The observation that patients who survive major surgery have elevated cardiac output and oxygen delivery values led to the development of goal-directed therapy, otherwise known as haemodynamic optimisation. Cardiac output and oxygen delivery are augmented by the administration of intravenous fluids, with or without the addition of inotropic agents such as dobutamine or dopexamine. A treatment algorithm guided by haemodynamic monitoring drives therapy. Treatment goals are often supranormal values of blood-flow-related variables (e.g. cardiac index, oxygen delivery, stroke volume).

Two systematic reviews with meta-analyses studying this strategy in the perioperative setting have concluded that mortality is reduced using this approach 1112. The first review showed a significant reduction in mortality if therapy was initiated preoperatively (two trials, 195 patients). The second review of 21 trials (13 perioperative trials, > 1008 patients) revealed significant mortality reduction when patients were treated before the development of organ failure, when there were control group mortalities > 20% and when therapy produced differences in oxygen delivery between the control and protocol groups 12. An additional systematic review of perioperative fluid volume optimisation following proximal femoral fracture (two studies, 130 patients) showed a reduction in the hospital length of stay in the intervention group 13. However, a recent large perioperative RCT failed to show any benefit 14. The large RCT has been criticised on a number of design and conduct issues, and the systematic reviews exhibit significant heterogeneity. This is a good example of a large RCT producing a different result from previous systematic reviews.

Cardiovascular disease is an important cause of perioperative morbidity and mortality. This is thought to be due to sympathetic over-activity increasing heart rate, myocardial workload and the incidence of arrhythmias. Perioperative blockade of beta-adrenergic receptors may be protective against cardiovascular complications such as myocardial infarction and arrhythmias, and therefore may reduce mortality.

Three (small) randomised trials examined the use of beta-blockers in surgical patients with known or suspected coronary disease 151617. Two of these trials demonstrated a significant reduction in mortality in the intervention group. However, one study (200 patients undergoing elective major noncardiac surgery) stopped beta-blockers prior to surgery in patients in the control group who were already taking them, and this is inconsistent with current guidelines 15. In the other study (112 patients presenting for elective major vascular surgery), patients were preselected on the basis of positive dobutamine stress echocardiograms from an initial cohort of 1351 patients, which makes it difficult to generalise these data to a population not selected in this manner 16. In the third study (107 patients undergoing elective knee arthroplasty), a reduced prevalence and duration of postoperative myocardial ischaemia detected with Holter monitoring was demonstrated 17.

There are no large RCTs (> 1000 patients) or systematic reviews that demonstrate the effect of this intervention on mortality. Nonetheless, the results of these small studies suggest that perioperative beta-blockade improves outcome in patients with known or suspected heart disease. The American College of Cardiology and American Heart Association guidelines now recommend this strategy 18. A large international RCT is currently being conducted to test the hypothesis that perioperative administration of beta-adrenergic blockers in patients with risk factors for ischaemic heart disease reduces mortality (the 'POISE' study).

Improved postoperative pain relief is important for patient comfort and may decrease the hospital stay and lead to reductions in morbidity. Improved blood flow consequent on sympatholysis has additional potential benefits, including a reduction in thromboembolic complications and improved gastrointestinal function.

A large number of RCTs in this area have been summarised in several systematic reviews with meta-analysis. Pooled analysis of 141 randomised trials involving a total of 9559 patients revealed a 30% reduction in mortality associated with neuraxial blockade and significant reductions in thromboembolic and respiratory complications 19. Pain relief with epidural analgesia with local anaesthetic agents has been demonstrated to be superior to parenteral opioids alone in a meta-analysis of 100 studies 20. Regional anaesthesia for hip fracture surgery when compared with general anaesthesia produced comparable results for most of the outcomes studied (16 trials, 2191 patients). Regional anaesthesia may have reduced short-term mortality, but no conclusions could be drawn for longer-term mortality 21. For hip and knee replacement surgery short-term postoperative pain relief was improved with regional anaesthesia but minor complications were more frequent, and there were insufficient data to draw conclusions on the frequency of rare complications from epidural analgesia, postoperative morbidity or mortality, functional outcomes, or length of hospital stay 22. Following abdominal surgery, the time to return of gastrointestinal function was reduced with epidural anaesthesia but there were insufficient data to comment on mortality 23.

The concept that improving nutritional status and minimising catabolism will improve perioperative outcome has been tested in a large number of RCTs, and two systematic reviews have addressed questions in this area. A systematic review of 11 studies with 837 patients demonstrated that early enteral feeding postoperatively after gastrointestinal surgery reduced infection rates and the length of stay but did not significantly reduce mortality 24. When compared with enteral nutrition, total parenteral nutrition does not influence the death rate of surgical patients, but may reduce the complication rate, especially in malnourished patients 25.

The bactericidal activity of neutrophils is mediated by oxidative killing by the production of superoxide radicals, the rate of generation of which is proportional to the partial pressure of oxygen. At surgical wound sites this is likely to be low due to disrupted vascular supply and decreased blood flow perioperatively. Resistance to infection may be enhanced by the administration of supplemental oxygen to increase tissue oxygenation and augment neutrophil function. A moderate-sized randomised trial (500 patients undergoing elective general surgery) in which 30% or 80% oxygen was administered perioperatively demonstrated a reduction in wound infection in the higher FiO₂ group 26. However, a more recent small study of similar design found an increase in infection in those administered the higher FiO₂ 27. There are no RCTs or systematic reviews that demonstrate a beneficial effect of this intervention on mortality.

Inhibition of physiological temperature control mechanisms, peripheral redistribution of body heat during general anaesthesia and the cool operating room environment contribute to perioperative hypothermia. Immune cell function becomes impaired as a consequence of low tissue oxygenation and hypothermia. Temperature reduction also has an adverse effect on collagen deposition. These factors have an unfavourable effect on surgical wound healing.

Four small to moderate-sized clinical studies (60–300 patients) have compared active warming (normothermia) with the standard of care (resulting in mild hypothermia) 28293031. In 200 patients undergoing elective colorectal surgery, those randomised to receive active warming had a reduced incidence of wound infection 29. In 60 patients undergoing primary hip arthroplasties, the postoperative blood loss and transfusion requirements were significantly greater in the hypothermic patients 31. In 300 patients undergoing abdominal, thoracic or vascular surgical procedures with documented coronary artery disease, or risk factors for coronary disease, perioperative cardiac events and ventricular tachycardia occurred less frequently in the normothermic group 28. In 150 patients undergoing elective major abdominal surgery, a decreased duration of postanaesthetic recovery was observed in the normothermic group 30. There are no RCTs or systematic reviews that demonstrate a beneficial effect of this intervention on mortality.

Differences in case-mix-adjusted mortality have been noted between countries where levels of critical care provision differ 32.

In a systematic review of 27 studies, high-intensity ICU physician staffing versus low-intensity ICU physician staffing was associated with reduced hospital and ICU mortality and with reduced hospital and ICU length of stay 33. No RCTs (large or small) or systematic reviews exist to test the hypothesis that critical provision postoperatively reduces mortality.