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Optimisation of oxygenation and tissue perfusion in surgical patients
Focus on: Aspects of Critical Care
Optimisation of oxygenation and tissue perfusion in surgical patients夽 O. Boyd
Surgical patients with limited cardiovascular reserve have much worse prognosis than patients with normal hearts. This review identifies 17 randomised controlled clinical trials that have investigated peri-operative therapy designed to increase tissue perfusion in surgical patients, many of whom have limited cardiovascular reserve. Although there are differences which make equating the trials complex, a total of 1974 patients have been enrolled in the studies and the odds ratio for reduction in mortality is 0.45 (95% confidence intervals 0.33–0.60). Further research needs to be undertaken in the identification of patients with limited cardiovascular reserve and for investigating proposed treatment strategies. Despite this, it appears that such patients have improved outcome if they are admitted to intensive care unit pre-operatively and have suitable therapy given to improve tissue oxygen delivery. © 2003 Elsevier Science Ltd. All rights reserved. KEYWORDS: Surgery; Mortality; Intensive care; Echocardiography; Doppler perfusion; Regional catheterization; Swan-Ganz.
Introduction
O. Boyd, The General Intensive Care Unit, Royal Sussex County Hospital, Eastern Road, Brighton BN2 5BE, UK. Tel: +44 (0) 127 369 6955, ext. 4274; E-mail: owen. [email protected] (Requests for offprints to OB)
Surgery and anaesthesia have developed the joint principles of minimising tissue trauma and supporting tissue perfusion. Anaesthetic teaching emphasises resuscitation, monitoring, fluid therapy, temperature control, and better control of post-operative pain and, in certain circumstances, such as aortic surgery, the use of vasodilators and inotropes specifically to maintain perfusion during severe cardiovascular stress. As there is little direct evidence for the effectiveness of any one 夽 This article was originally published in Current Anaesthesia & Critical Care, Volume 13 (2002), issue 4, pages 206–214, original doi:10.1054/cacc.2002.0405. This article is republished with permission from the author.
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particular measure, most anaesthetists rely on personal preference at worst and anecdote at best. Cardiovascular monitoring is usually by use of heart rate and blood pressure measurements which, while easily accessible, provide no information on blood flow and tissue perfusion. It results in the same routine being used for all patients having similar operations, and this may not provide appropriate care. Many cardiovascular factors could theoretically be treated in the peri-operative period, but this requires critical care facilities and an extension of monitoring and treatment regimens, and doubts remain about the usefulness and applicability of this approach. This article reviews the background to the concept of specific targeted improvement in tissue oxygenation in the peri-operative
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period and reviews the literature of studies concerning outcome in this area.
The use of critical care facilities There is plenty of evidence that maintaining adequate tissue perfusion improves post-operative outcome. This more aggressive and targeted approach frequently requires the use of intensive care (ICU) facilities which facilitates the use of more complicated and regulated therapy. • Staffing levels on intensive care are greater than on the rest of the hospital. Although nursing levels vary in different countries, there are frequently nursing ratios of one nurse to one patient or greater. Medical and paramedical personnel are also more readily available in an ICU. • The availability of complicated monitoring equipment may allow more accurate and complicated monitoring to be undertaken than on a general ward which may allow more understanding of the patients current condition and an earlier degree of warning of a deterioration in the patient’s condition. • The availability of other high-technology resources, such as drug infusion pumps, ventilators and specialised cushion beds may allow more accurate titration of therapy and prevent secondary complications. The assessment of the usefulness of ICU therapy in any individual patient is conjecture as no controlled trial will ever now be conducted, but it is certain that complications can arise with post-operative care that might have been prevented by early ICU therapy (Lee et al., 1998). Conversely, intensive care therapy has only limited availability to all patients due to resource and cost considerations, but this limitation may have been overstated. It is also logical to concentrate resources on the higher risk patient and on those in whom outcome can be more favourably effected.
Surgical mortality rates Surgical mortality is considered acceptable at about the 2% level, although there are a number of features which make interpretation
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Table 1 Reasons for difficulty interpreting mortality rates • Figures are often published from major referral centres • There are differing criteria for analysing the causation of post-operative deaths • There are widespread variations in patients considered for different operations and this continually varies over time • Published figures usually do not take into account the influence of co-morbidity
difficult (Table 1). The National Confidential Enquiry into peri-operative deaths in England and Wales 1992–1993 showed that there were 19,861 deaths post-operatively in the year in question, with the median day of death being day 6 (Campling et al., 1995). While this is an overall figure, it is apparent that there are wide variations in mortality depending on what operation is being performed and the underlying condition of the patient. Patients with non-elective admissions (mortality rate 30% vs. 5% for elective admissions), ASA grade 3+ (mortality rate 27% vs. 8% for ASA <3), age over 75 (mortality rate 20% vs. 11% for patients aged 65–74) and major surgery (mortality rate 25% vs. 10% for non-major surgery) are associated with much higher mortality (Edwards et al., 1996), and other studies have shown similar results (Fowkes et al., 1982; Mella et al., 1997; Cook & Day, 1998).
The identification of high-risk patients and the importance of limited physiological reserve Review of the literature also shows that there is a preponderance of investigations concerning the identification of the risk of a cardiac event in the post-operative period. However, this only provides a one-dimensional view of the patient’s risk and may not be entirely appropriate as most high-risk surgical patients who die do so from multiple-organ dysfunction syndrome (MODS) (Deitch, 1993), rather than a distinct cardiac cause. There are a number of factors which acting independently or in combination trigger the onset of MODS (Livingston et al., 1995), one of these factors appears to be alterations in microcirculatory flow (Kirkpatrick et al., 1996; Fry, 1992). There
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Optimisation of oxygenation and tissue perfusion in surgical patients
is also evidence of microvascular injury in patients dying of MODS (Nuytinck et al., 1988), the inadequate oxygen supply to the tissues leading directly to cell death and reperfusion may cause continuation and amplification of the tissue damage (Granger, 1988). There are a number of influences that can effect tissue perfusion around the time of surgery (Boyd, 1997), but one is limited physiological reserve. The data presented above show that a patient most likely to die in the post-operative period is old, an emergency, presenting with co-existing cardiovascular, renal or hepatic impairment and these factors are more important than the type of surgery (Ferguson et al., 1997). For example, age is known to effect the hepatic acute phase response and despite normal baseline function, on days 1 and 2 post-operatively, elderly patients after abdominal surgery had evidence of reduced hepatic perfusion (Suttner et al., 2001). Evidence shows that mortality for elderly patients undergoing non-cardiac surgery is more related to patients related factors, such as a history of cardiac disease and signs of low cardiac output around the time of surgery, than surgery-related factors, such as the type of operation performed (Wirthlin & Cambria, 1998). The principle of physiological reserve is shown in Fig. 1. Baseline requirements are relatively unchanged throughout life, but in older patients reserve is much reduced. Co-existing disease will exaggerate the effects of ageing. For example, a myocardial
Fig. 1 Schematic diagram showing changes in physiological reserve related to ageing. Although baseline function may not change appreciably, the response to a physiological stress is severely limited. Because of the unchanged baseline function, these patients may be difficult to identify.
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infarction might result in more limited cardiovascular reserve in a 50-year-old, than in a 70-year-old without cardiac problems. As we will explore below, surgery and anaesthesia give a unique challenge to all physiological systems and if reserve is not adequate organ failure will result. The failure may be to a single organ, e.g. renal failure, or may be multiple. Both, however, result in increased morbidity and mortality. One major type of dysfunction is that affecting tissue perfusion.
Tissue perfusion and surgical outcome It has been recognised for many years that there are changes in tissue perfusion at the time of life-threatening illness (Cournand et al., 1943), and this is also true of the peri-operative period (see Fig. 2). Observational studies of patients undergoing cardiac surgery have shown that those with cardiac index (CI) greater than 2.4 l/minute/m2 had no serious cardiovascular complications, while those who had lower CI had a mortality rate of 67% (Boyd et al., 1959). More detailed studies showed that patients who survived major non-cardiac surgery had higher CI, lower systemic vascular resistance (SVR), and higher oxygen consumption index (VO2 I) than non-survivors (Shoemaker et al., 1973). Furthermore, it was found that the commonly monitored vital signs, heart rate, temperature, central venous pressure and haemoglobin were the poorest predictors of mortality, while perfusion-related variables, such as CI and total body oxygen delivery (DO2 I) were the best (Shoemaker et al., 1993). The maintenance of tissue perfusion is a vital part of post-operative survival. There are two main pathological processes that inhibit cardiac function in the peri-operative period, ischaemia and ‘pump failure’ caused by inadequate pre-load and myocardial cell dysfunction. Traditionally, the emphasis has been on ischaemia as the major influence in post-operative cardiac problems. This is probably because the pathological changes, such as myocardial infarction, could be relatively easily identified and because monitoring for ischaemic events was thought to be good with the use of peri-operative ECG
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Fig. 2 Flow chart of the causes of MODS showing the pivotal position of reduced tissue perfusion and the vicious circle that this engenders.
recording and the development of continuous ST segment analysis. More recently, the importance of inadequate cardiac filling and inflammation as important causes of peri-operative myocardial dysfunction have been recognised. The importance of understanding all these influences is that therapy can be directed in a rational way to each of them. Good peri-operative cardiac function is vital to maintain tissue perfusion in the peri-operative time.
Cardiovascular optimisation in the peri-operative period Tissue perfusion and cardiovascular optimisation are dependent on adequate blood volume, vasodilation and lack of vasoconstricting influences, correct functioning of physiological control mechanisms at organ and total body level, suitable haemoglobin for
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maximal oxygen carriage, high oxygen saturation, high cardiac output, and the limitation of excessive energy requirement above the ability of flow and oxygen supply to meet it. The last point is particularly important and is usually related to cardiac performance where increasing heart rate and myocardial muscle work is only sustainable if there is adequate coronary artery flow. The philosophical approach to ‘cardiovascular optimisation’ is shown in Fig. 3. The total perfusion, usually assessed as DO2 I, is likened to a reservoir of availability so that changing requirements of organ systems can be met seamlessly and without a lag phase while a response to increased need is met. For any individual organ system, and indeed for the whole body, it may be difficult or impossible to demonstrate a change in requirements, usually assessed as a change in oxygen consumption.
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Optimisation of oxygenation and tissue perfusion in surgical patients
Fig. 3 Diagrammatic representation of the reservoir of available ‘oxygen delivery’. The different houses represent different organ systems. As requirements change, this is continuously matched by the supply if the ‘reservoir’ is kept at a suitable level.
The options for assessing tissue perfusion in a clinical situation are limited, and most studies have concentrated on assessments of total body perfusion based on CI or parameters derived from it. Most studies have used right heart catheterisation to measure CI and derive further parameters, such as DO2 I. Doppler assessment of CI has also been used, and other techniques, such as echocardiography, lithium dye dilution and even formalised clinical estimation, could also be employed. Although most studies have focused on increase of CI, it is unclear which of the components of the equation should be specifically increased. Nor is it known which of the components that influence CI, cardiac filling pressures, the reduction of cardiac afterload, or the increasing cardiac pump power is the most beneficial. It is difficult to assess which patients may benefit most from cardiovascular optimisation, information is lacking and there are as yet no formal scoring systems that have been shown to be useful in this situation. The uses of a single operation type to identify patients or a more general list of clinical characteristics are open to criticism. The first may miss some patients
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and include others that are at not so high risk, the second is open to individual interpretation. Any new policy that is to be implemented in modern healthcare needs to be considered in terms of its influence on resources. Cardiovascular optimisation will initially require more time, more beds, greater skill mix, and suitable post-operative facilities. This appears to be a big commitment and although some studies have started to investigate this point, there is inadequate emphasis on the positive influence that cardiovascular optimisation could have on resource use.
The studies This paper has identified 17 studies in the published literature that have specifically aimed to increase tissue perfusion with fluids, vasodilators or inotropes and then compared the results to a randomly allocated control group. These are summarised in Table 2. The first identified study was published by Schultz et al. (1985). They studied 70 patients undergoing operative repair of hip fracture, showing that compared to a control group with a mortality of 29%, a monitored group
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Study
Criteria for study admission
Schultz et al. (1985)
Fractured neck of femur
Shoemaker et al. (1988)
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Target for treatment in all patients
Target for treatment in the ‘protocol’ group
Odds ratio for reduction in mortality (95% CI)
70
Routine care
0.07 (0.01–0.61)
List of high-risk criteria for general surgical patients
58
Berlauk et al. (1991)
Limb salvage arterial surgery
89
PA catheter used. PAOP 4–12 mmHg and DO2 I 400–550 ml/minute/m2 using fluids, vasodilators and inotropes Routine care as directed by the anaesthesiologist, PA catheter only for in some patients
Fleming et al. (1992)
Trauma-specific diagnostic criteria
67
Boyd et al. (1993)
List of high-risk criteria for general surgical patients Trauma-specific diagnostic criteria
107
General ‘optimised’ physiological profile. Fluid, vasodilators and inotropes used CI >4.5 l/minute/m2 , DO2 I >600 ml/minute/m2 , VO2 >4170 ml/minute/m2 using fluids, vasodilators and inotropes CI >2.8 l/minute/m2 , PAOP 8–15, SVR <1100 dyn second/cm5 . Analysis is based on treatment groups combined vs. control CI >4.52 l/minute/m2 , DO2 I >670 ml/minute/m2 , VO2 I >166 ml/minute/m2 using fluid in fusion and dobutamine if targets not met DO2 I >600 ml/minute/m2 using dopexamine CI >4.5 l/minute/m2 , DO2 I >600 ml/minute/m2 , VO2 I >170 ml/minute/m2 Maximise SV and rise CVP by 3 mmHg with fluid challenges (200 ml hydroxethyl starch) assessed by oesophageal Doppler DO2 I >600 ml/minute/m2 and/or VO2 I >150 ml/minute/m2 using fluid therapy and dopamine or dobutamine if targets not met
Not able to calculate
Bishop et al. (1995)
N
115
Mythen and Webb (1995)
Elective cardiac surgery
60
Durham et al. (1996)
Trauma-specific diagnostic criteria
58
Conventional resuscitation criteria using CVP 8–12 mmHg or PAOP 8–12 mmHg
All patients had PA catheter, PAOP 12–14 mmHg SBP >120, HR <110, UO 30–50 ml/hour. If measured CVP 8–12 mmHg, PAOP 8–12 mmHg Routine care
Routine care, but patients monitored with a PA catheter
0.07 (0.01–0.63)
0.14 (0.01–1.65)
0.41 (0.14–1.15)
0.21 (0.06–0.79) 0.38 (0.16–0.90)
1.17 (0.22–6.33)
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176 Table 2 Randomised, controlled studies of peri-operative intensive care therapy
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Infrarenal aortic reconstruction, lower limb revascularisation
104
Routine care as directed by the anaesthesiologist, PA catheter only for some patients Maintenance intravenous fluid therapy. Oesophageal Doppler used for monitoring, otherwise routine care PA catheter used, only maintenance intravenous fluids given
Sinclair et al. (1997)
Fractured neck of femur
40
Ziegler et al. (1997)
Aortic reconstruction, limb salvage surgery
72
Ueno et al. (1998)
Partial hepatectomy for hepatocellular carcinoma
34
Routine care, including CI 2.8–4.0 l/minute/m2
Valentine et al. (1998)
Aortic surgery
120
Routine care without PA catheters
Wilson et al. (1999)
List of surgical or medical criteria for general surgical patients
138
Routine care
Polonen et al. (2000)
Elective cardiac surgery
393
Routine care
PAOP 8–14 mmHg, CI >2.8 ml/minute/m2 , SVR 1100 dyn second/cm5
1.04 (0.06–17.08)
Maximise SV and increase corrected flow time 40.35 seconds assessed by oesophageal Doppler with fluid challenges PAOP >12 mmHg, SvO2 >65% using fluid boluses, vasodilators and dobutamine CI >4.5 l/minute/m2 , DO2 I >600 ml/minute/m2 , VO2 I >170 ml/minute/m2 PA catheters placed in protocol patients, CI >2.8 l/minute/m2 , PAWP 8–15 mmHg, SVR <1100 dyn second/cm5 PAOP <12 using human albumin 4.5%, DO2 I >600 ml/minute/m2 using fluids, and adrenaline (n = 92) or dopexamine (n = 92). Analysis is based on treatment groups combined vs. control Patients had PA catheterisation, SvO2 >70%, serum lactate <2 mmol/l
0.47 (0.04–5.69)
1.97 (0.31–12.54)
Not able to calculate 3.11 (0.31–30.73)
0.16 (0.04–0.64)
0.38 (0.08–1.81)
Optimisation of oxygenation and tissue perfusion in surgical patients
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Bender et al. (1997)
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Table 2 (Continued )
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Study
Criteria for study admission
Takala et al. (2000)
List of surgical or medical criteria
Lobo et al. (2000)
List of surgical or medical criteria
Total
N
Target for treatment in all patients
Target for treatment in the ‘protocol’ group
Odds ratio for reduction in mortality (95% CI)
412
Haemodynamic stabilisation
0.84 (0.45–1.57)
37
Patients monitored with a PA catheter. Treatment to PAOP 12–16 mmHg using fluids, and DO2 I 520–600 ml/minute/m2 using dobutamine
No specific additional targets. Dopexamine given in two pre-defined doses. Analysis is based on treatment groups combined vs. control Supranormal values of DO2 I <600 ml/minute/m2 using additional dobutamine
1974
0.33 (0.07–1.65)
0.45 (0.33–0.60)
Note: PA = pulmonary artery, PAOP = pulmonary artery occlusion pressure, DO2 I = oxygen delivery index, VO2 I = oxygen consumption index, CI = cardiac index, SVR = systemic vascular resistance, CVP = central venous pressure, SBP = systolic blood pressure, HR = heart rate, UO = urine output, SV = stroke volume, SvO2 = mixed venous oxygen saturation.
Optimisation of oxygenation and tissue perfusion in surgical patients
treated with fluids, inotropes and vasodilators and with a previously identified physiological profile, including increased CI, had a mortality of only 2.9%. Schultz et al. (1985) used a pulmonary artery catheter (PA catheter), and other investigators have also used this technique studying groups of general surgical patients (Shoemaker et al., 1988; Boyd et al., 1993; Wilson et al., 1999; Lobo et al., 2000; Takala et al., 2000), cardiac surgery patients (Polonen et al., 2000), vascular surgery patients (Berlauk et al., 1991; Bender et al., 1997; Ziegler et al., 1997; Valentine et al., 1998) or patients having liver surgery (Ueno et al., 1998). Three studies have investigated patients undergoing surgery following trauma (Fleming et al., 1992; Bishop et al., 1995; Durham et al., 1996). Other investigators do not use PA catheters at all, monitoring blood flows using oesophageal Doppler (Mythen & Webb, 1995; Sinclair et al., 1997). In addition to the mortality and morbidity changes, two studies have the cost implications of treatment targeted to increase tissue perfusion and both have shown decreased cost (Shoemaker et al., 1988; Guest et al., 1997). Furthermore, in the studies investigating treatment targeted to results obtained by PA catheterisation, none have shown increased mortality in the PA catheter groups. This contradicts the widely quoted studies of Connors et al. (1996) and Polanczyk et al. (2001), which showed increased mortality in retrospective studies on critically ill patients who underwent PA catheterisation. Indeed, this review has been unable to find any prospective randomised evidence that confirms these conclusions.
Discussion There have recently been a number of publications reviewing the studies described in this article (Boyd & Bennett, 1996; Forst, 1997; Ivanov et al., 1997; Heyland et al., 1996; Leibowitz & Beilin 1997; Boyd & Hayes, 1999). However, not all of the reviews have primarily addressed issues concerning optimisation of tissue perfusion, concentrating instead on possible effectiveness of right heart catheterisation (Ivanov et al., 1997; Leibowitz & Beilin 1997). Others have included studies
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enrolling patients at a later stage of their illness (Heyland et al., 1996; Boyd & Hayes, 1999) although separating those in the peri-operative period for the purposes of analysis (Boyd & Hayes, 1999). When considering peri-operative patients, Ivanov et al. (1997) gave a combined odds ratio for the studies that they analysed of 0.58 (95% confidence intervals (CI) 0.36–0.94) and Heyland et al. (1996) gave a combined odds ratio of 0.20 (95% CI 0.07–0.55), both reviews including slightly different studies. In the review by Leibowitz and Beilin (1997), no figures were given but they concluded that the right heart catheter did not reduce risk in patients already at low risk, but probably did reduce risk in patients at higher risk particularly high-risk aortic surgery patients. In earlier reviews, Boyd and Hayes (1999) analysed studies that had enrolled a total of 994 patients and showed a combined odds ratio of 0.35 (95% CI 0.23–0.53). A recent analysis using Cochrane methodology, identified 12 published and peer-reviewed papers, which used goal-directed targeting of global flow values peri-operatively, such as oxygen delivery and consumption, stroke volume, lactate and mixed venous oxygen saturation. The papers include 1252 patients with an overall mortality of 6.2%. The mortality in the control group was 56/587 (9.5%) vs. 21/665 (3.2%) in the protocol group, and the Peto odds ratio (CI 95%) was 0.3 (0.19, 0.49) for a reduction in mortality (M.P. W. Grocott, M.A. Hamilton, K. Rowan and the Optimization Steering Group, personal communication). This review identifies 17 randomised, controlled studies that have specifically aimed to increase tissue perfusion in the peri-operative period (Table 2). The studies have enrolled 1974 patients and show a significant reduction in mortality in the treatment group (odds ratio 0.45 (95% CI 0.33–0.60)). Further analysis of the data shows that the studies with higher mortality rate show more improvement in outcome, whereas those with the lowest mortality rates do not. Despite the highly significant results published by all authors who have undertaken combined analyses of studies aiming to improve tissue perfusion around the time of surgery, a number of criticisms of the study techniques have been made. Firstly, studies
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have enrolled differing patient groups and employed different techniques to influence DO2 . Secondly, the studies are not blinded and some have limited statistical power due to low baseline mortality rates and failure to analyse outcome results according to ‘intention to treat’. Thirdly, different endpoints for treatment have been used and both right heart catheterisation and Doppler studies have been used to measure CO. Fourthly, studies vary in their control for co-intervention. And lastly, implementing the proposed techniques on all suitable patients is controversial as it has major implications for peri-operative service provision and some questions remain unanswered. However, peri-operative cardiovascular optimisation in selected groups of patients is shown to reduce mortality. References Bender JS, Smith-Meek MA, Jones CE 1997 Routine pulmonary artery catheterization does not reduce morbidity and mortality of elective vascular surgery: results of a prospective, randomized trial. Annals of Surgery 226(3): 229–236, discussion 236–237 Berlauk JF, Abrams JH, Gilmour IJ, O’Connor SR, Knighton DR, Cerra FB 1991 Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Annals of Surgery 214(3): 289–297, discussion 298–299 Bishop MH, Shoemaker WC, Appel PL et al. 1995 Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation endpoints in severe trauma. Journal of Trauma 38(5): 780–787 Boyd O 1997 Peri-operative cardiovascular optimization: importance and relevance for anaesthesia. British Journal of Hospital Medicine 57(5): 219–223 Boyd O, Bennett ED 1996 Enhancement of peri-operative tissue perfusion as a therapeutic strategy for major surgery. New Horizons 4(4): 453–465 Boyd O, Hayes M 1999 The oxygen trail: the goal. British Medical Bulletin 55(1): 125–139 Boyd AR, Tremblay RE, Spencer FC, Bahnson HT 1959 Estimation of cardiac output soon after intracardiac surgery with cardiopulmonary bypass. Annals of Surgery 150: 613–625 Boyd O, Grounds RM, Bennett ED 1993 A randomized clinical trial of the effect of deliberate peri-operative increase of oxygen delivery on mortality in high-risk surgical patients. The Journal of the American Medical Association 270(22): 2699–2707 Campling EA, Devlin HB, Hoile RW, Lunn JN 1995 The Report of the National Confidential Enquiry into Peri-operative Deaths 1992/1993. NCEPOD, London
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Lee A, Lum ME, O’Regan WJ, Hillman KM 1998 Early postoperative emergencies requiring an intensive care team intervention. The role of ASA physical status and after-hours surgery. Anaesthesia 53(6): 529–535 Leibowitz AB, Beilin Y 1997 Pulmonary artery catheters and outcome in the perioperative period. New Horizons 5(3): 214–221 Livingston DH, Mosenthal AC, Deitch EA 1995 Sepsis and multiple organ dysfunction syndrome: a clinical–mechanistic overview. New Horizons 3(2): 257–266 Lobo SM, Salgado PF, Castillo VG et al. 2000 Effects of maximizing oxygen delivery on morbidity and mortality in high-risk surgical patients. Crititical Care Medicine 28(10): 3396–3404 Mella J, Biffin A, Radcliffe AG, Stamatakis JD, Steele RJ 1997 Population-based audit of colorectal cancer management in two UK health regions. Colorectal Cancer Working Group, Royal College of Surgeons of England Clinical Epidemiology and Audit Unit. British Journal of Surgery 84(12): 1731–1736 Mythen MG, Webb AR 1995 Peri-operative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery. Archives of Surgery 130(4): 423–429 Nuytinck HK, Offermans XJ, Kubat K, Goris JA 1988 Whole-body inflammation in trauma patients. An autopsy study. Archives of Surgery 123(12): 1519–1524 Polanczyk CA, Rohde LE, Goldman L et al. 2001 Right heart catheterization and cardiac complications in patients undergoing noncardiac surgery: an observational study. The Journal of the American Medical Association 286(3): 309–314 Polonen P, Ruokonen E, Hippelainen M, Poyhonen M, Takala J 2000 A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesthesia and Analgesia 90(5): 1052–1059 Schultz RJ, Whitfield GF, LaMura JJ, Raciti A, Krishnamurthy S 1985 The role of physiologic monitoring in patients with fractures of the hip. Journal of Trauma 25(4): 309–316 Shoemaker WC, Montgomery ES, Kaplan E, Elwyn DH 1973 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 106(5): 630–636
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Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS 1988 Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest 94(6): 1176–1186 Shoemaker WC, Appel PL, Kram HB 1993 Hemodynamic and oxygen transport responses in survivors and nonsurvivors of high-risk surgery. Critical Care Medicine 21(7): 977–990 Sinclair S, James S, Singer M 1997 Intraoperative intravascular volume optimization and length of hospital stay after repair of proximal femoral fracture: randomized controlled trial. British Medical Journal 315(7113): 909–912 Suttner SW, Surder C, Lang K, Piper SN, Kumle B, Boldt J 2001 Does age affect liver function and the hepatic acute phase response after major abdominal surgery? Intensive Care Medicine 27(11): 1762–1769 Takala J, Meier-Hellmann A, Eddleston J, Hulstaert P, Sramek V 2000 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. Critical Care Medicine 28(10): 3417–3423 Ueno S, Tanabe G, Yamada H et al. 1998 Response of patients with cirrhosis who have undergone partial hepatectomy to treatment aimed at achieving supranormal oxygen delivery and consumption. Surgery 123(3): 278–286 Valentine RJ, Duke ML, Inman MH et al. 1998 Effectiveness of pulmonary artery catheters in aortic surgery: a randomized trial. Journal of Vascular Surgery 27(2): 203–211, discussion 211–212 Wilson J, Woods I, Fawcett J et al. 1999 Reducing the risk of major elective surgery: randomized controlled trial of preoperative optimization of oxygen delivery. British Medical Journal 318(7191): 1099–1103 Wirthlin DJ, Cambria RP 1998 Surgery-specific considerations in the cardiac patient undergoing noncardiac surgery. Progress in Cardiovascular Diseases 40(5): 453–468 Ziegler DW, Wright JG, Choban PS, Flancbaum L 1997 A prospective randomized trial of preoperative “optimization” of cardiac function in patients undergoing elective peripheral vascular surgery. Surgery 122(3): 584–592
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Optimisation of oxygenation and tissue perfusion in surgical patients夽 O. Boyd
Surgical patients with limited cardiovascular reserve have much worse prognosis than patients with normal hearts. This review identifies 17 randomised controlled clinical trials that have investigated peri-operative therapy designed to increase tissue perfusion in surgical patients, many of whom have limited cardiovascular reserve. Although there are differences which make equating the trials complex, a total of 1974 patients have been enrolled in the studies and the odds ratio for reduction in mortality is 0.45 (95% confidence intervals 0.33–0.60). Further research needs to be undertaken in the identification of patients with limited cardiovascular reserve and for investigating proposed treatment strategies. Despite this, it appears that such patients have improved outcome if they are admitted to intensive care unit pre-operatively and have suitable therapy given to improve tissue oxygen delivery. © 2003 Elsevier Science Ltd. All rights reserved. KEYWORDS: Surgery; Mortality; Intensive care; Echocardiography; Doppler perfusion; Regional catheterization; Swan-Ganz.
Introduction
O. Boyd, The General Intensive Care Unit, Royal Sussex County Hospital, Eastern Road, Brighton BN2 5BE, UK. Tel: +44 (0) 127 369 6955, ext. 4274; E-mail: owen. [email protected] (Requests for offprints to OB)
Surgery and anaesthesia have developed the joint principles of minimising tissue trauma and supporting tissue perfusion. Anaesthetic teaching emphasises resuscitation, monitoring, fluid therapy, temperature control, and better control of post-operative pain and, in certain circumstances, such as aortic surgery, the use of vasodilators and inotropes specifically to maintain perfusion during severe cardiovascular stress. As there is little direct evidence for the effectiveness of any one 夽 This article was originally published in Current Anaesthesia & Critical Care, Volume 13 (2002), issue 4, pages 206–214, original doi:10.1054/cacc.2002.0405. This article is republished with permission from the author.
© 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0964-3397(03)00026-0
particular measure, most anaesthetists rely on personal preference at worst and anecdote at best. Cardiovascular monitoring is usually by use of heart rate and blood pressure measurements which, while easily accessible, provide no information on blood flow and tissue perfusion. It results in the same routine being used for all patients having similar operations, and this may not provide appropriate care. Many cardiovascular factors could theoretically be treated in the peri-operative period, but this requires critical care facilities and an extension of monitoring and treatment regimens, and doubts remain about the usefulness and applicability of this approach. This article reviews the background to the concept of specific targeted improvement in tissue oxygenation in the peri-operative
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period and reviews the literature of studies concerning outcome in this area.
The use of critical care facilities There is plenty of evidence that maintaining adequate tissue perfusion improves post-operative outcome. This more aggressive and targeted approach frequently requires the use of intensive care (ICU) facilities which facilitates the use of more complicated and regulated therapy. • Staffing levels on intensive care are greater than on the rest of the hospital. Although nursing levels vary in different countries, there are frequently nursing ratios of one nurse to one patient or greater. Medical and paramedical personnel are also more readily available in an ICU. • The availability of complicated monitoring equipment may allow more accurate and complicated monitoring to be undertaken than on a general ward which may allow more understanding of the patients current condition and an earlier degree of warning of a deterioration in the patient’s condition. • The availability of other high-technology resources, such as drug infusion pumps, ventilators and specialised cushion beds may allow more accurate titration of therapy and prevent secondary complications. The assessment of the usefulness of ICU therapy in any individual patient is conjecture as no controlled trial will ever now be conducted, but it is certain that complications can arise with post-operative care that might have been prevented by early ICU therapy (Lee et al., 1998). Conversely, intensive care therapy has only limited availability to all patients due to resource and cost considerations, but this limitation may have been overstated. It is also logical to concentrate resources on the higher risk patient and on those in whom outcome can be more favourably effected.
Surgical mortality rates Surgical mortality is considered acceptable at about the 2% level, although there are a number of features which make interpretation
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Table 1 Reasons for difficulty interpreting mortality rates • Figures are often published from major referral centres • There are differing criteria for analysing the causation of post-operative deaths • There are widespread variations in patients considered for different operations and this continually varies over time • Published figures usually do not take into account the influence of co-morbidity
difficult (Table 1). The National Confidential Enquiry into peri-operative deaths in England and Wales 1992–1993 showed that there were 19,861 deaths post-operatively in the year in question, with the median day of death being day 6 (Campling et al., 1995). While this is an overall figure, it is apparent that there are wide variations in mortality depending on what operation is being performed and the underlying condition of the patient. Patients with non-elective admissions (mortality rate 30% vs. 5% for elective admissions), ASA grade 3+ (mortality rate 27% vs. 8% for ASA <3), age over 75 (mortality rate 20% vs. 11% for patients aged 65–74) and major surgery (mortality rate 25% vs. 10% for non-major surgery) are associated with much higher mortality (Edwards et al., 1996), and other studies have shown similar results (Fowkes et al., 1982; Mella et al., 1997; Cook & Day, 1998).
The identification of high-risk patients and the importance of limited physiological reserve Review of the literature also shows that there is a preponderance of investigations concerning the identification of the risk of a cardiac event in the post-operative period. However, this only provides a one-dimensional view of the patient’s risk and may not be entirely appropriate as most high-risk surgical patients who die do so from multiple-organ dysfunction syndrome (MODS) (Deitch, 1993), rather than a distinct cardiac cause. There are a number of factors which acting independently or in combination trigger the onset of MODS (Livingston et al., 1995), one of these factors appears to be alterations in microcirculatory flow (Kirkpatrick et al., 1996; Fry, 1992). There
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Optimisation of oxygenation and tissue perfusion in surgical patients
is also evidence of microvascular injury in patients dying of MODS (Nuytinck et al., 1988), the inadequate oxygen supply to the tissues leading directly to cell death and reperfusion may cause continuation and amplification of the tissue damage (Granger, 1988). There are a number of influences that can effect tissue perfusion around the time of surgery (Boyd, 1997), but one is limited physiological reserve. The data presented above show that a patient most likely to die in the post-operative period is old, an emergency, presenting with co-existing cardiovascular, renal or hepatic impairment and these factors are more important than the type of surgery (Ferguson et al., 1997). For example, age is known to effect the hepatic acute phase response and despite normal baseline function, on days 1 and 2 post-operatively, elderly patients after abdominal surgery had evidence of reduced hepatic perfusion (Suttner et al., 2001). Evidence shows that mortality for elderly patients undergoing non-cardiac surgery is more related to patients related factors, such as a history of cardiac disease and signs of low cardiac output around the time of surgery, than surgery-related factors, such as the type of operation performed (Wirthlin & Cambria, 1998). The principle of physiological reserve is shown in Fig. 1. Baseline requirements are relatively unchanged throughout life, but in older patients reserve is much reduced. Co-existing disease will exaggerate the effects of ageing. For example, a myocardial
Fig. 1 Schematic diagram showing changes in physiological reserve related to ageing. Although baseline function may not change appreciably, the response to a physiological stress is severely limited. Because of the unchanged baseline function, these patients may be difficult to identify.
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infarction might result in more limited cardiovascular reserve in a 50-year-old, than in a 70-year-old without cardiac problems. As we will explore below, surgery and anaesthesia give a unique challenge to all physiological systems and if reserve is not adequate organ failure will result. The failure may be to a single organ, e.g. renal failure, or may be multiple. Both, however, result in increased morbidity and mortality. One major type of dysfunction is that affecting tissue perfusion.
Tissue perfusion and surgical outcome It has been recognised for many years that there are changes in tissue perfusion at the time of life-threatening illness (Cournand et al., 1943), and this is also true of the peri-operative period (see Fig. 2). Observational studies of patients undergoing cardiac surgery have shown that those with cardiac index (CI) greater than 2.4 l/minute/m2 had no serious cardiovascular complications, while those who had lower CI had a mortality rate of 67% (Boyd et al., 1959). More detailed studies showed that patients who survived major non-cardiac surgery had higher CI, lower systemic vascular resistance (SVR), and higher oxygen consumption index (VO2 I) than non-survivors (Shoemaker et al., 1973). Furthermore, it was found that the commonly monitored vital signs, heart rate, temperature, central venous pressure and haemoglobin were the poorest predictors of mortality, while perfusion-related variables, such as CI and total body oxygen delivery (DO2 I) were the best (Shoemaker et al., 1993). The maintenance of tissue perfusion is a vital part of post-operative survival. There are two main pathological processes that inhibit cardiac function in the peri-operative period, ischaemia and ‘pump failure’ caused by inadequate pre-load and myocardial cell dysfunction. Traditionally, the emphasis has been on ischaemia as the major influence in post-operative cardiac problems. This is probably because the pathological changes, such as myocardial infarction, could be relatively easily identified and because monitoring for ischaemic events was thought to be good with the use of peri-operative ECG
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Fig. 2 Flow chart of the causes of MODS showing the pivotal position of reduced tissue perfusion and the vicious circle that this engenders.
recording and the development of continuous ST segment analysis. More recently, the importance of inadequate cardiac filling and inflammation as important causes of peri-operative myocardial dysfunction have been recognised. The importance of understanding all these influences is that therapy can be directed in a rational way to each of them. Good peri-operative cardiac function is vital to maintain tissue perfusion in the peri-operative time.
Cardiovascular optimisation in the peri-operative period Tissue perfusion and cardiovascular optimisation are dependent on adequate blood volume, vasodilation and lack of vasoconstricting influences, correct functioning of physiological control mechanisms at organ and total body level, suitable haemoglobin for
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maximal oxygen carriage, high oxygen saturation, high cardiac output, and the limitation of excessive energy requirement above the ability of flow and oxygen supply to meet it. The last point is particularly important and is usually related to cardiac performance where increasing heart rate and myocardial muscle work is only sustainable if there is adequate coronary artery flow. The philosophical approach to ‘cardiovascular optimisation’ is shown in Fig. 3. The total perfusion, usually assessed as DO2 I, is likened to a reservoir of availability so that changing requirements of organ systems can be met seamlessly and without a lag phase while a response to increased need is met. For any individual organ system, and indeed for the whole body, it may be difficult or impossible to demonstrate a change in requirements, usually assessed as a change in oxygen consumption.
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Optimisation of oxygenation and tissue perfusion in surgical patients
Fig. 3 Diagrammatic representation of the reservoir of available ‘oxygen delivery’. The different houses represent different organ systems. As requirements change, this is continuously matched by the supply if the ‘reservoir’ is kept at a suitable level.
The options for assessing tissue perfusion in a clinical situation are limited, and most studies have concentrated on assessments of total body perfusion based on CI or parameters derived from it. Most studies have used right heart catheterisation to measure CI and derive further parameters, such as DO2 I. Doppler assessment of CI has also been used, and other techniques, such as echocardiography, lithium dye dilution and even formalised clinical estimation, could also be employed. Although most studies have focused on increase of CI, it is unclear which of the components of the equation should be specifically increased. Nor is it known which of the components that influence CI, cardiac filling pressures, the reduction of cardiac afterload, or the increasing cardiac pump power is the most beneficial. It is difficult to assess which patients may benefit most from cardiovascular optimisation, information is lacking and there are as yet no formal scoring systems that have been shown to be useful in this situation. The uses of a single operation type to identify patients or a more general list of clinical characteristics are open to criticism. The first may miss some patients
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and include others that are at not so high risk, the second is open to individual interpretation. Any new policy that is to be implemented in modern healthcare needs to be considered in terms of its influence on resources. Cardiovascular optimisation will initially require more time, more beds, greater skill mix, and suitable post-operative facilities. This appears to be a big commitment and although some studies have started to investigate this point, there is inadequate emphasis on the positive influence that cardiovascular optimisation could have on resource use.
The studies This paper has identified 17 studies in the published literature that have specifically aimed to increase tissue perfusion with fluids, vasodilators or inotropes and then compared the results to a randomly allocated control group. These are summarised in Table 2. The first identified study was published by Schultz et al. (1985). They studied 70 patients undergoing operative repair of hip fracture, showing that compared to a control group with a mortality of 29%, a monitored group
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Study
Criteria for study admission
Schultz et al. (1985)
Fractured neck of femur
Shoemaker et al. (1988)
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Target for treatment in all patients
Target for treatment in the ‘protocol’ group
Odds ratio for reduction in mortality (95% CI)
70
Routine care
0.07 (0.01–0.61)
List of high-risk criteria for general surgical patients
58
Berlauk et al. (1991)
Limb salvage arterial surgery
89
PA catheter used. PAOP 4–12 mmHg and DO2 I 400–550 ml/minute/m2 using fluids, vasodilators and inotropes Routine care as directed by the anaesthesiologist, PA catheter only for in some patients
Fleming et al. (1992)
Trauma-specific diagnostic criteria
67
Boyd et al. (1993)
List of high-risk criteria for general surgical patients Trauma-specific diagnostic criteria
107
General ‘optimised’ physiological profile. Fluid, vasodilators and inotropes used CI >4.5 l/minute/m2 , DO2 I >600 ml/minute/m2 , VO2 >4170 ml/minute/m2 using fluids, vasodilators and inotropes CI >2.8 l/minute/m2 , PAOP 8–15, SVR <1100 dyn second/cm5 . Analysis is based on treatment groups combined vs. control CI >4.52 l/minute/m2 , DO2 I >670 ml/minute/m2 , VO2 I >166 ml/minute/m2 using fluid in fusion and dobutamine if targets not met DO2 I >600 ml/minute/m2 using dopexamine CI >4.5 l/minute/m2 , DO2 I >600 ml/minute/m2 , VO2 I >170 ml/minute/m2 Maximise SV and rise CVP by 3 mmHg with fluid challenges (200 ml hydroxethyl starch) assessed by oesophageal Doppler DO2 I >600 ml/minute/m2 and/or VO2 I >150 ml/minute/m2 using fluid therapy and dopamine or dobutamine if targets not met
Not able to calculate
Bishop et al. (1995)
N
115
Mythen and Webb (1995)
Elective cardiac surgery
60
Durham et al. (1996)
Trauma-specific diagnostic criteria
58
Conventional resuscitation criteria using CVP 8–12 mmHg or PAOP 8–12 mmHg
All patients had PA catheter, PAOP 12–14 mmHg SBP >120, HR <110, UO 30–50 ml/hour. If measured CVP 8–12 mmHg, PAOP 8–12 mmHg Routine care
Routine care, but patients monitored with a PA catheter
0.07 (0.01–0.63)
0.14 (0.01–1.65)
0.41 (0.14–1.15)
0.21 (0.06–0.79) 0.38 (0.16–0.90)
1.17 (0.22–6.33)
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176 Table 2 Randomised, controlled studies of peri-operative intensive care therapy
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Infrarenal aortic reconstruction, lower limb revascularisation
104
Routine care as directed by the anaesthesiologist, PA catheter only for some patients Maintenance intravenous fluid therapy. Oesophageal Doppler used for monitoring, otherwise routine care PA catheter used, only maintenance intravenous fluids given
Sinclair et al. (1997)
Fractured neck of femur
40
Ziegler et al. (1997)
Aortic reconstruction, limb salvage surgery
72
Ueno et al. (1998)
Partial hepatectomy for hepatocellular carcinoma
34
Routine care, including CI 2.8–4.0 l/minute/m2
Valentine et al. (1998)
Aortic surgery
120
Routine care without PA catheters
Wilson et al. (1999)
List of surgical or medical criteria for general surgical patients
138
Routine care
Polonen et al. (2000)
Elective cardiac surgery
393
Routine care
PAOP 8–14 mmHg, CI >2.8 ml/minute/m2 , SVR 1100 dyn second/cm5
1.04 (0.06–17.08)
Maximise SV and increase corrected flow time 40.35 seconds assessed by oesophageal Doppler with fluid challenges PAOP >12 mmHg, SvO2 >65% using fluid boluses, vasodilators and dobutamine CI >4.5 l/minute/m2 , DO2 I >600 ml/minute/m2 , VO2 I >170 ml/minute/m2 PA catheters placed in protocol patients, CI >2.8 l/minute/m2 , PAWP 8–15 mmHg, SVR <1100 dyn second/cm5 PAOP <12 using human albumin 4.5%, DO2 I >600 ml/minute/m2 using fluids, and adrenaline (n = 92) or dopexamine (n = 92). Analysis is based on treatment groups combined vs. control Patients had PA catheterisation, SvO2 >70%, serum lactate <2 mmol/l
0.47 (0.04–5.69)
1.97 (0.31–12.54)
Not able to calculate 3.11 (0.31–30.73)
0.16 (0.04–0.64)
0.38 (0.08–1.81)
Optimisation of oxygenation and tissue perfusion in surgical patients
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Bender et al. (1997)
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Table 2 (Continued )
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Study
Criteria for study admission
Takala et al. (2000)
List of surgical or medical criteria
Lobo et al. (2000)
List of surgical or medical criteria
Total
N
Target for treatment in all patients
Target for treatment in the ‘protocol’ group
Odds ratio for reduction in mortality (95% CI)
412
Haemodynamic stabilisation
0.84 (0.45–1.57)
37
Patients monitored with a PA catheter. Treatment to PAOP 12–16 mmHg using fluids, and DO2 I 520–600 ml/minute/m2 using dobutamine
No specific additional targets. Dopexamine given in two pre-defined doses. Analysis is based on treatment groups combined vs. control Supranormal values of DO2 I <600 ml/minute/m2 using additional dobutamine
1974
0.33 (0.07–1.65)
0.45 (0.33–0.60)
Note: PA = pulmonary artery, PAOP = pulmonary artery occlusion pressure, DO2 I = oxygen delivery index, VO2 I = oxygen consumption index, CI = cardiac index, SVR = systemic vascular resistance, CVP = central venous pressure, SBP = systolic blood pressure, HR = heart rate, UO = urine output, SV = stroke volume, SvO2 = mixed venous oxygen saturation.
Optimisation of oxygenation and tissue perfusion in surgical patients
treated with fluids, inotropes and vasodilators and with a previously identified physiological profile, including increased CI, had a mortality of only 2.9%. Schultz et al. (1985) used a pulmonary artery catheter (PA catheter), and other investigators have also used this technique studying groups of general surgical patients (Shoemaker et al., 1988; Boyd et al., 1993; Wilson et al., 1999; Lobo et al., 2000; Takala et al., 2000), cardiac surgery patients (Polonen et al., 2000), vascular surgery patients (Berlauk et al., 1991; Bender et al., 1997; Ziegler et al., 1997; Valentine et al., 1998) or patients having liver surgery (Ueno et al., 1998). Three studies have investigated patients undergoing surgery following trauma (Fleming et al., 1992; Bishop et al., 1995; Durham et al., 1996). Other investigators do not use PA catheters at all, monitoring blood flows using oesophageal Doppler (Mythen & Webb, 1995; Sinclair et al., 1997). In addition to the mortality and morbidity changes, two studies have the cost implications of treatment targeted to increase tissue perfusion and both have shown decreased cost (Shoemaker et al., 1988; Guest et al., 1997). Furthermore, in the studies investigating treatment targeted to results obtained by PA catheterisation, none have shown increased mortality in the PA catheter groups. This contradicts the widely quoted studies of Connors et al. (1996) and Polanczyk et al. (2001), which showed increased mortality in retrospective studies on critically ill patients who underwent PA catheterisation. Indeed, this review has been unable to find any prospective randomised evidence that confirms these conclusions.
Discussion There have recently been a number of publications reviewing the studies described in this article (Boyd & Bennett, 1996; Forst, 1997; Ivanov et al., 1997; Heyland et al., 1996; Leibowitz & Beilin 1997; Boyd & Hayes, 1999). However, not all of the reviews have primarily addressed issues concerning optimisation of tissue perfusion, concentrating instead on possible effectiveness of right heart catheterisation (Ivanov et al., 1997; Leibowitz & Beilin 1997). Others have included studies
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enrolling patients at a later stage of their illness (Heyland et al., 1996; Boyd & Hayes, 1999) although separating those in the peri-operative period for the purposes of analysis (Boyd & Hayes, 1999). When considering peri-operative patients, Ivanov et al. (1997) gave a combined odds ratio for the studies that they analysed of 0.58 (95% confidence intervals (CI) 0.36–0.94) and Heyland et al. (1996) gave a combined odds ratio of 0.20 (95% CI 0.07–0.55), both reviews including slightly different studies. In the review by Leibowitz and Beilin (1997), no figures were given but they concluded that the right heart catheter did not reduce risk in patients already at low risk, but probably did reduce risk in patients at higher risk particularly high-risk aortic surgery patients. In earlier reviews, Boyd and Hayes (1999) analysed studies that had enrolled a total of 994 patients and showed a combined odds ratio of 0.35 (95% CI 0.23–0.53). A recent analysis using Cochrane methodology, identified 12 published and peer-reviewed papers, which used goal-directed targeting of global flow values peri-operatively, such as oxygen delivery and consumption, stroke volume, lactate and mixed venous oxygen saturation. The papers include 1252 patients with an overall mortality of 6.2%. The mortality in the control group was 56/587 (9.5%) vs. 21/665 (3.2%) in the protocol group, and the Peto odds ratio (CI 95%) was 0.3 (0.19, 0.49) for a reduction in mortality (M.P. W. Grocott, M.A. Hamilton, K. Rowan and the Optimization Steering Group, personal communication). This review identifies 17 randomised, controlled studies that have specifically aimed to increase tissue perfusion in the peri-operative period (Table 2). The studies have enrolled 1974 patients and show a significant reduction in mortality in the treatment group (odds ratio 0.45 (95% CI 0.33–0.60)). Further analysis of the data shows that the studies with higher mortality rate show more improvement in outcome, whereas those with the lowest mortality rates do not. Despite the highly significant results published by all authors who have undertaken combined analyses of studies aiming to improve tissue perfusion around the time of surgery, a number of criticisms of the study techniques have been made. Firstly, studies
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have enrolled differing patient groups and employed different techniques to influence DO2 . Secondly, the studies are not blinded and some have limited statistical power due to low baseline mortality rates and failure to analyse outcome results according to ‘intention to treat’. Thirdly, different endpoints for treatment have been used and both right heart catheterisation and Doppler studies have been used to measure CO. Fourthly, studies vary in their control for co-intervention. And lastly, implementing the proposed techniques on all suitable patients is controversial as it has major implications for peri-operative service provision and some questions remain unanswered. However, peri-operative cardiovascular optimisation in selected groups of patients is shown to reduce mortality. References Bender JS, Smith-Meek MA, Jones CE 1997 Routine pulmonary artery catheterization does not reduce morbidity and mortality of elective vascular surgery: results of a prospective, randomized trial. Annals of Surgery 226(3): 229–236, discussion 236–237 Berlauk JF, Abrams JH, Gilmour IJ, O’Connor SR, Knighton DR, Cerra FB 1991 Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Annals of Surgery 214(3): 289–297, discussion 298–299 Bishop MH, Shoemaker WC, Appel PL et al. 1995 Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation endpoints in severe trauma. Journal of Trauma 38(5): 780–787 Boyd O 1997 Peri-operative cardiovascular optimization: importance and relevance for anaesthesia. British Journal of Hospital Medicine 57(5): 219–223 Boyd O, Bennett ED 1996 Enhancement of peri-operative tissue perfusion as a therapeutic strategy for major surgery. New Horizons 4(4): 453–465 Boyd O, Hayes M 1999 The oxygen trail: the goal. British Medical Bulletin 55(1): 125–139 Boyd AR, Tremblay RE, Spencer FC, Bahnson HT 1959 Estimation of cardiac output soon after intracardiac surgery with cardiopulmonary bypass. Annals of Surgery 150: 613–625 Boyd O, Grounds RM, Bennett ED 1993 A randomized clinical trial of the effect of deliberate peri-operative increase of oxygen delivery on mortality in high-risk surgical patients. The Journal of the American Medical Association 270(22): 2699–2707 Campling EA, Devlin HB, Hoile RW, Lunn JN 1995 The Report of the National Confidential Enquiry into Peri-operative Deaths 1992/1993. NCEPOD, London
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