After major surgery there is a significant risk of major complications and even death, particularly in the elderly and patients with significant cardiorespiratory disease. Major body cavity surgery causes a strong inflammatory response, which in turn causes a marked increase in oxygen requirements. To match the demand, patients will have to be able to elevate their cardiac output accordingly. The high-risk patient is one who can’t spontaneously elevate their cardiac output to the required level, and suffers an oxygen debt. The presence of an oxygen debt can be demonstrated despite normal haemodynamic and oxygen transport variables in both postoperative and critically ill patients; hence such patients may need therapy titrated to supranormal hemodynamic and oxygen transport goals. This may be achieved by the use of fluids and catecholamines to achieve ‘supra-normal’ oxygen delivery, an approach variously termed ‘goal directed therapy’, ‘preoptimization’, and ‘haemodynamic optimization’. All these strategies require monitoring of cardiac output, either by pulmonary artery catheterization or by other less invasive techniques.

The results of several studies and two meta-analyses support the use of perioperative optimization in high-risk patients undergoing major surgery. Goal Directed Therapy has been shown to improve outcome when commenced before surgery, but one recent study suggests that post-operative Goal Directed Therapy is also effective, and this does not require pre-operative ICU admission.

ABSTRACTS

1. Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445]. Pearse R, Dawson D, Fawcett J, et al. Crit Care. 2005;9(6):R687-93.

Introduction : Goal-directed therapy (GDT) has been shown to improve outcome when commenced before surgery. This requires pre-operative admission to the intensive care unit (ICU). In cardiac surgery, GDT has proved effective when commenced after surgery. The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery. Methods : This was a randomised controlled trial with concealed allocation. High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min-1 m-2 or to conventional management. Cardiac output was measured by lithium indicator dilution and pulse power analysis. Patients were followed up for 60 days. Results : Sixty-two patients were randomised to GDT and 60 patients to control treatment. The GDT group received more intravenous colloid (1,907 SD ± 878 ml versus 1,204 SD ± 898 ml; p < 0.0001) and dopexamine (55 patients (89%) versus 1 patient (2%); p < 0.0001). Fewer GDT patients developed complications (27 patients (44%) versus 41 patients (68%); p = 0.003, relative risk 0.63; 95% confidence intervals 0.46 to 0.87). The number of complications per patient was also reduced (0.7 SD ± 0.9 per patient versus 1.5 SD ± 1.5 per patient; p = 0.002). The median duration of hospital stay in the GDT group was significantly reduced (11 days (IQR 7 to 15) versus 14 days (IQR 11 to 27); p = 0.001). There was no significant difference in mortality (seven patients (11.3%) versus nine patients (15%); p = 0.59). Conclusion : Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay. The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission.

2. Meta-analysis of hemodynamic optimization: relationship to methodological quality. Poeze M, Greve JWM, Ramsay G. Critical Care 2005, 9:R771-R779 (DOI 10.1186/cc3902)

Introduction : To review systematically the effect of interventions aimed at hemodynamic optimization and to relate this to the quality of individual published trials. Methods : A systematic, computerized bibliographic search of published studies and citation reviews of relevant studies was performed. All randomized clinical trials in which adult patients were included in a trial deliberately aiming at an optimized or maximized hemodynamic condition of the patients (with oxygen delivery, cardiac index, oxygen consumption, mixed venous oxygen saturation and/or stroke volume as end-points) were selected. A total of 30 studies were selected for independent review. Two reviewers extracted data on population, intervention, outcome and methodological quality. Agreement between reviewers was high: differences were eventually resolved by third-party decision. The methodological quality of the studies was moderate (mean 9.0, SD 1.7), and the outcomes of the randomized clinical trials were not related to their quality. Results : Efforts to achieve an optimized hemodynamic condition resulted in a decreased mortality rate (relative risk ratio (RR) 0.75 (95% confidence interval (CI) 0.62 to 0.90) in all studies combined. This was due to a significantly decreased mortality in peri-operative intervention studies (RR 0.66 (95% CI 0.54 to 0.81). Overall, patients with sepsis and overt organ failure do not benefit from this method (RR 0.92 (95% CI 0.75 to 1.11).

Conclusion : This systematic review showed that interventions aimed at hemodynamic optimization reduced mortality. In particular, trials including peri-operative interventions aimed at the hemodynamic optimization of high-risk surgical patients reduce mortality. Overall, this effect was not related to the trial quality.

3. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. Sandham JD, Hull RD, Brant RF, et al. N Engl J Med 2003; 348: 5-14

Background : Some observational studies suggest that the use of pulmonary-artery catheters to guide therapy is associated with increased mortality. Methods : We performed a randomized trial comparing goal-directed therapy guided by a pulmonary- artery catheter with standard care without the use of a pulmonary-artery catheter. The subjects were high-risk patients 60 years of age or older, with American Society of Anesthesiologists (ASA) class III or IV risk, who were scheduled for urgent or elective major surgery, followed by a stay in an intensive care unit. Outcomes were adjudicated by observers who were unaware of the treatment-group assignments. The primary outcome was in-hospital mortality from any cause. Results : Of 3803 eligible patients, 1994 (52.4 percent) underwent randomization. The baseline characteristics of the two treatment groups were similar. A total of 77 of 997 patients who underwent surgery without the use of a pulmonary-artery catheter (7.7 percent) died in the hospital, as compared with 78 of 997 patients in whom a pulmonary-artery catheter was used (7.8 percent) - a difference of 0.1 percentage point (95 percent confidence interval, (2.3 to 2.5). There was a higher rate of pulmonary embolism in the catheter group than in the standard-care group (8 events vs. 0 events, P=0.004). The survival rates at 6 months among patients in the standard-care and catheter groups were 88.1 and 87.4 percent, respectively (difference, ¡0.7 percentage point [95 percent confidence interval, ¡3.6 to 2.2]; negative survival differences favor standard care); at 12 months, the rates were 83.9 and 83.0 percent, respectively (difference, ¡0.9 percentage point [95 percent confidence interval, ¡4.3 to 2.4]). The median hospital stay was 10 days in each group. Conclusions: We found no benefit to therapy directed by pulmonary-artery catheter over standard care in elderly, high-risk surgical patients requiring intensive care.

4. Meta-analysis of hemodynamic optimization in high-risk patients. Kern JW, Shoemaker WC. Crit Care Med. 2002 Aug;30(8):1686-92

Objective : The aim of this evidence-based report was to review pertinent randomized controlled studies that describe hemodynamic goals in acute, critically ill patients and to evaluate outcome of resuscitation therapy in association with physiologic, clinical, and therapeutic influences. Methods : MEDLINE was the source of randomized controlled studies written in English. The inclusion criteria were acutely ill, high-risk elective surgery, trauma, and septic patients. The goals of therapy were to resuscitate to either normal or supranormal values; the latter were described as a cardiac index of >4.5 L/min x m2, pulmonary artery occlusion pressure of <18 mm Hg, oxygen delivery of >600 ml/min x m2, and oxygen consumption of >170 ml/min x m2. The outcome criterion was survival or death. We found 21 randomized clinical trials described in 20 articles. The studies were divided into groups based on the time that goals were implemented (i.e., “early,” 8 to 12 hrs postoperatively or before organ failure, vs. “late,” or after onset of organ failure) and the severity of illness, determined by the control group mortality as >20% (12 studies) or <15% (nine studies). Results : In severely ill patients (control mortalities group >20%), six studies had a 23% mortality difference (p <.05) between the control and protocol groups with early optimization, but seven studies optimized after the development of organ failure did not have significantly improved mortality. Moreover, outcome was not significantly improved in less severely ill patients (control mortalities group <15%) and normal values as goals or when therapy did not improve oxygen delivery.

Conclusion: Review of 21 randomized controlled trials with various approaches to treatment revealed statistically significant mortality reductions, with hemodynamic optimization, when patients with acute critical illness were treated early to achieve optimal goals before the development of organ failure, when there were control group mortalities of >20% and when therapy produced differences in oxygen delivery between the control and protocol groups.

5. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. Wilson J, Woods I, Fawcett J, et al. BMJ 1999; 318: 1099-103

Objectives : To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome. Design : Randomised controlled trial with double blinding between inotrope groups. Setting York District Hospital, England. Subjects : 138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. Interventions : Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care. Main outcome measures : Hospital mortality and morbidity. Results : Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P = 0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital.

Conclusion : Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.

6. A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients. Boyd O, Grounds RM, Bennett ED. JAMA 1993; 270: 2699-707

Objective : To assess the effect of deliberate perioperative increase in oxygen delivery on mortality and morbidity in patients who are at high risk of both following surgery. Design : Prospective, randomized clinical trial. Setting : A teaching hospital general intensive care unit, London, England. Patients : A total of 107 surgical patients, who were assessed as high risk from previously identified criteria, were studied during an 18-month period. Interventions : Patients were randomly assigned to a control group (n = 54) that received best standard perioperative care, or to a protocol group (n = 53) that, in addition, had deliberate increase of oxygen delivery index to greater than 600 ml/min per square meter by use of dopexamine hydrochloride infusion. Outcome measures : Mortality and complications were assessed to 28 days postoperatively. Results : Groups were similar with respect to demographics, admission criteria, operation type, and admission hemodynamic variables. Groups were treated similarly to maintain blood pressure, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure; however, once additional treatment with dopexamine hydrochloride had been given, the protocol group had significantly higher oxygen delivery preoperatively (median, 597 vs 399 ml/min per square meter; P < .001) and postoperatively (P < .001). Results indicate a 75% reduction in mortality (5.7% vs 22.2%; P = .015) and a halving of the mean (+/- SEM) number of complications per patient (0.68 [+/- 0.16] vs 1.35 [+/- 0.20]; P = .008) in patients randomized to the protocol group. Conclusion : Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients.

7. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Shoemaker WC, Appel PL, Kram HB, et al. Chest 1988; 94: 1176-1186

Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI, DO2, and VO2 than nonsurvivors. The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism. We tested this hypothesis in two series. In series 1, prospectively allocated by services, mortality and morbidity of the control group were significantly greater than those of the protocol group. In series 2, patients who fulfilled previously defined high-risk criteria were preoperatively randomized to one of three monitoring/treatment groups: CVP-control group, PA-control group and PA-protocol group. Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different, but PA-protocol group mortality was significantly reduced compared with its control group. The PA-protocol group had reduced complications, duration of hospitalization, duration in ICU, and mechanical ventilation, and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses.

Peri-operative interventions aimed at the hemodynamic optimization of high-risk surgical patients reduce mortality. However the use of hemodynamic optimization as a therapy to improve outcome during sepsis with established organ failure does not reduce mortality.