The quality of the individual studies as assessed by the Jadad score is presented in Table 4. It is apparent that very few of the studies were performed in a double-blind manner and nearly all were done in a single center. Figure 4 shows an OR plot of mortality split by quality. The higher quality studies (with a Jadad score ≥3) fail to show a significant reduction in mortality, as opposed to lower quality studies that do. The effect of quality on morbidity is shown in Figure 5. In contrast to mortality, there is a significant reduction in morbidity irrespective of trial quality. The point estimate of effect is similar for the 2 groups but the CI for the lower quality studies is wider.
This systematic review and meta-analysis has demonstrated that preemptive hemodynamically targeted therapy in the perioperative period can reduce both morbidity and mortality after surgery. Although over time the control-group mortality decreased, suggesting a lowering of the threshold for the performance of these techniques, the impact of this therapy remains even for the lower risk categories of patients. Although mortality was not proven to be reduced in the lower risk group, the effects on reducing morbidity were still valid, confirming the assumption that the technique of targeted hemodynamic intervention is beneficial across risk profile groups and across monitoring technologies.
There are a number of reasons why the control mortality may have decreased over time. These include the possibilities of better overall care thus decreasing mortality for similar patients, clinicians learning from previous early published studies and therefore drifting their practice toward lower risk groups, and also the likelihood that as technology has improved and become less invasive, the technique has gained more credibility. This can be seen especially in the way the pulmonary artery catheter, with all of its incumbent controversies,41,42 has now been largely superseded by less-invasive hemodynamic monitoring techniques such as esophageal Doppler-based systems and arterial pressure analysis.43 It is of note that, although the debate surrounding the pulmonary artery catheter focused on an inability to prove a significant beneficial effect to patients,44–46 this study has demonstrated a highly significant reduction in both morbidity and mortality with the use of this technique for these patients. The same is also true for the newer generation of monitoring modalities.
The burden of complications and mortality for surgical patients is becoming increasingly understood.1,3 Many authors have now demonstrated that the rate of complications is related to a number of factors that include the type of surgery performed, the skill of the operating team, the overall “fitness” of the patient, and also the provision of a number of techniques that have shown to reduce the risk.47–50
This study confirms that hemodynamic targeted therapy can reduce this risk. Khuri et al.1 demonstrated that this reduction in postoperative complications can have long-lasting effects on the survival of these patients, outside of the remit of a short-term follow-up period in these studies. If this hypothesis is correct, then the upfront costs of this relatively inexpensive technique are easily outweighed by the longer-term benefits. Irrespective of this, the prevention of complications is in itself a mechanism for saving significant amounts of health care resources, because it is often these complications that prolong hospital length of stay and result in multiple costly interventions. Recent work published in the New England Journal of Medicine has also raised the possibility that survival is related to the identification and then immediate and appropriate management of these complications.3 It remains a possibility that patients being studied in trials such as ours have a lower than normal complication and mortality rate for this very reason. By participating in a study, they are frequently assessed and probably offered a quality of care that is above the standard approach.
This study has a number of limitations. We made no attempt to correct for the type or quantity of fluids or inotropes given, because they are inconsistently reported in the literature and have a demonstrable wide variability in their dosing across studies. Also, a number of grouped studies rather than individual patient data were meta-analyzed. Some authors would suggest that this would be a more robust methodology, although obtaining the original data is often not possible, especially over such a long period such as this. It also has to be recognized that very few of the studies that we identified were performed in a high-quality design. It is almost impossible to have a properly double-blind study when the 2 groups need to have therapy targeted to different protocols. It is also of note that the majority of the trials were single-centered and performed on a limited sample size. The heterogeneity of this analysis is therefore relatively high, although the results remain consistent across a number of subgroups and sensitivity analyses, thereby helping to affirm our assumptions. We have also reported on studies that describe the incidence of postoperative complications. It has to be recognized that the reporting of complications is not consistent and that the definitions used can differ, limiting the applicability of some of our findings.
This meta-analysis suggests that a preemptive targeted approach to the management of hemodynamics in the perioperative period may reduce morbidity and mortality for high-risk surgical patients.
All authors were involved and helped in the design, execution, analysis, and writing of the manuscript.
Andrew Rhodes, LiDCO (lecturing fees and grant), Edwards Lifesciences (lecturing fees), Hutchinson Medical (research support), PulseCor (research support), Cheetah (research support), and Abbott (consulting fees); Mark A. Hamilton, Deltex Medical (lecturing fees), Edwards Lifesciences (lecturing fees), and Hutchinson Medical (research support); and Maurizio Cecconi, LiDCO (lecturing fees and grant), Edwards Lifesciences (lecturing fees), Hutchinson Medical (research support), PulseCor (research support), and Chhetah (research support).
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