Clinical review: Goal-directed therapy-what is the evidence in surgical patients? The effect on different risk groups

Abstract

Patients with limited cardiac reserve are less likely to survive and develop more complications following major surgery. By augmenting oxygen delivery index (DO2I) with a combination of intravenous fluids and inotropes (goal directed therapy (GDT)), postoperative mortality and morbidity of high-risk patients may be reduced. However, although most studies suggest that GDT may improve outcome in high-risk surgical patients, it is still not widely practiced. We set out to test the hypothesis that GDT results in greatest benefit in terms of mortality and morbidity in patients with the highest risk of mortality and have undertaken a systematic review of the current literature to see if this is correct. We performed a systematic search of Medline, Embase and CENTRAL databases for randomized controlled trials (RCTs) and reviews of GDT in surgical patients. To minimize heterogeneity we excluded studies involving cardiac, trauma, and paediatric surgery. Extremely high risk, high risk and intermediate risks of mortality were defined as >20%, 5 to 20% and <5% mortality rates in the control arms of the trials, respectively. Meta analyses were performed and Forest plots drawn using RevMan software. Data are presented as odd ratios (OR; 95% confidence intervals (CI), and P-values). A total of 32 RCTs including 2,808 patients were reviewed. All studies reported mortality. Five studies (including 300 patients) were excluded from assessment of complication rates as the number of patients with complications was not reported. The mortality benefit of GDT was confined to the extremely high-risk group (OR = 0.20, 95% CI 0.09 to 0.41; P < 0.0001). Complication rates were reduced in all subgroups (OR = 0.45, 95% CI 0.34 to 0.60; P < 0.00001). The morbidity benefit was greatest amongst patients in the extremely high-risk subgroup (OR = 0.27, 95% CI 0.15 to 0.51; P < 0.0001), followed by the intermediate risk subgroup (OR = 0.43, 95% CI 0.27 to 0.67; P = 0.0002), and the high-risk subgroup (OR 0.56, 95% CI 0.36 to 0.89; P = 0.01). Despite heterogeneity in trial quality and design, we found GDT to be beneficial in all high-risk patients undergoing major surgery. The mortality benefit of GDT was confined to the subgroup of patients at extremely high risk of death. The reduction of complication rates was seen across all subgroups of GDT patients.

Current concepts in fluid therapy and non-invasive haemodynamic monitoring

“…Despite producing proof of ongoing usefulness of GDT strategies in the light of protocolised patient care is becoming challenging, they undoubtedly have their place in optimising individual's haemodynamics, tissue perfusion and, in turn, reducing morbidity and perhaps, mortality (9,(16)(17)(18). As recently suggested in a consensus, the ideal haemodynamic monitor should provide accurate and reproducible measurements of relevant variables that can be interpreted, should be readily available and easy to use, operator-independent, have a rapid response time, be harmless, cost-effective and should help guide therapy (29).…”

“…It is possible that treatment of septic patients, especially with wide adoption of the Surviving Sepsis Campaign guidelines (15) has improved enough for benefits of GDT to be more difficult to prove in trials. In surgical patients, it seems that GDT is beneficial throughout the population, but those at higher risk for complications benefit more (16)(17)(18)(19). GDT has also been established as an important part of intensive care therapy (20).…”

Multimodal individualized concept of hemodynamic monitoring

“…Their data also suggested that dobutamine use resulted in the development of parasympathetic autonomic dysfunction, which can potentially be harmful. However, in two recent meta-analyses, it was found that patients in the treatment groups received significantly more dobutamine, but morbidity and mortality in general, and also postoperative cardiac complications were significantly reduced when advanced hemodynamic monitoring-based intraoperative management is applied [25,26].…”

Perioperative Goal-Directed Therapy

“…Recent meta-analysis found that the reduction in mortality with perioperative GDT was significant only in patients with an extremely high (420%) mortality rate, and that mortality rate has declined significantly over time. 24,70 It is likely that patients with the highest risk of mortality benefit most from aggressive GDT (ie, PAC placement, use of vasoactive substances to target supranormal hemodynamic parameters), whereas most patients derive a morbidity benefit from perioperative GDT. Unfortunately, survey data show that there is still an underutilization of perioperative GDT, partially owing to a perceived lack of benefit as well as inadequate availability of or training with various monitors.…”