhanced recovery protocol: a randomized controlled trial. Colorectal Dis
11. Yassen AM. Pressure versus volume indices to guide fluid infusion early after living donor liver transplantation: a prospective randomized controlled trial. Egypt J Anaesth
12. Wilson J, Woods I, Fawcett J, et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ
13. Wakeling HG, McFall MR, Jenkins CS, et al. Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. Br J Anaesth
14. Venn R, Steele A, Richardson P, et al. Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. Br J Anaesth
15. Vanakas T, Asouhidou I, Samaras A, et al. Implementation of goal-directed protocol in elderly patients undergoing femoral fracture repair. Eur J Anaesthesiol
16. Van Der Linden PJ, Dierick A, Wilmin S, et al. A randomized controlled trial comparing an intraoperative goal-directed strategy with routine clinical practice in patients undergoing peripheral arterial surgery. Eur J Anaesthesiol
17. Van DJ, McCorkell S, Williams A. Randomised controlled trial of extended postoperative goal-directed fluid therapy using oesophageal Doppler within an enhanced recovery programme for elective colorectal patients. Association of Coloproctology of Great Britain and Ireland Annual Meeting
18. Valentine RJ, Duke ML, Inman MH, et al. Effectiveness of pulmonary artery catheters in aortic surgery: a randomized trial. J Vasc Surg
19. Tolstova I, Yavorovskiy A, Akselrod B. Goal-directed fluid management during off-pump coronary artery bypass grafting: is it worth doing? J Cardiothorac Vasc Anesth
20. Szturz P, Kula R, Tichy J, et al. Individual goal-directed intraoperative fluid management of initially hypovolemic patients for elective major urological surgery. Bratisl Lek Listy
21. Srinivasa S, Singh P, Yu T, et al. Randomized clinical trial of goaldirected fluid therapy within an enhanced recovery protocol for elective colectomy. Dis Colon Rectum
22. Smetkin AA, Kirov MY, Kuzkov VV, et al. Single transpulmonary thermodilution and continuous monitoring of central venous oxygen saturation during off-pump coronary surgery. Acta Anaesthesiol Scand
23. Sinclair S, James S, Singer M. Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial. BMJ
24. Senagore AJ, Emery T, Luchtefeld M, et al. Fluid management for laparoscopic colectomy: a prospective, randomized assessment of goal-directed administration of balanced salt solution or hetastarch coupled with an enhanced recovery program. Dis Colon Rectum
25. Schultz R, Whitfield G, Lamura J, et al. The role of physiologic monitoring in patients with fractures of the hip. J Trauma
26. Schmid S, Kapfer B, Heim M, et al. Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial. Critical Care
27. Scheeren TW, Wiesenack C, Gerlach H, et al. Goal-directed intraoperative fluid therapy guided by stroke volume and its variation in high-risk surgical patients: a prospective randomized multicentre study. J Clin Monit Comput
28. 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
29. Salzwedel C, Puig J, Carstens A, et al. Perioperative goal-directed haemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multicenter, prospective, randomized study. Crit Care
30. Ramsingh DS, Sanghvi C, Gamboa J, et al. Outcome impact of goal directed fluid therapy during high risk abdominal surgery in low to moderate risk patients: a randomized controlled trial. J Clin Monit Comput
31. Polonen P, Ruokonen E, Hippelainen M, et al. A prospective, randomized study of goal-oriented haemodynamic therapy in cardiac surgical patients. Anesth Analg
32. Pillai P, McEleavy I, Gaughan M, et al. A double-blind randomized controlled clinical trial to assess the effect of Doppler optimized intraoperative fluid management on outcome following radical cystectomy. J Urol
33. Phan TD, D'Souza B, Rattray MJ, et al. 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. Anaesth Intensive Care
34. Pestana D, Espinosa E, Eden A, et al. Perioperative goal-directed haemodynamic optimization using noninvasive cardiac output monitoring in major abdominal surgery: a prospective, randomized, multicenter, pragmatic trial: POEMAS Study (PeriOperative goal-directed thErapy in Major Abdominal Surgery). Anesth Analg
35. Peng K, Li J, Cheng H, et al. Goal-directed fluid therapy based on stroke volume variations improves fluid management and gastrointestinal perfusion in patients undergoing major orthopedic surgery. Med Princ Pract
36. Pearse R, Dawson D, Fawcett J, et al. Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial (ISRCTN38797445). Crit Care
37. Pearse RM, Harrison DA, MacDonald N, et al. Effect of a perioperative, cardiac output-guided haemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA
2014; 311:2181–2190. [Erratum appears in JAMA. 2014 Oct 8;312(14):1473].
38. Parke RL, McGuinness SP, Gilder E, et al. A randomised feasibility study to assess a novel strategy to rationalise fluid in patients after cardiac surgery. Br J Anaesth
39. Park S, Kim H, Koo B. Effect of goal-directed fluid therapy using stroke volume variation in free flap reconstruction. Anesth Analg
2016; 122: S-302.
40. Osawa EA, Rhodes A, Landoni G, et al. Effect of perioperative goal-directed haemodynamic resuscitation therapy on outcomes following cardiac surgery: a randomized clinical trial and systematic review. Crit Care Med
41. Noblett SE, Snowden CP, Shenton BK, et al. Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg
42. Mythen MG, Webb AR. Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Arch Surg
43. Munoz CAF, Rojas JLT, Bermudez OIG. Intraoperative oesophageal doppler during emergency abdominal surgery. Br J Anaesth
44. Moppett IK, Rowlands M, Mannings A, et al. LiDCO-based fluid management in patients undergoing hip fracture surgery under spinal anaesthesia: a randomized trial and systematic review. Br J Anaesth
45. Mikor A, Trasy D, Nemeth MF, et al. Continuous central venous oxygen saturation assisted intraoperative haemodynamic management during major abdominal surgery: a randomized, controlled trial. BMC Anesthesiol
46. McKenny M, Conroy P, Wong A, et al. A randomised prospective trial of intra-operative oesophageal Doppler-guided fluid administration in major gynaecological surgery. Anaesthesia
47. McKendry M, McGloin H, Saberi D, et al. Randomised controlled trial assessing the impact of a nurse delivered, flow monitored protocol for optimisation of circulatory status after cardiac surgery. Br Med J
48. Mayer J, Boldt J, Mengistu AM, et al. Goal-directed intraoperative therapy based on autocalibrated arterial pressure waveform analysis reduces hospital stay in high-risk surgical patients: a randomized, controlled trial. Crit Care
49. Martini A, Menestrina N, Simion D, et al. Perioperative fluid administration in pancreatic surgery: Comparison of three regimens. Crit Care
50. Lopes MR, Oliveira MA, Pereira VO, et al. Goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery: a pilot randomized controlled trial. Crit Care
51. Lai CW, Starkie T, Creanor S, et al. Randomized controlled trial of stroke volume optimization during elective major abdominal surgery in patients stratified by aerobic fitness. Br J Anaesth
52. Kumar L, Kanneganti YS, Rajan S. Outcomes of implementation of enhanced goal directed therapy in high-risk patients undergoing abdominal surgery. Indian J Anaesth
53. Kumar L, Rajan S, Baalachandran R. Outcomes associated with stroke volume variation versus central venous pressure guided fluid replacements during major abdominal surgery. J Anaesthesiol Clin Pharmacol
54. Kulkarni R, Craske DA, Abdel-Galil K, et al. Haemodynamic optimisation in head and neck cancer surgery; Pilot randomised controlled trial of LiDCO rapid. Eur Arch Oto-Rhino-Laryngol
55. Khambalia H, Nirmalan M, Dellen D, et al. Supra-physiological haemodynamic optimisation improves short-term outcomes following simultaneous pancreas and kidney transplantation: a randomised clinical trial (NCT01619904). Transpl Int
56. Kellman S, Roberts JD, Chaney M, et al. Prospective randomized clinical trial comparing routine intraoperative transesophageal echocardiography to standard care during radical cystectomy. Anesth Analg
57. Kapoor PM, Kakani M, Chowdhury U, et al. Early goal-directed therapy in moderate to high-risk cardiac surgery patients. Ann Card Anaesth
58. Kapoor PM, Magoon R, Rawat R, et al. Perioperative utility of goal-directed therapy in high-risk cardiac patients undergoing coronary artery bypass grafting: ‘a clinical outcome and biomarker-based study’. Ann Card Anaesth
59. Jhanji S, Vivian-Smith A, Lucena-Amaro S, et al. Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial. Crit Care
60. Jerez Gomez-Coronado V, Robles MM, Perez CD, et al. Haemodynamic optimization and morbimortality after heart surgery. Med Intens
61. Jammer I, Tuovila M, Ulvik A. Stroke volume variation to guide fluid therapy: is it suitable for high-risk surgical patients? A terminated randomized controlled trial. Perioper Med
62. Han G, Liu K, Xue H, et al. Application of LiDCO-Rapid in peri-operative fluid therapy for aged patients undergoing total hip replacement. Int J Clin Exp Med
63. Hand WR, Stoll WD, McEvoy MD, et al. Intraoperative goal-directed haemodynamic management in free tissue transfer for head and neck cancer. Head Neck
2015; 38:E1974–E1980. 01.
64. Harten J, Crozier JE, McCreath B, et al. Effect of intraoperative fluid optimisation on renal function in patients undergoing emergency abdominal surgery: a randomised controlled pilot study (ISRCTN 11799696). Int J Surg
65. Hughes T, Cottam S, Heaton N, et al. Peri-operative haemodynamic optimisation using pulsioflex monitoring in whipples surgery. Anaesthesia
66. Goepfert MS, Richter HP, Zu Eulenburg C, et al. Individually optimized haemodynamic therapy reduces complications and length of stay in the intensive care unit: a prospective, randomized controlled trial. Anesthesiology
67. Gerent A, Almeida JP, Galas F, et al. Goal-directed therapy in cancer surgery: a randomised and controlled trial (GRICS II). Intensive Care Med Experimental
2015; 3 (Suppl 1):A819.
68. Gan TJ, Soppitt A, Maroof M, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology
69. Funk DJ, HayGlass KT, Koulack J, et al. A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair. Critical Care
70. Fellahi JL, Brossier D, Dechanet F, et al. Early goal-directed therapy based on endotracheal bioimpedance cardiography: a prospective, randomized controlled study in coronary surgery. J Clin Monit Comput
71. El Sharkawy OA, Refaat EK, Ibraheem AE, et al. Transoesophageal Doppler compared to central venous pressure for perioperative haemodynamic monitoring and fluid guidance in liver resection. Saudi J Anaesth
72. Donati A, Loggi S, Preiser JC, et al. Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients. Chest
73. Correa-Gallego C, Tan KS, Arslan-Carlon V, et al. Goal-directed fluid therapy using stroke volume variation for resuscitation after low central venous pressure-assisted liver resection: a randomized clinical trial. J Am Coll Surg
74. Conway DH, Mayall R, Abdul-Latif MS, et al. Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery. Anaesthesia
75. Colantonio L, Claroni C, Fabrizi L, et al. A randomized trial of goal directed vs. standard fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. J Gastrointest Surg
76. Challand C, Struthers R, Sneyd JR, et al. Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery. Br J Anaesth
77. Cecconi M, Fasano N, Langiano N, et al. Goal-directed haemodynamic therapy during elective total hip arthroplasty under regional anaesthesia. Crit Care
78. Calvo Vecino JM, Ripolles MJ, Martinez HE, et al. Efficacy of intraoperatory optimisation offluids guided with transoesophageal doppler monitorisation: A multicentre randomised controlled trial. Eur J Anaesthesiol
79. Bundgaard-Nielsen M, Jans O, Muller RG, et al. Does goal-directed fluid therapy affect postoperative orthostatic intolerance?: A randomized trial. Anesthesiology
80. Buettner M, Schummer W, Huettemann E, et al. Influence of systolic-pressure-variation-guided intraoperative fluid management on organ function and oxygen transport. Br J Anaesth
81. Broch O, Carstens A, Gruenewald M, et al. Noninvasive haemodynamic optimization in major abdominal surgery: a feasibility study. Minerva Anestesiol
82. Brandstrup B, Svendsen PE, Rasmussen M, et al. Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance? Br J Anaesth
83. Boyd O, Grounds RM, Bennett ED. A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients. JAMA
84. Ackland GL, Iqbal S, Paredes LG, et al. Individualised oxygen delivery targeted haemodynamic therapy in high-risk surgical patients: a multicentre, randomised, double-blind, controlled, mechanistic trial. Lancet Respir Med
85. Bartha E, Arfwedson C, Imnell A, et al. Randomized controlled trial of goal-directed haemodynamic treatment in patients with proximal femoral fracture. Br J Anaesth
86. Ben Romdhane M, Ben Souissi A, Nefzi I, et al. Perioperative haemodynamic optimization by oesophageal doppler monitoring in abdominal emergencies-preliminary results. Intensive Care Med
2014; S60 (Suppl 1):
87. Bender JS, Smith-Meek MA, Jones CE. Routine pulmonary artery catheterization does not reduce morbidity and mortality of elective vascular surgery: results of a prospective, randomized trial. Ann Surg
88. Benes J, Chytra I, Altmann P, et al. Intraoperative fluid optimization using stroke volume variation in high risk surgical patients: results of prospective randomized study. Crit Care
89. Benes J, Haidingerova L, Pouska J, et al. Fluid management guided by a continuous noninvasive arterial pressure device is associated with decreased postoperative morbidity after total knee and hip replacement. BMC Anesthesiol
90. Berlauk JF, Abrams JH, Gilmour IJ, et al. Preoperative optimization of cardiovascular haemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Ann Surg
1991; 214:289–297. Discussion 98–99.
91. Bisgaard J, Gilsaa T, Ronholm E, et al. Haemodynamic optimisation in lower limb arterial surgery: room for improvement? Acta Anaesthesiol Scand
92. Bisgaard J, Gilsaa T, Ronholm E, et al. Optimising stroke volume and oxygen delivery in abdominal aortic surgery: a randomised controlled trial. Acta Anaesthesiol Scand
93. Bonazzi M, Gentile F, Biasi GM, et al. Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. A randomised pilot trial. Eur J Vasc Endovasc Surg
94. Forget P, Lois F, De KM. Goal-directed fluid management based on the pulse oximeter-derived pleth variability index reduces lactate levels and improves fluid management. Anesth Analg
95. Oubaha D, Poelaert J. Does stroke volume variation guided fluid management improve postoperative outcome? Eur J Anaesthesiol
96. Abbas SM, Hill AG. Systematic review of the literature for the use of oesophageal Doppler monitor for fluid replacement in major abdominal surgery. Anaesthesia
97. Vincent JL, Rhodes A, Perel A, et al. Clinical review: update on haemodynamic monitoring – a consensus of 16. Crit Care
98. Arulkumaran N, Corredor C, Hamilton MA, et al. Cardiac complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis. Br J Anaesth
99. Corcoran T, Rhodes JE, Clarke S, et al. Perioperative fluid management strategies in major surgery: a stratified meta-analysis. Anesth Analg
100. Jia FJ, Yan QY, Sun Q, et al. Liberal versus restrictive fluid management in abdominal surgery: a meta-analysis. Surg Today
101. Schol PB, Terink IM, Lance MD, et al. Liberal or restrictive fluid management during elective surgery: a systematic review and meta-analysis. J Clin Anesth
102. Boland MR, Noorani A, Varty K, et al. Perioperative fluid restriction in major abdominal surgery: systematic review and meta-analysis of randomized, clinical trials. World J Surg
103. 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
104. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. J Clin Epidemiol
105. Corbett MS, Higgins JP, Woolacott NF. Assessing baseline imbalance in randomised trials: implications for the Cochrane risk of bias tool. Res Synth Methods
106. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ
107. Bangalore S, Toklu B, Wetterslev J. Complete versus culprit-only revascularization for ST-segment–elevation myocardial infarction and multivessel disease a meta-analysis and trial sequential analysis of randomized trials. Circulation
108. Thorlund K, Engstrøm J, Wetterslev J, et al. User manual for trial sequential analysis (TSA). 2011; Copenhagen, Denmark: Copenhagen Trial Unit, Centre for Clinical Intervention Research, 1–115.
109. Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA
110. American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Practice guidelines for pulmonary artery catheterization: an updated report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Anesthesiology
111. Checketts MR, Alladi R, Ferguson K, et al. Recommendations for standards of monitoring during anaesthesia and recovery 2015: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia
112. Rollins KE, Lobo DN. Intraoperative goal-directed fluid therapy in elective major abdominal surgery: a meta-analysis of randomized controlled trials. Ann Surg
113. Som A, Maitra S, Bhattacharjee S, et al. Goal directed fluid therapy decreases postoperative morbidity but not mortality in major noncardiac surgery: a meta-analysis and trial sequential analysis of randomized controlled trials. J Anesth
114. Benes J, Giglio M, Brienza N, et al. The effects of goal-directed fluid therapy based on dynamic parameters on postsurgical outcome: a meta-analysis of randomized controlled trials. Crit Care
115. Biais M, Nouette-Gaulain K, Roullet S, et al. A comparison of stroke volume variation measured by Vigileo/FloTrac system and aortic Doppler echocardiography. Anesth Analg
116. Lahner D, Kabon B, Marschalek C, et al. Evaluation of stroke volume variation obtained by arterial pulse contour analysis to predict fluid responsiveness intraoperatively. Br J Anaesth
117. Marquez J, McCurry K, Severyn DA, et al. Ability of pulse power, esophageal Doppler, and arterial pulse pressure to estimate rapid changes in stroke volume in humans. Crit Care Med
118. Bhandari M, Busse JW, Jackowski D, et al. Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials. CMAJ