Perioperative Optimisation

 SMJ 2003 49(1): 6-9

J Harten¹, J Kinsella²

Research Fellow¹, Senior Lecturer², University Department of Anaesthesia , University of Glasgow

Approximately 3.3 million non-day case operations, emergency and elective, are performed in the UK each year with an overall 30-day mortality of approximately 1%¹. In selected groups of patients mortality can be significantly higher with mortality rates up to 35 %². An audit in Scotland confirmed that elderly patient undergoing emergency abdominal surgery have an overall 30-day mortality of about 30% ³. Mortality is mostly delayed (>50% occurring after the 5^th postoperative day) and frequently occurs in the intensive care unit, commonly from multi-organ failure, following a protracted period of illness. Relevant predictors of risk include surgical factors such as body cavity, prolonged and emergency surgery and patient factors such as co-morbidity and extremes of age⁴.

Definition of perioperative optimisation

Perioperative optimisation is the preventive manipulations of physiological parameters during the perioperative period. This specific strategy aims, in addition to standard anaesthetic and surgical care, to decrease morbidity and mortality following surgery. The term optimisation is however misleading as many of the studies have only attempted to effect a single change in a variable and few studies have exposed the subjects to a number of target values which could then be compared. Nonetheless the term optimisation has become widely used.

Studies assessing the effectiveness of specific strategies exists in the following areas

·                 Increasing tissue oxygen delivery

·                 Prevention of myocardial ischaemia

·                 Maintenance of normothermia

·                 Maintenance of normoglycaemia

Increasing Tissue Oxygen Delivery

Tissue hypoperfusion

Maintaining adequate tissue oxygenation reduces morbidity and mortality in critically ill patients⁵. During the perioperative period tissue oxygenation may be impaired as the response to surgery induces alterations to the normal cardiorespiratory and metabolic demands. Hypoxic damage occurs if the oxygen supply demand ratio becomes unbalanced. Tissues especially at risk are the intestine and the kidney, because of their critical oxygen supply. Other organs may be particularly susceptible in individuals with certain pathologies, for example myocardial ischaemia is more likely in the presence of coronary artery disease.

Physiological background

It is not practical in most clinical situations to directly measure tissue perfusion. As a consequence the surrogate marker of oxygen delivery is commonly used. Oxygen delivery can be increased by raising cardiac output or arterial oxygen content. Oxygen content is derived from the amount of oxygen combined with the haemoglobin molecule (Hueffner constant 0.134 g/liter) and the oxygen dissolved in the blood (partial pressure of oxygen in kPa multiplied by 0.023).

Manipulation of oxygen delivery

Raising the haemoglobin level will produce an overall increase in oxygen delivery. However, this theoretically beneficial effect will be partially offset by the impaired flow characteristic of blood with a higher viscosity.  Provided that the patient has oxygen saturation in the normal range an increased FiO₂ only raises the oxygen delivery by a small amount through the additionally dissolved oxygen. In turn cardiac output consists of the product of stroke volume and heart rate. The stroke volume directly depends on contractility and, according to Starling’s law, on ventricular filling pressure of the heart. Fluids administered as crystalloids, colloids or blood, increase the cardiac output by raising the ventricular preload. Pharmacological therapies with inotropes, vasodilators or drugs combining these two properties are in use to manipulate the cardiovascular system. Vasodilators improve tissue perfusion by reversing vasoconstriction and increases cardiac output by reducing afterload. The effects on tissue perfusion of these drugs may also be negative as they alter regional perfusion and may divert away oxygen from areas of demand. In addition organ perfusion may be lowered secondary to their blood pressure lowering properties. Inotropic drugs raise stroke volume and cardiac output by increasing the force of cardiac muscle contraction. Most inotropic drugs also increase myocardial oxygen consumption and heart rate, allowing less time for myocardial perfusion during the shortened diastole and as a consequence the risk of myocardial ischaemia is increased.

Monitoring

Traditionally pulmonary artery catheters have been used to monitor the oxygen delivery during the manipulation of cardiovascular parameters. Recently the use of pulmonary artery catheters has declined as they have been shown not to improve outcome and may be associated with increased mortality^6,7. In addition, preoperative care for several hours involving intense monitoring and frequent adjustments of fluids and inotropes is not practical in most institutions.  Lack of ITU beds, insufficient time prior to surgery and lack of personnel all probably contribute to this. Alternative non-invasive monitors to measure perfusion such as oesophageal doppler, lithium dilution techniques and gastric tonometry have been advocated.

Evidence for increasing oxygen delivery

Improving oxygen delivery in critically ill patients is associated with an improved outcome. Much of the original work was carried out over 20 years ago but the evidence to support this is still accumulating. A problem with many of the intensive care studies was that they were relatively late interventions. By the time patients were admitted to intensive care they often had multiple organ dysfunction and the interventions in intensive care were instituted when tissue oxygen delivery had been severely impaired for some time. As a result the pathophysiological changes were often irreversible and despite aggressive therapy mortality remained high. In contrast intervention studies that have increased oxygen delivery early during a patient’s illness prior to the onset of multiorgan failure, frequently during the perioperative period, have shown benefits.

Optimisation with fluids and inotropes/dilator

Several investigators have optimised high-risk surgical patients with a combination of fluids and inotropes. Their results have demonstrated a dramatic fall of mortality in the intervention group with number needed to treat (NNT) between four and eight. It is impossible to say if the effects of fluids and inotropes are synergistic or if the beneficial effect of one intervention counteracts the adverse effects of the other. The details of these trials are shown in table 1.

Table 1  Randomised controlled trials testing the effect of perioperative optimisation on 30-day mortality. 

Definitions of abbreviations

El = elective, Em = emergency, # NOF = fractured neck of femur,

PAC = pulmonary artery catheter, NNT = number needed to treat to save one life, NNH = number needed to harm to loose one life, inf = infinity, CI = confidence interval, * 60-day mortality

Shoemaker used fluids, inotropes and vasodilators to achieve supranormal goals of cardiac output (>4.5 l.min^-1.m² ) oxygen delivery (>600 ml.min^-1) and oxygen consumption (>170 ml.min^-1). They reported a mortality of 33% in the control group compared with 4% in the protocol group⁸. Criticisms of this paper include the randomisation procedure, blinding and case mix differences between the two groups. Fluids and dopexamine used to increase oxygen delivery to above 600 ml.min^-1 in high-risk surgical patients reduced mortality from 22.2% 5.7 %⁹. In major elective high-risk procedures optimisation using fluids and inotropes reduced 30-day mortality from 17% to 3%. This paper has been criticised for the high mortality of the control group whose standard of postoperative care may have been lower on the ward in comparison to patients in the intervention group admitted to the intensive care unit¹⁰. In a more recent trial 412 patients undergoing major abdominal surgery received fluids and dopexamine or placebo. Although the subgroup of patients undergoing emergency surgery had a reduced mortality in the intervention group, overall analysis did not demonstrate a beneficial effect¹¹.

Optimisation with fluids alone

Optimisation with fluids alone demonstrated a faster recovery and reduced complication rate. There is no evidence that this strategy in the absence of inotropes reduces mortality, as there is no adequately powered study published.

In elective cardiac surgery oesophageal doppler monitoring was used to guide colloid administration. The protocol group spent a reduced mean number of days in hospital and intensive care and had fewer complications¹². Intraoperative fluid optimisation guided by  oesophageal doppler monitoring in patients presenting for repair of fractured neck of femur reduced the length of hospital stay by 39% ¹³.

Prevention Of Myocardial Ischaemia

Cardiac events such as myocardial infarction or cardiac death are common complications of surgery, occurring in 1% to 5% of unselected patients undergoing non-cardiac surgery and are associated with markedly increased mortality¹⁴. Myocardial ischaemia occurs if myocardial oxygen demand exceeds oxygen supply. Beta-blocking agents reduce myocardial oxygen consumption mainly by reducing heart rate, allowing longer perfusion during diastole, and cardiac inotropy.

Evidence

Two studies have reported significant improvement in patients undergoing major non-cardiac surgery because of perioperative beta-blockade. In patients who received atenolol perioperatively a reduced mortality at two years occurred in the intervention group. Concerns about the validity of this study were raised because confounding factors such as frequency of coronary artery disease, therapy with angiotensin-converting enzyme inhibitors, and discontinuation of postoperative beta-blockade were not well matched between the groups¹⁵. In another study high-risk patients undergoing vascular surgery received bisoprolol or placebo. The frequency of cardiac death or non-fatal myocardial infarction was 34% in the control group versus 3.4% in the intervention group¹⁶. 

 Table 2  Randomised controlled trials testing the effect of perioperative beta-blockade on mortality.

Definitions of abbreviations

El = elective, NNT = number needed treat to reduce incidence of endpoint by 1, CI = confidence interval

Although it would therefore appear that patient at risk of myocardial ischaemia benefit from perioperative beta-blockade a number of questions remain unanswered. Do only high-risk patients benefit from this approach or should low risk patients also receive beta-blockers? When should beta-blocker therapy be started and for how long continued? The evidence for these question is less clear but it is likely that beta-blockade should be continued beyond hospitalisation if it is tolerated well. It is also unclear which patients should be optimised using fluids and inotropes and which should be beta-blocked. Although these two approaches appear contradictory they may not be always mutually exclusive. Patients with coronary artery disease presenting for major surgery will benefit from reducing myocardial work but their outcome may also be improved by optimising their circulating volume and afterload.

Maintenance Of Normothermia

Physiology

Normal body temperature is 37º C and thermoregulatory mechanisms control this temperature tightly with a standard deviation of about 0.2º C. Perioperative hypothermia, defined as a body core temperature < 35º C, is a serious occurrence during anaesthesia and surgery. Anaesthesia may induce hypothermia through a number of different mechanisms. Firstly behavioural responses, normally enabling the individual to control their environment are abolished. Secondly cutanous vasoconstriction is antagonised by vasodilator anaesthetics. Furthermore thermoregulatory thresholds are displaced from normal temperature. Particularly the hypothermic threshold is lowered by 3-4º C and thus the thermoregulatory response to heat loss is impaired.

Evidence

The effect of perioperative hypothermia on outcome has been studied in a number of randomised controlled trials (table 3). Hypothermia not only induces postoperative shivering and delays recovery from the anaesthetic¹⁷ but also increases blood loss during hip arthroplasty leading to a seven-fold increase in transfusion rate¹⁹. Kurz demonstrated a threefold increase in wound infection rate and prolonged hospital stay in hypothermic patients undergoing colonic surgery²⁰. Cardiac event following body cavity surgery in patients with cardiac risk factors were significantly reduced in the normothermic group²¹.

Table 3 Randomised controlled trials testing the effect of perioperative hypothermia on postoperative morbidity. 

Definitions of abbreviations

NNT = number needed treat to reduce incidence of endpoint by 1, CI = confidence interval

Control Of Blood Glucose

Hyperglycemia associated with insulin resistance is common in critically ill patients, even those who have not previously had diabetes. It has been reported that pronounced hyperglycemia may lead to complications in such patients²². The mortality of patients following major surgery was significantly reduced (NNT 29, 95% CI 18 to 95) if the blood glucose was tightly controlled  (4.4 mmol/l – 6.1 mmol/l) compared to conventional insulin therapy (10-11.1 mmol/l)²³. This study mainly included cardiac surgical patients but the result can probably be applied to other high-risk surgical patients susceptible to develop sepsis and multiorgan failure. It would therefore appear prudent to control perioperative glycaemia more tightly than currently practised.

Conclusion

Well-conducted anaesthetic and surgical care, including the maintenance of normothermia, will improve patient’ outcome following major surgery. In addition a small group of high-risk surgical patients benefits from specific optimisation strategies during the perioperative period. The practical conduct of these interventions requires significant investment of time and resources. In face of increasing evidence that outcome can be improved these interventions should be widely employed.

Bibliography

1.        NHS Performance Indicators 2002.: Internet communication: http://www.doh.gov.uk/hes/tables/tb00401e.xls

 2.        Ball J Rhodes A, Bennett ED. Reducing the morbidity and mortality of high risk surgical patients. Yearbook of Intensive Care and Emergency Medicine 2000; 331-42.

 3.        Harten, J.McCreath B,  McMillan D, McArdle C,  Kinsella J. Influence of Social Deprivation on Post-Operative Survival after Emergency Laparotomy.  Anesthesiology 2001; 95:A1113.

 4.        Cook TM, Britton DC, Craft TM, Jones CB, Horrocks M. An audit of hospital mortality after urgent and emergency surgery in the elderly. Annuals of  Royal  College of Surgeons in England 1997;79:361-7.

 5.        Shoemaker Wc, Montgomery ES, Kaplan E et al. Physiologic patterns in surviving and nonsurviving shock patients. Use of sequential cardiorespiratory variables in defining criteria for therapeutic goals and early warning of death. Archives of Surgery 1972; 106:630-636.

 6.        Sandham JD, Hull RD, Brant RF, Knox L, Pineo GF, Doig CJ et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. New England Journal of Medicine 2003; 348:5-14.

 7.        Connors AF, Speroff T, Dawson NV, Thomas C, Harrell FEJ, and Wagner D. The effectiveness of right heart catheterization in initial care of critically ill patients. Journal of American Medical Association 1996; 276:889-897.

 8.        Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS. Prospective trial of supranormal values for survivors as therapeutic goals in high-risk surgical patients. Chest 1988; 94:1176-1186.

9.        Boyd O, Grounds M, Bennett D. A randomized clinical trial of the clinical effect of deliberate increase of oxygen delivery on mortality in high-risk surgical patients. Journal of American  Medical Association 1993; 270:2699-2707.

 10.    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. British Medical Journal 1999;
318:1099-1103.

 11.    Takala J, Meier-Hellmann A, Eddleston J, Hustaert P, Sramek V. Effect of dopexamine on outcome after major abdominal surgery: A prospective, randomized, controlled multicentre study. Critical Care Medicine 2000; 28:3417-3423.

 12.    Mythen M, Webb A. Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Archives of Surgery 1995; 130:423-429.

 13.    Sinclair S, James S, Singer M. Intraoperative intravascular volume optimisation and length of hospital stay after proximal femoral fracture: randomised controlled trial. British Medical Journal 1997; 315::909-912.

 14.    Ashton CM, Petersen NJ, Wray NP, et al. The incidence of perioperative myocardial infarction in men undergoing noncardiac surgery. Annuals of  Internal Medicine 1993; 118:504-510.

 15.    Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. New England Journal of Medicine 1996; 335:1713-20.

 16.    Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD.et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. New England Journal of Medicine 1999;  341:1789-94.
17.    Lenhardt R, Marker E, Goll C, Tschernich H, Kurz A, Sessler DE et al .Mild intraoperative hypothermia prolongs postanaesthetic recovery. Anesthesiology 1997; 87:1318-1323.

 18.    Kurz A, Sessler DI, Narzt E et al. Postoperative hemodynamic and thermoregulatory consequences of intraoperative core hypothermia. Journal of  Clinical  Anesthesiology 1995; 7:359-66.

 19.    Schmidt H, Kurz A,Sessler DI, Kozek S. Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty. The Lancet 1996; 347:289-292.

 20.    Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical wound infection and shorten hospitalisation. The New England Journal of Medicine1996; 334:1209-1215.

 21.    Frank SM, Fleischer LA, Breslow MI, Higgins MS, Olson K, Kelly S et al. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. Journal of the American Medical Association 1997; 277:1127-1134.

 22.    Shangraw RE, Jahoor F, Miyoshi H et al. Differentiation between septic and postburn insulin resistance. Metabolism 1989; 38:983-989.

 23.    van den Berghe G.,Wouters P, Weekers F, Verwaest C, Bruyninck F, Schetz M et al. Intensive insulin therapy in the critically ill patients. New England Journal of Medicine 2001; 345:1359-67.

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