There is a subgroup of patients during some surgical procedures that have a high potential for complications during the perioperative period. To explore the possible interventions that might reduce the incidence of complications in these patients, a substantial number of randomized controlled clinical trials on perioperative hemodynamic stabilization are necessary. A systematic review of these clinical trials would be considered the highest level of evidence and guide for interventions that improve outcome.8 There is still a need to explore perioperative hemodynamic control in high-risk surgical patients, considering not only the diverse markers of tissue perfusion, but also the targets for treatment. We focused on those trials comprising high-risk surgical patients with no evident organ dysfunction before surgery and submitted to an early protocol of hemodynamic treatment, trying to prevent occult tissue hypoperfusion.
There are several previous systematic reviews on high-risk surgical patients studied using a hemodynamic protocol to maintain adequate tissue perfusion during the perioperative period.
Three recent reviews involving a few series of randomized controlled studies explored different aspects of hemodynamic stabilization. Bundgaard-Nielsen et al.12 identified 9 studies in which a goal-directed therapeutic strategy was used to maximize flow-related hemodynamic variables in surgical patients, intra- and postoperatively. They verified that the treatment strategy reduced gastrointestinal complications and hospital length of stay. Abbas and Hill13 analyzed the use of esophageal Doppler on hemodynamic control with fluids in major abdominal surgery, selecting 5 studies comprising 420 patients, and demonstrated that there was a reduction in hospital stay in the intervention group. Giglio et al.14 selected 16 studies involving perioperative monitoring and manipulation of hemodynamic variables to reach normal or supranormal values and also concluded that goal-directed hemodynamic therapy reduces gastrointestinal complications after major surgery, as tissue perfusion is maintained.
This review differs from previously published reviews on hemodynamic monitoring and control because it focuses on surgical patients with no organ failure before surgery, with a high risk of complications and death, and submitted to a specific protocol to maintain tissue perfusion involving cardiac output, oxygen delivery/consumption, and its derived variables, such as S|v[Combining Macron]O2. With these filters, 32 randomized clinical trials were recovered with >5000 patients, the largest number of individuals in a review on this topic.
In the present review, we found that in high-risk surgical patients with no evident organ dysfunction before surgery, the use of a protocol to maintain adequate hemodynamic status and tissue perfusion reduced the mortality rate and the possibility of organ failure in the postoperative period (Table 5). Therefore, strategies to ensure adequate perioperative tissue perfusion should be adopted. It is surprising that in a recent publication, Pearse et al.15 showed a different outcome in the United Kingdom, where the high-risk surgical population accounted for 12.5% of surgical procedures but for >80% of deaths. Despite the high mortality rates, fewer than 15% of these patients were admitted to intensive care. It could be that the care providers did not focus on tissue perfusion management for many of those patients.
When analyzing the methodological quality of the trials, we found that a significant percentage of the randomized controlled clinical studies involving therapeutic interventions that aimed at hemodynamic control had some methodological deficiency. Our results showed that, independent of the methodological quality score, perioperative hemodynamic control significantly reduced the incidence of organ failure. However, the methodological score influenced mortality in overall effect. Studies classified as 10 to 16 according to Chalmers score7 did not result in a significant reduction in mortality, even though there was a tendency toward a reduction (OR: 0.79; 95% CI: 0.64–0.99; moderate heterogeneity; P > 0.05) (Table 5). Additional well-designed randomized controlled studies are necessary to clarify this discrepancy and ultimately to determine whether mortality can be reduced through the maintenance of perioperative tissue perfusion in high-risk surgical patients.
The analysis of the subgroup whose control group had a higher mortality rate (>20%) showed that perioperative hemodynamic control significantly reduced mortality (Table 5). From this finding, we understand that the higher the risk involved, the more benefit patients have with a protocol to maintain tissue perfusion. In this highest-risk subgroup, there were probably more patients submitted to more complex operations, more elderly patients, and probably more patients with some limitation in physiological reserves. In the other 2 subgroups whose control groups had mortality rates of <20%, specific hemodynamic control protocols did not significantly reduce mortality. A lower mortality rate in the control group probably indicates selection of individuals with better clinical conditions having less-complex elective operations. The probability of a state of tissue hypoperfusion in these patients then seems to be greatly reduced. However, maintaining tissue perfusion perioperatively significantly reduced the incidence of organ dysfunction in all groups of patients (Table 5).
A well-defined protocol with explicit goals is important for the results, which tend to be better than in studies comparing the use of a pulmonary artery catheter with standard care (Sandham et al.16). For example, Lobo et al.17 randomized high-risk surgical patients, and with a defined goal (DO2I >600 mL · min−1 · m−2) and a specific algorithm for treatment (fluids, drugs) were capable of considerably and significantly reducing the mortality rate (OR: 0.19; 95% CI: 0.04–0.88), as compared with Sandham et al. (OR: 1.01; 95% CI: 0.73–1.41).
In addition, we found that the use of a pulmonary artery catheter as a guide for hemodynamic treatment in the high-risk surgical patient significantly reduced the mortality rate (Table 5), contradicting those who found an increase in mortality rate with its use.18 High-risk surgical patients with no evident signs of preoperative tissue hypoperfusion and those without any kind of organ failure may benefit from pulmonary artery catheterization and hemodynamic control, which differs from many critically ill patients, some with multiple organ failure, who have progressive and nonreversible tissue damage and will not benefit from any kind of monitoring and treatment.
Studies for analysis were selected in which perioperative hemodynamic control was guided by cardiac index, DO2I, and V[Combining Dot Above]O2I, where we found a significant reduction in the incidence of both mortality and organ failure (Table 5). The literature has shown the insensitivity of using clinical variables such as arterial blood pressure, heart rate, consciousness level, urinary volume, and perfusion of extremities to determine the presence of tissue hypoperfusion in both clinical and stable surgical patients.19 We recommend use of tools that clearly help to recognize and maintain tissue perfusion and can significantly contribute to the final result: reduction in mortality rate and organ failure incidence. In the present review, 18 of the 31 selected studies had hemodynamic control guided by cardiac index, DO2I, and V[Combining Dot Above]O2I and a significantly reduced incidence of postoperative complications.
In this meta-analysis, we found just one study in which lactate was used as a specific marker for perioperative hemodynamic control. There was no significant reduction in mortality, but organ dysfunction was significantly reduced. Similar to Sv[Combining Macron]O2 and ScvO2, in high-risk surgical patients, additional studies will be necessary to better understand the role of lactate as a guide for perioperative hemodynamic management.
In summary, the present meta-analysis suggests that, in high-risk surgical patients with no evident organ dysfunction before surgery, maintaining tissue perfusion perioperatively according to a specific protocol reduces postoperative mortality and morbidity. Furthermore, the higher the risk, the more benefit there is from hemodynamic control. The use of the pulmonary artery catheter, and cardiac index, DO2I, and V[Combining Dot Above]O2I as targets for hemodynamic control reduces postoperative mortality and organ dysfunction in this group of patients. Additional studies with Sv[Combining Macron]O2, ScvO2, and lactate as markers of tissue perfusion in the high-risk surgical patient should be performed to clarify their potential as goals for perioperative hemodynamic control and reduction of postoperative complications and mortality. Finally, methodological trial quality seems to influence mortality analysis in perioperative patients more than in other subsets of patients, such as those with sepsis and organ failure.
1. Boyd O. Optimisation of oxygenation and tissue perfusion in surgical patients. Intensive Crit Care Nurs 2003;19:171–81
2. Shoemaker WC, Appel PL, Kram HB. Measurement of tissue perfusion by oxygen transport patterns in experimental shock and in high-risk surgical patients. Intensive Care Med 1990;16:S135–44
3. Boyd O, Jackson N. How is risk defined in high-risk surgical patient management? Crit Care 2005;9:390–6
4. 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
5. Donati A, Loggi S, Preiser JC, Orsetti G, Munch C, Gabbanelli V, Pelaia P, Pietropaoli P. Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients. Chest 2007;132:1817–24
6. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240: 205–13
7. Chalmers TC, Smith H Jr, Blackburn B, Silverman B, Schroeder B, Reitman D, Ambroz A. A method for assessing the quality of a randomized control trial. Control Clin Trials 1981;2:31–49
8. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N, Mason J, Middleton P, Mrukowicz J, O'Connell D, Oxman AD, Phillips B, Schunemann HJ, Edejer TT, Varonen H, Vist GE, Williams JW Jr, Zaza S. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490
9. Heyland DK, Cook DJ, King D, Kernerman P, Brun-Buisson C. Maximizing oxygen delivery in critically ill patients: a methodologic appraisal of the evidence. Crit Care Med 1996;24:517–24
10. Kern JW, Shoemaker WC. Meta-analysis of hemodynamic optimization in high-risk patients. Crit Care Med 2002; 30:1686–92
11. Poeze M, Greve JW, Ramsay G. Meta-analysis of hemodynamic optimization: relationship to methodological quality. Crit Care 2005;9:R771–9
12. 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
13. 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
14. Giglio MT, Marucci M, Testini M, Brienza N. Goal-directed haemodynamic therapy and gastrointestinal complications in major surgery: a meta-analysis of randomized controlled trials. Br J Anaesth 2009;103:637–46
15. Pearse RM, Harrison DA, James P, Watson D, Hinds C, Rhodes A, Grounds RM, Bennett ED. Identification and characterisation of the high-risk surgical population in the United Kingdom. Crit Care 2006;10:R81
16. Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ, Laporta DP, Viner S, Passerini L, Devitt H, Kirby A, Jacka M. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med 2003;348:5–14
17. Lobo SM, Salgado PF, Castillo VG, Borim AA, Polachini CA, Palchetti JC, Brienzi SL, de Oliveira GG. Effects of maximizing oxygen delivery on morbidity and mortality in high-risk surgical patients. Crit Care Med 2000;28:3396–404
18. Connors AF Jr, Speroff T, Dawson NV, Thomas C, Harrell FE Jr, Wagner D, Desbiens N, Goldman L, Wu AW, Califf RM, Fulkerson WJ Jr, Vidaillet H, Broste S, Bellamy P, Lynn J, Knaus WA. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. JAMA 1996;276:889–97
19. Rady MY. Bench-to-bedside review: resuscitation in the emergency department. Crit Care 2005;9:170–6
20. Bloos F, Reinhart K. Venous oximetry. Intensive Care Med 2005;31:911–3
21. Springer RR, Stevens PM. The influence of PEEP on survival of patients in respiratory failure: a retrospective analysis. Am J Med 1979;66:196–200
22. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368–77
23. Polonen P, Ruokonen E, Hippelainen M, Poyhonen M, Takala J. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg 2000;90:1052–9
24. 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;226:229–36
25. Berlauk JF, Abrams JH, Gilmour IJ, O'Connor SR, Knighton DR, Cerra FB. Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery: a prospective, randomized clinical trial. Ann Surg 1991;214:289–97
26. Bishop MH, Shoemaker WC, Appel PL, Meade P, Ordog GJ, Wasserberger J, Wo CJ, Rimle DA, Kram HB, Umali R, Kennedy F, Shuleshko J, Stephen CM, Shori SK, Thadepalli HD. Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation endpoints in severe trauma. J Trauma 1995;38:780–7
27. Boldt J, Papsdorf M, Piper S, Padberg W, Hempelmann G. Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery. Acta Anaesthesiol Scand 1998;42:941–7
28. Bonazzi M, Gentile F, Biasi GM, Migliavacca S, Esposti D, Cipolla M, Marsicano M, Prampolini F, Ornaghi M, Sternjakob S, Tshomba Y. 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
29. 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
30. Chytra I, Pradl R, Bosman R, Pelnar P, Kasal E, Zidkova A. Esophageal Doppler-guided fluid management decreases blood lactate levels in multiple-trauma patients: a randomized controlled trial. Crit Care 2007;11:R24
31. 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
32. Fleming A, Bishop M, Shoemaker W, Appel P, Sufficool W, Kuvhenguwha A, Kennedy F, Wo CJ. Prospective trial of supranormal values as goals of resuscitation in severe trauma. Arch Surg 1992;127:1175–9
33. Gan TJ, Soppitt A, Maroof M, el-Moalem H, Robertson KM, Moretti E, Dwane P, Glass PS. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 2002;97:820–6
34. Kapoor PM, Kakani M, Chowdhury U, Choudhury M, Lakshmy R, Kiran U. Early goal-directed therapy in moderate to high-risk cardiac surgery patients. Ann Card Anaesth 2008;11:27–34
35. Lobo SM, Lobo FR, Polachini CA, Patini DS, Yamamoto AE, de Oliveira NE, Serrano P, Sanches HS, Spegiorin MA, Queiroz MM, Christiano AC Jr, Savieiro EF, Alvarez PA, Teixeira SP, Cunrath GS. Prospective, randomized trial comparing fluids and dobutamine optimization of oxygen delivery in high-risk surgical patients [ISRCTN42445141]. Crit Care 2006;10:R72
36. Lopes MR, Oliveira MA, Pereira VO, Lemos IP, Auler JO Jr, 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
37. Mythen MG, Webb AR. Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Arch Surg 1995;130:423–9
38. 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
39. 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
40. Schultz RJ, Whitfield GF, LaMura JJ, Raciti A, Krishnamurthy S. The role of physiologic monitoring in patients with fractures of the hip. J Trauma 1985;25:309–16
41. 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 1997;315:909–12
42. Stone MD, Wilson RJ, Cross J, Williams BT. Effect of adding dopexamine to intraoperative volume expansion in patients undergoing major elective abdominal surgery. Br J Anaesth 2003;91:619–24
43. Takala J, Meier-Hellmann A, Eddleston J, Hulstaert P, Sramek V. Effect of dopexamine on outcome after major abdominal surgery: a prospective, randomized, controlled multicenter study. European Multicenter Study Group on Dopexamine in Major Abdominal Surgery. Crit Care Med 2000;28:3417–23
44. Ueno S, Tanabe G, Yamada H, Kusano C, Yoshidome S, Nuruki K, Yamamoto S, Aikou T. 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
45. Valentine RJ, Duke ML, Inman MH, Grayburn PA, Hagino RT, Kakish HB, Clagett GP. Effectiveness of pulmonary artery catheters in aortic surgery: a randomized trial. J Vasc Surg 1998;27:203–11
46. Velmahos GC, Demetriades D, Shoemaker WC, Chan LS, Tatevossian R, Wo CC, Vassiliu P, Cornwell EE III, Murray JA, Roth B, Belzberg H, Asensio JA, Berne TV. Endpoints of resuscitation of critically injured patients: normal or supranormal? A prospective randomized trial. Ann Surg 2000;232: 409–18
47. Venn R, Steele A, Richardson P, Poloniecki J, Grounds M, Newman P. 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 2002;88:65–71
48. Wakeling HG, McFall MR, Jenkins CS, Woods WG, Miles WF, Barclay GR, Fleming SC. Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery. Br J Anaesth 2005;95:634–42
49. Wilson J, Woods I, Fawcett J, Whall R, Dibb W, Morris C, McManus E. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ 1999;318:1099–103
50. Ziegler DW, Wright JG, Choban PS, Flancbaum L. A prospective randomized trial of preoperative “optimization” of cardiac function in patients undergoing elective peripheral vascular surgery. Surgery 1997;122:584–92