- Open Access
Effect of perioperative goal-directed hemodynamic therapy on postoperative recovery following major abdominal surgery—a systematic review and meta-analysis of randomized controlled trials
Critical Care volume 21, Article number: 141 (2017)
Goal-directed hemodynamic therapy (GDHT) has been used in the clinical setting for years. However, the evidence for the beneficial effect of GDHT on postoperative recovery remains inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effect of perioperative GDHT in comparison with conventional fluid therapy on postoperative recovery in adults undergoing major abdominal surgery.
Randomized controlled trials (RCTs) in which researchers evaluated the effect of perioperative use of GDHT on postoperative recovery in comparison with conventional fluid therapy following abdominal surgery in adults (i.e., >16 years) were considered. The effect sizes with 95% CIs were calculated.
Forty-five eligible RCTs were included. Perioperative GDHT was associated with a significant reduction in short-term mortality (risk ratio [RR] 0.75, 95% CI 0.61–0.91, p = 0.004, I 2 = 0), long-term mortality (RR 0.80, 95% CI 0.64–0.99, p = 0.04, I 2 = 4%), and overall complication rates (RR 0.76, 95% CI 0.68–0.85, p < 0.0001, I 2 = 38%). GDHT also facilitated gastrointestinal function recovery, as demonstrated by shortening the time to first flatus by 0.4 days (95% CI −0.72 to −0.08, p = 0.01, I 2 = 74%) and the time to toleration of oral diet by 0.74 days (95% CI −1.44 to −0.03, p < 0.0001, I 2 = 92%).
This systematic review of available evidence suggests that the use of perioperative GDHT may facilitate recovery in patients undergoing major abdominal surgery.
Perioperative fluid management has been recognized as an important factor in postoperative recovery following major abdominal surgery [1, 2]. There is evidence that either too little or too much fluid administration during the perioperative period was associated with organ dysfunction, delayed gastrointestinal (GI) function, and increased complication rates after surgery . However, optimal fluid management is difficult to achieve using standard parameters (e.g., heart rate [HR], blood pressure [BP], central venous pressure [CVP], or urine output) that poorly estimate preload and preload responsiveness .
Goal-directed hemodynamic therapy (GDHT) was proposed by introducing different hemodynamic variables into a dynamic perspective of individual fluid loading with or without vasoactive substances to reach a predefined goal of optimal preload and/or oxygen delivery . An increasing numbers of studies of the effect of perioperative GDHT on postoperative recovery following major abdominal surgery are being done. However, the evidence for the beneficial effect of GDHT on postoperative recovery remains inconsistent. Several meta-analyses demonstrated that GDHT could decrease postoperative morbidity and mortality in patients undergoing major surgery [1, 6, 7], but others suggested that the treatment benefit may be more marginal than previously believed [8,9,10]. More recent studies [1, 11,12,13,14] have shown either equivalent or inferior outcomes in patients randomized to GDHT following major abdominal surgery. Therefore, we performed this up-to-date systematic review and meta-analysis to evaluate all available evidence regarding the effect of preoperative GDHT in comparison with conventional fluid therapy on postoperative recovery in adults undergoing major abdominal surgery.
We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in reporting this systematic review and meta-analysis . A review protocol was written before this study was conducted.
Inclusion and exclusion criteria
The eligible studies of this systematic review and meta-analyses were identified using the patient, intervention, comparison, outcomes, study design strategy :
Patients/participants: Adult patients (aged ≥16 years) undergoing major abdominal surgery were evaluated. Major abdominal surgery was defined using the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity . Studies involving pediatric patients, nonsurgical patients, or postoperative patients with already-established sepsis or organ failure and undergoing late optimization were excluded.
Type of intervention: Preoperative GDHT was used as the intervention treatment, which was defined as preoperative administration of fluids (initiated before surgery or in the intraoperative period and maintained in the postoperative period, or performed in the immediate postoperative period and lasting up to 6 h after surgery), with or without inotropes/vasoactive drugs, to increase blood flow (relative to control) against explicit measured goals, defined as cardiac output (CO), cardiac index, oxygen delivery (DO2), oxygen delivery index (DO2I), oxygen consumption, stroke volume (SV), dynamic measures of preload responsiveness (e.g., stroke volume variation [SVV], pulse pressure variation [PPV], and pleth variability index [PVI]), mixed venous oxygen saturation, oxygen extraction ratio, or lactate. Studies in which GDHT was limited to the preoperative period were excluded.
Type of comparator: Conventional fluid administration strategies were used as control group, defined as that using the standard monitoring parameters (BP, HR, urine output, and CVP) to guide fluid therapy.
Types of outcomes: Studies in which researchers reported postoperative complications, mortality, and GI function recovery outcomes (i.e., time to tolerate oral diet, time to first flatus, and time to first bowel movement) were included.
Types of studies: Randomized controlled trials (RCTs), with or without blinding, were included. Data derived from letters, case reports, reviews, or cohort studies were excluded.
Search strategy and study selection
A systematic search of MEDLINE, Embase, CINAHL, Scopus, the Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews from inception to November 2016 was performed to identify relevant studies using the following search terms: “surgery,” “fluid,” “goal directed,” “end point,” “hemodynamic,” “target,” “goal,” and “randomized controlled trials.” Detailed search information used in MEDLINE is presented in Appendix 1. No language restriction was placed on our search. Ongoing trials were searched in the ClinicalTrials.gov databased as well as in conference abstracts, which might provide results even though the trials have not been published yet. Furthermore, the reference lists of the identified reports, reviews, and other relevant publications were reviewed to find additional relevant trials. The reference lists of all eligible publications and reviews were scanned to identify additional studies. Two authors (YS and FC) independently screened and reviewed all titles and abstracts for eligibility. For abstracts that did not provide sufficient information to determine eligibility, full-length articles were retrieved. Agreement between the two authors for inclusion of screened articles was measured using weighted kappa, and disagreement on inclusion or exclusion of articles was resolved by consensus.
Studies were reviewed and data were extracted independently by two authors (YS and FC) using a predesigned standard form, with any discrepancy being resolved by reinspection of the original article. The following data points were extracted: first author, year of publication, total number of patients, patients’ characteristics, abdominal procedures, the GDHT strategy (goals, monitoring methods, and interventions). The primary endpoints of this review included long-term mortality (i.e., death in longest available follow-up), short-term mortality (i.e., death in the hospital or within 30 days after surgery), and overall complication rates (i.e., number of patients with complications after surgery). The secondary outcome was recovery of GI function, including time to toleration of an oral diet, time to first flatus, and time to first bowel movement. Authors were contacted for missing information about fluid management or data on postoperative recovery. If detailed information was not received, data from such studies were excluded from the present meta-analysis.
The Cochrane Collaboration’s tool  for assessing risk of bias was applied independently by two authors. Risk of bias was assessed as high, low, or unclear for each of selection bias, performance bias, detection bias, attrition bias, and reporting bias. Information for judging the risk of bias was collected from all reports originating from one study, as well as from the protocol published in the registry, if applicable. Appropriate allocation to group assignment and concealment of randomization were considered more important than other domains for minimizing risk of bias in evaluating the effect of GDHT on postoperative recovery after major abdominal surgery, and the reviewers gave more importance to these domains when deciding on overall risk of bias. Agreement between the two reviewers on overall risk-of-bias assessment was determined using weighted kappa as well. Disagreements were resolved through discussion.
Grading quality of evidence
The quality of evidence for each outcome was assessed according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods for risk of bias, inconsistency, indirectness, imprecision, and publication bias, and it was evaluated using GRADEPro software 3.6 (GRADE Working Group). These were classified as very low, low, moderate, or high [19, 20].
All statistical analyses were conducted using RevMan 5.1 (The Cochrane Collaboration, Oxford, UK) and Stata/SE software 10.0 (StataCorp, College Station, TX, USA). Meta-analysis was undertaken where data were sufficient. For continuous data, weighted mean differences (WMDs) with 95% CIs were calculated. If the 95% CI included 0, the difference between the GDHT and control groups was not considered statistically significant. When mean and SD values were not given, they were estimated from the median and SE or CI or from the IQR using the method described by Hozo et al. . Dichotomous data were analyzed by use of risk ratio (RR) with 95% CI. If the 95% CI around the RR did not include 1.0, the difference between the GDHT and control groups was assumed to be statistically significant. We assessed the included studies for functional equivalence, but we additionally used the Cochran chi-square Q and I 2 statistics to assess heterogeneity across studies. Heterogeneity was considered as either a p value <0.05 or I 2 > 25% . The use of either a fixed-effect or random-effect model was based on a combination of these methods.
The univariate meta-regression analyses were conducted when appropriate (i.e., number of studies >10) to explore the potential heterogeneity according to type of monitoring technology, type of interventions, therapeutic goals, whether in context with enhanced recovery programs, and overall “fitness” of the patients (i.e., high- risk patients versus non-high-risk patients). High-risk patients were defined as patients with an American Society of Anesthesiologists physical status classification of III with two or more risk factors according to the risk index of Lee (i.e., high-risk type of surgery, ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, insulin therapy for diabetes, and preoperative serum creatinine >2.0 mg/dl) . Moreover, prespecified subgroup analyses were conducted on the basis of these potential confounders to minimize heterogeneity and evaluate the effect of GDHT in the specific subpopulations. Additional sensitivity analyses were performed, including studies for colorectal surgical procedures, studies randomizing large-sample-size patients (defined as sample size ≥100), and studies judged to carry a low risk of bias. Finally, the influence of each study was evaluated on the basis of overall estimates by calculating random-effect pooled estimates, omitting each estimate one at a time .
There were 12,348 records for title and abstract screening. After applying inclusion and exclusion criteria, 12,188 citations were excluded because of duplication of published data, not reporting original research, or no human patients being involved. The remaining subset of 160 articles was gathered for further review. This group was evaluated in detail by each author to reach consensus on whether the articles met the inclusion criteria described above until full consensus was reached. Of this group, 115 articles were excluded because they were not RCTs, involved nonsurgical patients, did not evaluate the effect of GDHT, did not involve major abdominal surgery, did not use conventional fluid therapy as a control group, or were published only in letter or abstract form. A total of 45 RCTs were finally considered for this review (Fig. 1). The authors had perfect agreement in selecting the 45 studies using the stated eligibility criteria.
The 45 RCTs [1, 11,12,13,14, 26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65] yielded 6344 patients (Table 1). Of those patients, 3406 received perioperative GDHT. Sample sizes ranged from 27 to 1994. All studies were reported between 1988 and 2015 in English-language journals.
Bias risk was analyzed with the Cochrane tool. The methodological quality of included trials is presented in a summary graph (Fig. 2) and table (Additional file 1). A total of 26 studies (58%) [1, 3, 11,12,13, 27, 28, 31, 32, 36,37,38, 40, 43, 45,46,47, 50, 51, 57,58,59, 61, 62, 64, 65] were judged to carry a low risk of bias (Table 1). Weighted kappa was calculated to examine agreement for each component and overall risk of bias assessment. The kappa statistics showed substantial agreement between the reviewers (Additional file 2).
Eight trials [26, 29, 30, 46, 50, 53, 54, 56] used pulmonary arterial catheters for monitoring; fourteen trials [3, 11, 14, 32, 33, 36, 42, 44, 48, 49, 51, 55, 62, 64] used esophageal Doppler monitoring; fifteen trials [3, 12, 27, 28, 31, 38, 39, 41, 43, 45, 52, 59,60,61, 65] used self-calibrating/calibrated pulse contour analysis monitoring; and the remaining eight trials used other monitors, including arterial lines plus monitoring equipment , central lines and arterial line sampling [34, 37, 57], pulse oximeters [35, 58], and other noninvasive monitors [13, 47]. Three types of goals were used in the majority of included trials, including DO2I and/or cardiac index [13, 26, 29, 30, 43, 46, 50, 53, 54, 56, 59], optimal SV [1, 11, 28, 32, 33, 36, 38, 39, 42, 44, 48, 49, 51, 55], and dynamic measures of preload responsiveness (e.g., PPV, SVV, PVI) [12, 27, 31, 35, 40, 41, 45, 52, 58, 60, 61, 65].
Thirty-three trials [1, 11, 14, 26,27,28,29,30,31,32,33,34,35,36, 38,39,40,41,42,43, 46, 48, 50, 52, 53, 56, 57, 60, 62, 64, 65] provided data on long-term mortality, and further information was obtained from a previous meta-analysis  for one study . The long-term mortality was 242 (8.1%) of 2959 in the GDHT group and 285 (9.9%) of 2888 in the control group, and the pooled RR of 0.80 showed that use of perioperative GDHT was barely associated with improved long-term survival after major abdominal surgery compared with the control group (95% CI 0.64–99, p = 0.04; I 2 = 4%) (Fig. 3a). The GRADE quality of evidence was judged to be moderate, downgraded for risk of bias.
Subgroup analyses revealed that a statistically significant effect of GDHT in long-term mortality for high-risk patients (RR 0.57, 95% CI 0.36–0.89, p = 0.01; I 2 = 51%; number of studies [n] = 12 [1, 27, 30, 32, 34, 36, 41, 43, 46, 50, 56, 65]), patients using cardiac index and/or DO2I as therapeutic goals (RR 0.48, 95% CI 0.25–0.94, p = 0.03; I 2 = 60%; n = 9 [13, 26, 29, 30, 43, 46, 50, 53, 56]), and patients using fluids and inotropes as interventions (RR 0.63, 95% CI 0.44–0.89, p = 0.008; I 2 = 32%; n =20 [1, 12, 13, 26,27,28,29,30, 34, 38, 40, 41, 43, 46, 50, 53, 56, 57, 60, 65]) (Additional file 3). Meta-regression analyses did not find the significant effect of overall “fitness” of the patients, type of monitoring technology, type of intervention, therapeutic goals, and whether in context with enhanced recovery programs on our result (Additional file 4). No statistical difference was found when we analyzed studies for colorectal surgical procedures, studies randomizing large-sample-size patients, and studies carrying a low risk of bias (Additional file 3). The influence analyses showed that each study except one trial  had a minor influence on the overall pooled RR. The statistical difference between the GDHT and control groups reached significance after this trial was omitted (RR 0.63, 95% CI 0.48–0.83, p = 0.001) (Fig. 3b). Neither Begg’s adjusted rank correlation test (p = 0.10) nor Egger’s regression asymmetry test (p = 0.93) was significant for mortality. A funnel plot is presented in Additional file 5.
Thirty-four studies [1, 11,12,13,14, 26,27,28,29,30,31,32,33,34,35,36, 38,39,40,41, 43, 44, 46,47,48, 50, 52,53,54, 56, 60, 62, 64, 65] provided suitable data for analysis. The pooled short-term mortality was 153 (5.2%) of 2959 in the GDHT group and 203 (7.0%) of 2888 in the control group, and the RR was 0.75 (95% CI 0.61–0.91, p = 0.004; I 2 = 0%), showing a significant reduction in the GDHT group (Fig. 4a). The GRADE quality of evidence was judged to be moderate, downgraded for risk of bias.
In subgroup analyses, we found that GDHT significantly reduced short-term mortality when a pulmonary arterial catheter was used for monitoring (RR 0.36, 95% CI 0.14–0.96, p = 0.04; I 2 = 68%; n = 7 [26, 29, 30, 46, 50, 53, 56]), cardiac index and/or DO2I were used as therapeutic goals 2(RR 0.49, 95% CI 0.25–0.94, p = 0.03; I 2 = 55%; n = 9 [13, 26, 29, 30, 43, 46, 50, 53, 56]), fluids and inotropes were used as interventions (RR 0.65, 95% CI 0.47–0.89, p = 0.007; I 2 =19%; n = 20 [1, 12, 13, 26,27,28,29,30, 34, 38, 40, 41, 43, 46, 50, 53, 56, 57, 60, 65]), outside of enhanced recovery programs (RR 0.71, 95% CI 0.53–0.94, p < 0.0001; I 2 = 11%; n = 25 [1, 12, 26,27,28, 31, 33,34,35, 38, 40, 41, 43]), and for high-risk patients (RR 0.73, 95% CI 0.58–0.91, p = 0.09; I 2 = 39%; n = 12 [1, 27, 30, 32, 34, 36, 41, 43, 46, 50, 56, 65]) (Additional file 3). Again, meta-regression analysis failed to identify the significant factors contributing this result (Additional file 6). No statistical difference was found when we analyzed studies for colorectal surgical procedures, studies randomizing large-sample-size patients, and studies carrying a low risk of bias (Additional file 3). The influence analyses showed each study had no substantial influence on the overall pooled RR (Fig. 4b). A funnel plot is presented in Additional file 7. Neither Begg’s adjusted rank correlation test (p = 0.08) nor Egger’s regression asymmetry test (p = 0.48) showed evidence of publication bias regarding short-term mortality.
Overall complication rates
Thirty-one trials [11,12,13, 26,27,28, 32,33,34, 36,37,38,39, 41,42,43, 47, 49, 50, 53,54,55,56,57, 61, 62, 64, 65] reported suitable data on number of patients with complications. The pooled RR of 0.76 showed reduced overall complication rates after major abdominal surgery in the GDHT group compared with the control group (95% CI 0.68–0.85, p < 0.0001; I 2 = 38%) (Fig. 5a). The GRADE quality of evidence was judged to be low, downgraded for risk of bias and inconsistency.
Subgroup analyses showed a significant reduction in GDHT group in those studies using pulse contour analysis monitoring (RR 0.75, 95% CI 0.64–0.87, p = 0.003; I 2 = 33%; n = 10 [1, 12, 27, 28, 38, 39, 41, 43, 61, 65]), using esophageal Doppler monitoring (RR 0.75, 95% CI 0.58–0.95, p = 0.002; I 2 = 53%; n = 10 [11, 14, 32, 33, 36, 42, 51, 55, 62, 64]), using fluids and inotropes as interventions (RR 0.76, 95% CI 0.66–0.86, p < 0.0001; I 2 = 36%; n = 19 [1, 12, 13, 26,27,28, 34, 38, 40, 41, 43, 50]), using cardiac index and/or DO2I (RR 0.78, 95% CI 0.63–0.97, p = 0.03; I 2 = 18%; n = 7 [1, 26, 43, 53, 54, 56]), or optimal SV (RR 0.80, 95% CI 0.69–0.93, p = 0.0002; I 2 = 40%; n = 14 [1, 10, 11, 14, 28, 32, 33, 36, 38, 39, 42, 55, 62, 64]) or dynamic measures of preload responsiveness (RR 0.64, 95% CI 0.52–0.79, p < 0.0001; I 2 = 16%; n = 6 [12, 27, 40, 41, 61, 65]) as therapeutic goals, as well as for either high-risk patients (RR 0.65, 95% CI 0.56–0.76, p < 0.0001, I 2 = 28%; n = 10 [1, 27, 32, 34, 36, 41, 43, 50, 56, 65]) or non-high-risk patients (RR 0.84, 95% CI 0.74–0.96, p = 0.08; I 2 = 29%; n = 21 [11,12,13,14, 26, 28, 33, 37,38,39,40, 42, 47, 51, 53,54,55, 57, 61, 62, 64]) (Additional file 3). Meta-regression analyses did not reveal a significant effect of all predefined confounders on overall complication rates (Additional file 8). Additionally, a statistically significant effect of GDHT on overall complication rates was found when we pooled all studies carrying to a low risk of bias (RR 0.78, 95% CI 0.70–0.87, p < 0.0001; I 2 = 31% ; n = 20 [1, 11,12,13, 27, 28, 32, 36,37,38, 40, 43, 47, 50, 51, 57, 61, 62, 64, 65]) and studies randomizing large-sample-size patients (RR 0.79, 95% CI 0.69–0.89, p = 0.002; I 2 = 43% ; n = 19 [1, 11,12,13,14, 26, 27, 32, 34, 36,37,38, 42, 43, 54,55,56,57, 62]) (Additional file 3). The influence analyses showed each study had no substantial influence on the overall pooled RR (Fig. 5b). Begg’s test and Egger’s test excluded the presence of publication bias (p = 0.08 and p = 0.06, respectively). A funnel plot is presented in Additional file 9.
GI function recovery
Perioperative GDHT shortened the time to first flatus (WMD −0.40 days, 95% CI −0.72 to −0.08, p < 0.0001; I 2 = 74%; n = 10 [13, 32, 42, 44, 55, 58,59,60,61, 64]) and time to toleration of an oral diet (WMD −0.74 days, 95% CI −1.44 to −0.03, p < 0.0001; I 2 = 92%; n = 9 [32, 36, 42, 44, 45, 55, 59, 62, 64]), but it did not shorten the time to first bowel movement (Fig. 6). The GRADE quality of evidence was judged to be low, downgraded by risk of bias and inconsistency.
Subgroup analyses based on the type of monitoring and therapeutic goals were not performed, owing to the limited number of studies. A statistically significant effect of GDHT was observed on time to toleration of an oral diet when we pooled studies for non-high-risk patients (WMD −0.83 days, 95% CI −1.51 to −0.14, p = 0.03; I 2 = 59%; n = 6 [42, 44, 45, 55, 62, 64]) and on time to first flatus pass for non-high-risk patients (WMD −0.41 days, 95% CI −0.80 to −0.01, p = 0.04; I 2 = 71%; n = 8 [13, 42, 44, 55, 58, 60, 61, 64]) and patients using fluids and inotropes as interventions (WMD −0.45 days, 95% CI −0.83 to −0.06, p < 0.0001; I 2 = 64%; n = 4 [13, 59,60,61]). No significant difference between the GDHT and control groups was found by sensitivity analysis restricting studies for colorectal surgical procedures, studies randomizing large-sample-size patients, and studies carrying a low risk of bias. The influence analyses showed that each study had no substantial influence on the overall pooled estimates, except for one trial regarding the time to first bowel movement. After we omitted this study, the difference in the time to first bowel movement reached statistical significance (WMD −0.28 days, 95% CI −0.43 to −0.13, p = 0.01) (Fig. 6).
Begg’s test and Egger’s test revealed no evidence of publication bias regarding time to first flatus (p = 1.00 and p = 0.48, respectively), time to first bowel movement (p = 0.91 and p = 0.19, respectively), or time to toleration of an oral diet (p = 0.28 and p = 0.46, respectively). A funnel plot is presented in Additional file 10.
In this systematic review and meta-analysis, we found that perioperative GDHT improved survival, reduced overall complication rates, and facilitated GI functional recovery as demonstrated by shortening the time to first flatus pass and the time to toleration of an oral diet compared with conventional fluid therapy when all studies were considered. However, we did not identify the beneficial effects of GDHT on mortality and GI function when we restricted the analysis to higher-quality and large-sample-size studies; thus, future studies should be adequately powered and methodologically rigorous enough to confirm a clinically relevant effect in this area.
GDHT is currently recommended in the context of enhanced recovery programs, especially for moderate- to high-risk patients . High-risk patients tend to have an increased stress response to surgical aggression, increased oxygen demand, and reduced physiological reserves to deal with the metabolic requirements of the perioperative period. Strategies to maintain DO2 and minimize splanchnic hypoperfusion have been advocated to improve postoperative morbidity for high-risk surgical patients . In our subgroup analyses, we identified high-risk patients as a group that may potentially benefit from GDHT. However, the results of our subgroup analysis indicated that GDHT is beneficial mainly when used outside enhanced recovery programs. The potential explanation is that enhanced recovery programs emphasize the avoidance of bowel preparation, minimize fasting, and use preoperative carbohydrate loading . As a result, patients are less likely to be fluid-depleted during surgery and thus may not benefit as much from targeted fluid administration.
Many different GDHT strategies have been studied in the clinical setting. However, there is no clear consensus about the most effective or the most appropriate method of monitoring. One would suggest that the use of CO monitoring to guide administration of intravenous fluids coupled with inotropic drugs as part of a hemodynamic therapy algorithm, which has been shown to modify inflammatory pathways and improve tissue perfusion and oxygenation . In our subgroup analysis, we found that GDHT using cardiac index/DO2I as goals and using fluids and inotropes as interventions was associated with reductions in mortality and morbidity following major abdominal surgery. However, the meta-regression analyses did not reveal any significant effect of those confounders contributing to overall results regarding mortality and morbidity after major abdominal surgery. Therefore, future studies are needed to provide evidence supporting various goals and methods of monitoring.
With a number of recently published trials on this topic, this report is the most up-to-date analysis of the effects of GDHT on recovery after major abdominal surgery and is based on a comprehensive search strategy. This systematic review included eight high-quality studies [28, 37, 38, 43, 46, 50, 57, 58] that were not identified in the most recently published meta-analysis , as well as two newly published studies [1, 12]. Moreover, we also included 12 studies [26, 30, 34, 39, 41, 47,48,49, 52,53,54, 56] that were excluded from the previous meta-analyses. Our findings support results of previous meta-analyses either for all types of surgery  or following major abdominal surgery .
There are some notable limitations of this review; therefore, the results should be interpreted with caution. Although our systematic review was focused on major abdominal procedures, owing to the unique nature of physiological change, we tried to attenuate the divergent effects of a heterogeneous population . However, the risk-benefit balance may be varied between the surgical procedures on the basis of the degree and duration of physiological stress. First, the results of sensitivity analysis restricted to studies with colorectal surgical procedures did not show the positive effect of GDHT on mortality, morbidity, and GI function recovery. Second, the GDHT strategy is quite complex and varied between trials, including fluid management, monitoring methods, therapeutic goals, and perioperative care environment. None of the included studies mentioned evaluating the effect of a single, clearly defined intervention, and analyzing data from some of the included trials using potential “nonoptimal” regimens might have impacted the results of our meta-analysis. Although our meta-regression analysis did not reveal a statistically significant influence of those confounders on overall results, the possibility of the regimen of GDHT that may be efficacious for postoperative recovery could not be excluded. Third, the quality of outcome data reported in the included studies was variable. Although the subgroup and sensitivity analyses could reduce the heterogeneity, not all planned subgroup and sensitivity analyses could be performed, owing to insufficient suitable data reported. Thus, the observed statistical heterogeneity in certain analyses could not always be ensured. Moreover, outcome measures were not consistent across all studies, and only relevant data from included trials could be considered for meta-analysis because of the limitation of pooled analysis. Although return of GI function is considered a meaningful outcome following abdominal surgery, only 13 of the 45 included trials provided data on this outcome. In addition, a specific analysis of complications was not performed, owing to the varied definitions between studies. Fourth, about half of the included studies had small sample sizes (<100), which may lack statistical power to detect a clinically important difference in mortality. The sensitivity analysis when we restricted it to studies with higher methodological quality and studies with larger sample size did not confirm the results obtained. Finally, as with any meta-analysis, publication bias could not be excluded. Although Begg’s test and Egger’s test were conducted in this analysis and the results indicated no significant evidence for publication bias for each outcome, absence of significant asymmetry does not mean that publication bias was absent .
This systematic review of available evidence suggests that the use of perioperative GDHT could improve postoperative recovery following major abdominal surgery, as demonstrated by a reduction of postoperative morbidity, improvement of survival, and earlier return of GI function. However, the most effective GDHT strategy remains unclear, and future adequately powered, high-quality RCTs are therefore needed to address this issue.
Central venous pressure
- DO2 :
Oxygen delivery index
Enhanced recovery protocol
Corrected flow time
Goal-directed hemodynamic therapy
Grading of Recommendations, Assessment, Development and Evaluations
Intrathoracic blood volume index
Mean arterial pressure
Oxygen extraction ratio
Pulmonary arterial catheter
Pulmonary arterial occlusion pressure
Pulmonary arterial wedge pressure
Pulmonary capillary wedge pressure
Pulse pressure variation
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Pleth variability index
Randomized controlled trial
Systolic pressure variation
- StO2 :
Tissue blood oxygen saturation
Stroke volume index
Systemic vascular resistance
Stroke volume variation
- VO2 :
Weighted mean difference
Pearse RM, Harrison DA, MacDonald N, Gillies MA, Blunt M, Ackland G, 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;311:2181–90. A published erratum appears in JAMA. 2014;312:1473.
Gupta R, Gan TJ. Peri-operative fluid management to enhance recovery. Anaesthesia. 2016;71 Suppl 1:40–5.
Bundgaard-Nielsen M, Holte K, Secher NH, Kehlet H. Monitoring of peri-operative fluid administration by individualized goal-directed therapy. Acta Anaesthesiol Scand. 2007;51:331–40.
Meregalli A, Oliveira RP, Friedman G. Occult hypoperfusion is associated with increased mortality in hemodynamically stable, high-risk, surgical patients. Crit Care. 2004;8:R60–5.
Tote SP, Grounds RM. Performing perioperative optimization of the high-risk surgical patient. Br J Anaesth. 2006;97:4–11.
Ripollés-Melchor J, Espinosa Á, Martínez-Hurtado E, Abad-Gurumeta A, Casans-Francés R, Fernández-Pérez C, et al. Perioperative goal-directed hemodynamic therapy in noncardiac surgery: a systematic review and meta-analysis. J Clin Anesth. 2016;28:105–15.
Hamilton MA, Cecconi M, Rhodes A. A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients. Anesth Analg. 2011;112:1392–402.
Grocott MP, Dushianthan A, Hamilton MA, Mythen MG, Harrison D, Rowan K. Optimisation Systematic Review Steering Group. Perioperative increase in global blood flow to explicit defined goals and outcomes following surgery. Cochrane Database Syst Rev. 2012;11:CD004082.
Moppett IK, Rowlands M, Mannings A, Moran CG, Wiles MD. NOTTS Investigators. LiDCO-based fluid management in patients undergoing hip fracture surgery under spinal anaesthesia: a randomized trial and systematic review. Br J Anaesth. 2015;114:444–59.
Srinivasa S, Lemanu DP, Singh PP, Taylor MH, Hill AG. Systematic review and meta-analysis of oesophageal Doppler-guided fluid management in colorectal surgery. Br J Surg. 2013;100:1701–8.
Brandstrup B, Svendsen PE, Rasmussen M, Belhage B, Rodt SÅ, Hansen B, 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. 2012;109:191–9.
Correa-Gallego C, Tan KS, Arslan-Carlon V, Gonen M, Denis SC, Langdon-Embry L, 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. 2015;221:591–601.
Pestaña D, Espinosa E, Eden, Nájera D, Collar L, Aldecoa C, A et al. Perioperative goal-directed hemodynamic 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. 2014;119:579–87.
Phan TD, D’Souza B, Rattray MJ, Johnston MJ, Cowie BS. 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. 2014;42:752–60.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–12.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
Bar-Yosef S, Melamed R, Page GG, Shakhar G, Shakhar K, Ben-Eliyahu S. Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats. Anesthesiology. 2001;94:1066–73.
Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (Updated March 2011). The Cochrane Collaboration; 2011.
Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011.
Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401–6.
Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.
Tobías A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull. 1999;8(47):15–7.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.
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. 1997;226:229–37.
Benes J, Chytra I, Altmann P, Hluchy M, Kasal E, Svitak R, et al. Intraoperative fluid optimization using stroke volume variation in high risk surgical patients: results of prospective randomized study. Crit Care. 2010;14:R118.
Bisgaard J, Gilsaa T, Rønholm E, Toft P. Optimising stroke volume and oxygen delivery in abdominal aortic surgery: a randomised controlled trial. Acta Anaesthesiol Scand. 2013;57:178–88.
Bonazzi M, Gentile F, Biasi GM, Migliavacca S, Esposti D, Cipolla M, 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. 2002;23:445–51.
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. 1993;270:2699–707.
Buettner M, Schummer W, Huettemann E, Schenke S, van Hout N, Sakka SG. Influence of systolic-pressure-variation-guided intraoperative fluid management on organ function and oxygen transport. Br J Anaesth. 2008;101:194–9.
Challand C, Struthers R, Sneyd JR, Erasmus PD, Mellor N, Hosie KB, et al. Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery. Br J Anaesth. 2012;108:53–62.
Conway DH, Mayall R, Abdul-Latif MS, Gilligan S, Tackaberry C. Randomised controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery. Anaesthesia. 2002;57:845–9.
Donati A, Loggi S, Preiser JC, Orsetti G, Münch C, Gabbanelli V, et al. Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients. Chest. 2007;132:1817–24.
Forget P, Lois F, de Kock M. Goal-directed fluid management based on the pulse oximeter-derived pleth variability index reduces lactate levels and improves fluid management. Anesth Analg. 2010;111:910–4.
Gan TJ, Soppitt A, Maroof M, el-Moalem H, Robertson KM, Moretti E, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology. 2002;97:820–6.
Jammer I, Ulvik A, Erichsen C, Lødemel O, Ostgaard G. Does central venous oxygen saturation-directed fluid therapy affect postoperative morbidity after colorectal surgery? A randomized assessor-blinded controlled trial. Anesthesiology. 2010;113:1072–80.
Jhanji S, Vivian-Smith A, Lucena-Amaro S, Watson D, Hinds CJ, Pearse RM. Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial. Crit Care. 2010;14:R151.
Jones C, Kelliher L, Dickinson M, Riga A, Worthington T, Scott MJ, et al. Randomized clinical trial on enhanced recovery versus standard care following open liver resection. Br J Surg. 2013;100:1015–24.
Lopes MR, Oliveira MA, Pereira VO, Lemos IP, Auler Jr JO, Michard F. Goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery: a pilot randomized controlled trial. Crit Care. 2007;11:R100.
Mayer J, Boldt J, Mengistu AM, Röhm KD, Suttner S. 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. 2010;14:R18.
Noblett SE, Snowden CP, Shenton BK, Horgan AF. Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg. 2006;93:1069–76.
Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED. Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445]. Crit Care. 2005;9:R687–93.
Pillai P, McEleavy I, Gaughan M, Snowden C, Nesbitt I, Durkan G, 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. 2011;186:2201–6.
Ramsingh DS, Sanghvi C, Gamboa J, Cannesson M, Applegate 2nd RL. 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. 2013;27:249–57.
Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, 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.
Cohn SM, Pearl RG, Acosta SM, Nowlin MU, Hernandez A, Guta C, et al. A prospective randomized pilot study of near-infrared spectroscopy-directed restricted fluid therapy versus standard fluid therapy in patients undergoing elective colorectal surgery. Am Surg. 2010;76:1384–92.
Senagore AJ, Emery T, Luchtefeld M, Kim D, Dujovny N, Hoedema R. 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. 2009;52:1935–40.
El Sharkawy OA, Refaat EK, Ibraheem AE, Mahdy WR, Fayed NA, Mourad WS, et al. Transoesophageal Doppler compared to central venous pressure for perioperative hemodynamic monitoring and fluid guidance in liver resection. Saudi J Anaesth. 2013;7:378–86. A published erratum appears in Saudi J Anaesth. 2014;8:133.
Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest. 1988;94:1176–86.
Srinivasa S, Taylor MH, Singh PP, Yu TC, Soop M, Hill AG. Randomized clinical trial of goal-directed fluid therapy within an enhanced recovery protocol for elective colectomy. Br J Surg. 2013;100:66–74.
Szakmany T, Toth I, Kovacs Z, Leiner T, Mikor A, Koszegi T, et al. Effects of volumetric vs. pressure-guided fluid therapy on postoperative inflammatory response: a prospective, randomized clinical trial. Intensive Care Med. 2005;31:656–63.
Ueno S, Tanabe G, Yamada H, Kusano C, Yoshidome S, Nuruki K, et al. Response of patients with cirrhosis who have undergone partial hepatectomy to treatment aimed at achieving supranormal oxygen delivery and consumption. Surgery. 1998;123:278–86.
Valentine RJ, Duke ML, Inman MH, Grayburn PA, Hagino RT, Kakish HB, et al. Effectiveness of pulmonary artery catheters in aortic surgery: a randomized trial. J Vasc Surg. 1998;27:203–12.
Wakeling HG, McFall MR, Jenkins CS, Woods WG, Miles WF, Barclay GR, et al. Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. Br J Anaesth. 2005;95:634–42.
Wilson J, Woods I, Fawcett J, Whall R, Dibb W, Morris C, et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ. 1999;318:1099–103.
Wenkui Y, Ning L, Jianfeng G, Weiqin L, Shaoqiu T, Zhihui T, et al. Restricted peri-operative fluid administration adjusted by serum lactate level improved outcome after major elective surgery for gastrointestinal malignancy. Surgery. 2010;147:542–52.
Zhang J, Qiao H, He Z, Wang Y, Che X, Liang W. Intraoperative fluid management in open gastrointestinal surgery: goal-directed versus restrictive. Clinics (Sao Paulo). 2012;67:1149–55.
Zheng H, Guo H, Ye JR, Chen L, Ma HP. Goal-directed fluid therapy in gastrointestinal surgery in older coronary heart disease patients: randomized trial. World J Surg. 2013;37:2820–9.
Zeng K, Li Y, Liang M, Gao Y, Cai H, Lin C. The influence of goal-directed fluid therapy on the prognosis of elderly patients with hypertension and gastric cancer surgery. Drug Des Devel Ther. 2014;8:2113–9.
Salzwedel C, Puig J, Carstens A, Bein B, Molnar Z, Kiss K, et al. Perioperative goal-directed hemodynamic therapy based on radial arterial pulse pressure variation and continuous cardiac index trending reduces postoperative complications after major abdominal surgery: a multi-center, prospective, randomized study. Crit Care. 2013;17:R191.
McKenny M, Conroy P, Wong A, Farren M, Gleeson N, Walsh C, et al. A randomised prospective trial of intra-operative oesophageal Doppler-guided fluid administration in major gynaecological surgery. Anaesthesia. 2013;68:1224–31.
Bundgaard-Nielsen M, Jans Ø, Müller RG, Korshin A, Ruhnau B, Bie P, et al. Does goal-directed fluid therapy affect postoperative orthostatic intolerance? A randomized trial. Anesthesiology. 2013;119:813–23.
Zakhaleva J, Tam J, Denoya PI, Bishawi M, Bergamaschi R. The impact of intravenous fluid administration on complication rates in bowel surgery within an enhanced recovery protocol: a randomized controlled trial. Colorectal Dis. 2013;15:892–9.
Scheeren TW, Wiesenack C, Gerlach H, Marx G. 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. 2013;27:225–33.
Davies SJ, Wilson RJ. Preoperative optimization of the high-risk surgical patient. Br J Anaesth. 2004;93:121–8.
Gustafsson UO, Scott MJ, Schwenk W, Demartines N, Roulin D, Francis N, et al. Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations. World J Surg. 2013;37:259–84.
Bangash MN, Patel NS, Benetti E, Collino M, Hinds CJ, Thiemermann C, et al. Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow. Crit Care. 2013;17:R57.
Rollins KE, Lobo DN. Intraoperative goal-directed fluid therapy in elective major abdominal surgery: a meta-analysis of randomized controlled trials. Ann Surg. 2016;263:465–76.
Abbas SM, Hill AG. Systematic review of the literature for the use of oesophageal Doppler monitor for fluid replacement in major abdominal surgery. Anaesthesia. 2008;63:44–51.
Deans KJ, Minneci PC, Suffredini AF, Danner RL, Hoffman WD, Ciu X, et al. Randomization in clinical trials of titrated therapies: unintended consequences of using fixed treatment protocols. Crit Care Med. 2007;35:1509–16.
Ioannidis JP, Trikalinos TA. The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. CMAJ. 2007;176:1091–6.
No funding was received for this study.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
YS designed and conceived of the study; participated in acquisition, analysis, and interpretation of data; and drafted the manuscript. FC participated in acquisition, analysis, and interpretation of data and drafted the manuscript. CP participated in acquisition, analysis, and interpretation of data and drafted the manuscript. JLR participated in the design of the study, performed the statistical analysis, and helped to revise the manuscript. TJG conceived of the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
MEDLINE search strategy
exp Fluid Therapy/
exp Body Fluids/
exp Echocardiography, Doppler/
exp Echocardiography, Transesophageal/
exp Ultrasonography, Doppler/
exp Cardiac Output/
exp Monitoring, Intraoperative/
exp Blood Flow Velocity/
exp Stroke Volume/
exp Blood Pressure/
exp Pulmonary Artery/
exp Catheterization, Swan-Ganz/
exp Monitoring, Physiologic/
exp Intraoperative Care/or exp Intraoperative Period/
Oxygen/or exp Oxygen Consumption/
exp Critical Care/
exp Biological Oxygen Demand Analysis/
exp Vascular Access Devices/
exp Arterial Pressure/
exp Central Venous Catheters/
exp Venous Pressure/
exp Models, Cardiovascular/
exp Cardiography, Impedance/
exp Cardiopulmonary Resuscitation/
exp Plethysmography, Impedance/or Plethysmography/
exp Heart Function Tests/
exp Indicator Dilution Techniques/
exp Radioisotope Dilution Technique/
exp Lithium Chloride/
exp Heart Rate/
exp Spectrum Analysis/
exp Spectroscopy, Near-Infrared/
exp Electric Impedance/
goal directed therapy.tw.
exp Carbon Dioxide/
exp Pulsatile Flow/
exp Cardiac Volume/
exp Cardiac Output, Low/
exp Cardiac Output, High/
exp Diagnostic Techniques, Cardiovascular/
exp Plasma Substitutes/
1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50
exp Intestinal Mucosa/
exp Gastric Mucosa/
exp Splanchnic Circulation/
exp abdominal aortic surgery/or exp anastomosis, roux-en-y/or exp appendectomy/or exp biliary tract surgical procedures/or exp biliopancreatic diversion/or exp colectomy/or exp cystectomy/or exp endoscopy, digestive system/or exp enterostomy/or exp fundoplication/or exp gastrectomy/or exp gastroenterostomy/or exp gastropexy/or exp gastroplasty/or exp gastrostomy/or exp hemorrhoidectomy/or exp hepatectomy/or exp jejunoileal bypass/or exp liver transplantation/or exp pancreas transplantation/or exp pancreatectomy/or exp pancreaticoduodenectomy/or exp pancreaticojejunostomy/or exp peritoneovenous shunt/
exp Laparoscopy/or exp Hand-Assisted Laparoscopy/
exp Colonic Pouches/
exp Proctocolectomy, Restorative/
intermediate risk patients.mp.
high risk patients.mp.
52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65
51 and 66
exp Randomized Controlled Trial/
67 and 68
exp = explod
Risk of bias summary: review authors’ judgments about each risk-of-bias item for each included study. (PDF 341 kb)
Weighted kappa measurements to assess agreement between reviewers in rating quality of methodology of included trials. (PDF 48 kb)
Results of subgroup analysis and sensitivity analyses for mortality and overall complication rates. RR Risk ratio, CI 95% Confidence interval, ERP Enhanced recovery protocol, N Number of studies, n Number of participants, PAC Pulmonary arterial catheter, OEDM Esophageal Doppler monitor, CI# Cardiac index, DO 2 I Oxygen delivery index, SV Stroke volume, SVV Stroke volume variation. (1) Self-calibrating/calibrated pulse contour analysis monitor for example, Vigileo/Flotrac, LiDCO, PiCCO. (2) Arterial line monitoring equipment, central line and arterial line sampling, pulse oximeter, and other noninvasive monitors. (3) Pulse pressure variation (PPV), variation in arterial pulse pressure, and pleth variability index (PVI). (4) Mixed venous oxygen saturation, oxygen extraction ratio, or lactate. * Statistically significant. (DOCX 20 kb)
Meta-regression analysis for long-term mortality based on type of patients (high-risk versus non-high-risk), type of monitoring used, type of interventions (fluids versus fluids and inotropes), therapeutic goals, and whether in context with enhanced recovery programs (ERPs). RR Risk ratio. (PDF 100 kb)
Begg’s publication funnel plots on long-term mortality. RR Risk ratio. (PDF 127 kb)
Meta-regression analysis for short-term mortality. ERP Enhanced recovery program. (PDF 99 kb)
Publication funnel plots for short-term mortality. RR Risk ratio. (PDF 82 kb)
Meta-regression analysis for overall complication rates. RR Risk ratio, ERP Enhanced recovery program. (PDF 18 kb)
Begg’s publication funnel plots on overall complication rates. RR Risk ratio. (PDF 128 kb)
Begg’s publication funnel plots on time to first flatus pass (a), time to bowel movement (b), and time to tolerate oral diet (c). WMD Weighted mean difference. (PDF 54 kb)
About this article
Cite this article
Sun, Y., Chai, F., Pan, C. et al. Effect of perioperative goal-directed hemodynamic therapy on postoperative recovery following major abdominal surgery—a systematic review and meta-analysis of randomized controlled trials. Crit Care 21, 141 (2017). https://doi.org/10.1186/s13054-017-1728-8
- Goal-directed hemodynamic therapy
- Gastrointestinal function
- Abdominal surgery