Patients with cardiac diseases undergoing non-cardiac surgery experience more postoperative problems than other patients [1, 2, 3, 4, 5, 6]. The stress related to surgery increases the neuroendocrine activity and changes the coagulation status of the patient. Arterial hypotension, hypertension and tachycardia accompanied by hypercoagulability may lead to myocardial infarction [7, 8]. The current evidence suggests that myocardial oxygen supply-demand imbalance is of particular importance in the early postoperative period [7]. Flow stagnation and thrombus formation are important pathways in the development of a perioperative myocardial infarction along with perioperative tachycardia [7]. The mortality after non-cardiac surgery has decreased but perioperative myocardial infarction still bears a high risk of death (8.8-29.4%) or leads to a longer postoperative course for the patient and higher cost for society [1, 9, 10, 11] (Table 1).

The prevention of these events is critical. The perioperative team must work as a unit and acknowledge that the work involves preoperative evaluation and optimization, perioperative management and postoperative surveillance and care (Table 2). In difficult patients, the most experienced and qualified personnel should attend and the possibility of reducing the extent of the intervention should be considered [6, 7, 8, 11, 12, 13]. A thorough understanding of the physiology and pathophysiology is vital for a successful outcome. The present paper addresses the current literature in order to summarize the potential means to reduce the incidence of anaesthesia-related perioperative problems.

METHODS

The paper is based on a systematic literature search in Pubmed, major international guidelines and reviews as well as our own clinical experience. There are numerous studies dealing with cardiac patients and non-cardiac surgery but very few are randomized prospective trials with sufficient power to act as a base for good recommendations. The European Society of Anaesthesiology has taken initiative to provide more robust European data for recommendations. At present the international guidelines are mostly based on agreement between experts [11, 12, 13].

PREOPERATIVE EXAMINATIONS AND INTERVENTIONS

Silent myocardial ischaemia can be uncovered by increasing sympathetic drive either through a dobutamine stress test or by a cycling/treadmill test. A normal stress test has a high predictive value for an uncomplicated perioperative course while a positive stress test has less precision in predicting problems [9]. The logic of a positive stress test would be to provide the patient with a cardiac intervention before non-cardiac surgery. Recent studies, however, have demonstrated that there is no benefit of either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for patients with stable angina pectoris [14, 15]. Thus, the indication for stress testing in patients with stable angina is not strong. In fact, the indication for coronary interventions should be seen separate from planned non-coronary surgery, except for high risk surgery where it could be considered [11]. On the other side, patients with unstable angina (nocturnal chest pain, chest pain when seated, low or rapidly changing threshold of chest pain) should have priority for a cardiac intervention since the perioperative risks are very high. Thus, non-cardiac surgery in unstable angina pectoris patients should be performed only on vital indications.

PREOPERATIVE ECHOCARDIOGRAPHY

There are conflicting data about the value of preoperative echocardiography before non-cardiac surgery. There is no evidence for performing preoperative echocardiography unless the symptoms of cardiac disease are present. However, when preoperative beta-blockade is planned, an echocardiogram with special attention to heart failure may be indicated [3, 16].

HEART VALVE DISEASE

Patients with valvular disease are at higher perioperative risk. Planned valve surgery is therefore best done before non-cardiac surgery, if non-cardiac surgery can wait [4, 5, 6]. When delay of surgery is not advisable, non-cardiac surgery can be performed but higher level of monitoring and surveillance is recommended [10, 11].

In everyday life the older patients with previously undiagnosed aortic stenosis may come at night for repair of a fractured hip or other semi-emergency operations when only junior anaesthesiologists and surgeons are present. When given a localized spinal anaesthesia after volume loading and if surgery is uncomplicated the results may be good. However, taking all factors into consideration, proper preoperative evaluation and perioperative management supervised by highly qualified personnel is advisable.

CORONARY STENTS

The frequency of intracoronary stent implantation is increasing and the prevalence in the population rises rapidly. The stents covered with an antithrombotic material, the drug eluting stents (DES) are of special interest. The antithrombotic treatment used to minimize stent thrombosis, called dual platelet inhibition, constitutes a challenge to the anaesthesiologist and surgeon. Clopidogrel, a platelet inhibitor,  has been considered essential to avoid stent thrombosis and up till now it has been common practice to continue clopidogrel for at least 12 months after implantation. Some cardiologists claim that a lifelong treatment is needed [8, 17, 18, 19] while the recent study did not find increased stent thrombosis when clopidogrel was stopped after one year [19].

Patients treated with platelet inhibitors require special focus on surgical haemostasis, particularly that a small haematoma can cause major harm such as in neurosurgery. The surgical team has to know the type of stent used and plan the management together with the relevant specialists. In emergency surgery, specialists such as haematologist and cardiologist may be consulted [18]. When coronary intervention (e.g. PCI) is planned before non-cardiac surgery bare-metal stents should be used as these seem to be less liable to thrombosis when platelet inhibitors are stopped. Whenever possible, it is recommended to wait for a period of three months before non-cardiac surgery, though the documentation for such recommendations is scarce (Table 3).

PREOPERATIVE MEDICATION

Beta-blockers

Beta-blockers have been used in the perioperative setting for more than thirty years. Frequently cited randomized studies have increased their use despite serious objections to the design and the results [20, 21]. The popularity of beta-blockers is partly based on the logic of their use since stress reduction during surgery has been a mantra in perioperative management.

Two major studies, the Dipom study from Denmark including 921 diabetic patients and the international POISE study including 8351 patients from several countries have questioned the rationale behind this treatment [22, 23]. The two studies were well powered having the number of included patients that is rarely seen in perioperative care and involving patients that had been reckoned to be at high risk. The Dipom study did not find any advantages of giving preoperative beta-blockade to patients with diabetes as a risk factor. The POISE study showed that preoperative beta-blockade was associated with a reduction in the number of cardiac problems. In contrast, at 30-day follow-up there was an increase in cerebral insults (1.0% in the beta-blocked group compared to 0.5% in controls) and increased mortality (3.1% vs 2.3%). When these two major randomized studies came out negative, they tended to shift the general attitude.

Poldermans and his group [24, 25] have a long record in evaluating the use of perioperative beta-blockers and commented critically on the setup of the POISE study. In the first part of the study, in particular, the protocol allowed patients to be given a very high dose of metoprolol – up to 400 mg / day even though the investigators claim that no patient received this high dose [25]. Starting beta-blockade with doses in this range requires a high degree of surveillance. Bradycardia and hypotension may follow and there is some evidence that hypotension may be an even stronger indicator of postoperative myocardial infarction than hypertension [9, 26].

Furthermore, patients in the POISE study were not evaluated with echocardiography before the start of medication, which may imply that some of patients could have latent cardiac failure. Cardiac failure is a strong negative prognostic factor for patients undergoing non-cardiac surgery [3]. Beta-blockade is a cornerstone in the modern treatment of heart failure but needs to be titrated up slowly with a close attention to increasing symptoms. Therefore, it seems reasonable to have an echocardiographic evaluation of patients before starting preoperative beta-blockade to high risk patients before major non-cardiac surgery.

Some have advocated titration of beta-blockade to a heart rate between 60 and 70. Bickard and co-workers [26] in a meta-analysis did not find any connection between reduction in heart rate and positive effects of beta-blockade. A recent study from the Poldermans’ group demonstrated increasing protection by beta-blockers when started more than one week before non-cardiac surgery [27]. Iliuta and co-workers [28], in a multicentre study from Romania involving more than 1300 patients, found better prevention against postoperative atrial fibrillation with betaxolol than with metoprolol in cardiac surgery.

If confirmed, it will indicate that not only the drug family (e.g. beta-blocker) but also the specific drug molecule (e.g. β-xolol or bisoprolol) may be of importance.

Arguments against the efficiency of metoprolol have been forwarded by others [29]. Scott Beattie and colleagues [30], in a cohort study of 1153 Scottish patients undergoing non-cardiac surgery and were given beta-blockers within 24 h of surgery, showed that the beta-blocked patients with low haemoglobin values during the first 3 days of after surgery had worse outcomes than those without. Since beta-blockers mitigate the physiological response to hypovolaemia and anaemia, this seems logical and underlines the complex nature of optimization of perioperative management stressing that there is no magic bullet that solves the problems – the skilled perioperative physician is irreplaceable (Table 4).

Statins

Prospective and retrospective studies have indicated that statins improve results in cardiac patients with non-cardiac surgery [31, 32]. It is therefore recommended that statins are started in high-risk patients before surgery and continued perioperatively including the day of surgery [11].

Other drugs

Drugs like angiotensin-II blockers and ACE-inhibitors lead to hypotension and may reduce the renal blood flow. Case studies have described severe vasodilatation and perioperative hypotension that has been difficult to manage [33, 34]. Based on our experience we have stopped these drugs the day before surgery for indications being both hypertension and cardiac failure. Calcium antagonists can also induce hypotension but to a lesser degree. The documentation for stopping or continuing is scarce yet it is not uncommon to give them at the morning of surgery.

HEART FAILURE

Heart failure has received much attention in recent years with regard to prevention, diagnosis and treatment. Cardiac failure may be overt with classical symptoms, as dyspnoea and fatigue, or latent where diagnosis can only be made through more than one indicator. It is associated with high levels of N-terminal B-type natriuretic peptide (pro-brain natriuretic peptide (NT-BNP) and B-type natriuretic peptide (brain natriuretic peptide (BNP). High levels of these indicators are associated with increased risk of death with non-cardiac surgery [35, 36, 37]. Hammill and co-workers [3] analysed data from 159 327 patients above the age of 65 in a cohort of patients undergoing non-cardiac interventions in the period 2000-2004. Patients who were diagnosed with heart failure within the 20 months preceding surgery had significantly higher 30-day mortality (8%) compared to 3.1% of patients with coronary artery disease and 2.4% in a control group without such diagnoses [2, 3]. A large cohort study like this is excellent for putting forward hypotheses but cannot document that preoperative treatment of cardiac failure improves outcome in non-cardiac surgery. On the other hand, the data provides strong arguments for optimization of cardiac failure and delay of elective non-cardiac surgery until the indicators of cardiac failure decrease.

INTRAOPERATIVE MANAGEMENT

Haemodynamic control

Though there are scarce data concerning the specific requirements of cardiac patients in non-cardiac surgery, it is reasonable to assume that there are more narrow margins for haemodynamic variations and that stable haemodynamics will improve outcome. Thus, the following will refer to data coming from different studies of non-cardiac surgery. Tachycardia, especially when accompanied by hypotension, can lead to coronary events and cerebral hypoperfusion. The potential consequences are myocardial infarction and stroke. Anaesthesiologists are constantly in search of better methods for treating difficult patients and stable haemodynamics is a primary goal, which is likely to be achieved through the skills of anaesthesiologists rather than choosing one particular method of anaesthesia [5, 38, 39]. Good planning by relating the speed and dosage of drugs to a specific patient and to stressful moments as intubation and start of surgery will pave the way for uneventful anaesthesia. The modern anaesthesiologist with kn
owledge of physiology and the physiological actions of drugs has adequate tools for controlling the haemodynamic situation. We can provide adequate fluids to ensure optimal cardiac filling (Starling’s mechanism), drugs like beta-blockers, noradrenalin and dobutamine can help controlling cardiac performance and peripheral vascular resistance. Despite the importance of fluid loading, the fall in blood pressure is primarily caused by vasodilation. An example is the use of remifentanil, which can cause severe hypotension in combination with propofol. When starting low dose noradrenalin (e.g. 0.05 µg kg-1 min-1) along with the infusion of remifentanil and before induction with propofol, the blood pressure is kept stable. Most of our induction agents cause vasodilation. A relatively pure alpha-agonist like phenylefrine is helpful in low bolus doses. Diluted to 0.1 mg mL-1 it provides an excellent tool for rapid correction in blood pressure in doses of 0.5-1 mL. Moreover, ephedrine in low intravenous bolus (2.5-5.0 mg) or subcutaneously (25 mg) is useful, especially in prevention of hypotension in regional anaesthesia, despite the fact that even these low doses may sometimes result in hypertension and tachycardia.

Goal-directed haemodynamic monitoring and therapy

The concept of goal-directed management is aimed to ensure sufficient tissue perfusion and is based on the notion that this can be obtained by navigating towards preset haemodynamic goals – either being defined by arterial blood pressure, cardiac stroke volume, intra-cardiac pressures or the level of central venous oxygen saturation (SvO2). Traditionally, this management has strived to obtain supra-normal values for oxygen transport (>550-600 mL min-1 m-2), cardiac output (3.5-4.5 L min-1 m-2), blood pressure (mean >70 mm Hg), pulmonary artery wedge pressure (~ 18 mm Hg) or SvO2 (>70%) [40]. This type of management required extended haemodynamic monitoring which helped in understanding the physiology during surgery without giving definite outcome advantages.   

In cardiac patients, rapid corrections of haemodynamic changes are necessary. Continuous ECG (with ST-indicator), pulse oximetry, measurement of hourly diuresis should be standard practice. In our experience the use of intra-arterial blood pressure measurements is very useful in providing very early signals of haemodynamic deterioration and thus, enabling a rapid correction. We would also recommend central venous cannulation least not because it gives a rapid access to the circulation when haemodynamically active drugs or fluids are needed. In cardiac patients having major surgery (vascular, major abdominal), it is reasonable to increase the level of monitoring to ensure stable oxygen supply to vital organs. We recommend to use a system for measuring cardiac output and mixed venous oxygen saturation, if available. Perioperative echocardiography has become the standard in cardiac surgery. The machines are becoming more reasonably priced but their use requires a skilled operator. In very few institutions are th
e cardiologists able to cope with the demands in operating rooms. Thus, the coming years will challenge the anaesthesiology community to provide education to the junior staff in echocardiography, which then will become a natural part of intraoperative management of cardiac patients in non-cardiac surgery.

Despite the insight we have gained into different types of monitoring, they have not been shown to improve outcomes [40, 41]. In our opinion, this is not a valid argument for avoiding their use. The present insight into perioperative physiology depends on the knowledge of physiological processes that we can only gather by the parallel use of clinical signs and extended monitoring, which is a part of the ongoing search for better understanding and striving for improved management strategies.

FLUID MANAGEMENT

Goal-directed therapy can lead to fluid overload if the anaesthesiologist is guided only by haemodynamic indices. When a liberal fluid programme is followed, it may lead to bowel oedema during abdominal surgery and be one of the reasons behind the increased frequency of complications [42]. According to some studies, a more restrictive fluid policy has showed reduced morbidity in colorectal surgery; others found that a too restrictive regimen increased the complication rate [42, 43, 44, 45]. The old discussion on the use of crystalloids or colloids in perioperative management has been continued and several authors warn against the liberal use of crystalloids in non-cardiac surgery. “Old wisdom” is becoming en vogue urging the practitioner to separate the need for blood products, like plasma and albumin, from the need for interstitial fluids (crystalloids) when the patient is bleeding [46].

Despite the importance of evidence, no study is able to give all the answers when treating the patient. A thorough understanding of the advantages and shortcomings of monitoring techniques and fluid regimens is necessary to balance treatment. We therefore emphasize the relevance of training and skills showing that a well-trained and alert craftsman cannot be substituted by standardized fluid algorithms or advanced monitoring [38, 39].

ANAESTHETIC DRUGS

Anaesthetic drugs cause vasodilation and inhalational agents are important for avoiding intraoperative hypertension. Recent literature has indicated that inhalational anaesthetics are superior to others in providing a specific myocardial protection. These data come mainly from experimental studies, studies with limited power and mostly from patients undergoing cardiac surgery [47]. Cardiac surgery has specific characteristics making it difficult to generalize to non-cardiac surgery. Thus, there are no available solid data to support one anaesthetic drug compared to another in non-cardiac surgery.

REGIONAL OR GENERAL ANAESTHESIA?

As previously stressed, few studies of intraoperative management are confined to cardiac patients leaving us to take the essence of studies of a general patient population. Spinal and epidural techniques cause vasodilation. When the blockade reaches the dermatome Th4, increasing inhibition of the sympathetic drive to the heart will occur. This leads to reduced heart rate and myocardial contractility mostly in the same way as with beta-blockade. The beta-receptors will remain intact and susceptible to stimulation by sympathomimetics like ephedrine and dobutamine. The combination of general and regional anaesthesia is the path between Scylla and Charybdis. It has the potential to stabilize the haemodynamics during surgery but may also lead to unexpected and profound blood pressure dips. It requires the anaesthesiologist to have a profound understanding of the method and to be alert and counteract bradycardia and hypotension [7, 25]. With an effective epidural block, the patient will be awake without pain.

Sprung and co-workers identified general anaesthesia as a risk factor in vascular surgery [1]. The meta-analysis coming from Rodgers and co-workers [48] demonstrated significantly lower perioperative mortality with regional anaesthesia compared to general anaesthesia. The regional blockade was associated with lower incidence of pulmonary emboli, stroke and cardiac events. Despite the acclaim from regional analgesia proponents, there are serious objections to the analysis and conclusion. It contains many older studies where the patients did not receive the modern form of thrombotic prophylaxis, the fact which severely weakens its impact. In a major prospective multicenter study from Australia, more than 900 high-risk patients were randomized to general or intra- and postoperative epidural anaesthesia/analgesia [49]. Lower incidence of pulmonary complications was found with regional blocks but the mortality rate was the same. Norris and colleagues [50] in their randomized study of aortic surgery patients did not demonstrate differences in mortality or cardiac problems.

Wu and co-workers [51] performed a cohort study of 12817 patients undergoing colectomy where one group (n=2 253) was registered to have postoperative epidural analgesia whereas the other group (n=10 564) had not. The epidural group had lower mortality both 7 and 30 days after surgery. In a cohort study, the selection bias cannot be excluded. The most dedicated anaesthesiologists and surgeons might have chosen to use regional anaesthesia to enable better perioperative care. There were no differences in postoperative organ complications, which could explain the reduced mortality in the regional anaesthesia group. The same authors calculated that in order to show that regional anaesthesia lowered mortality in high-risk surgery (e.g. vascular surgery), 24 000 patients should be enrolled while 1.2 million patients were needed in low-risk surgery (e.g. hip surgery). In practical terms, it means that the most important factor when deciding to use regional anaesthesia is the ability to maintain stable circulation and optimal postoperative pain relief.

In carotid surgery the blood flow must be stopped through the operated vessel. With regional anaesthesia the patient can be awake and report any neurological symptoms. A prospective multicenter study did not find improved neurological outcome or cardiac complications when regional anaesthesia was used [52].

Cardiac patients are often treated with aspirin, low-molecular-weight heparin and platelet inhibitors which increase the risk of bleeding in neuraxial block. The removal of an epidural catheter involves a hazard for bleeding as much as insertion, meaning that surveillance of the patient after removal of the catheter should be institutionalized. The European Society of Anaesthesiology has recently published the guidelines on this topic [53].

LAPAROSCOPIC SURGERY

When the abdominal pressure increases due to gas insufflation for laparoscopy, it may cause a fall in cardiac preload and reduction in stroke volume. Patients with hypertension or aortic stenosis who have reduced ventricular compliance will be particularly susceptible. In a small patient study, the physiological changes were reduced by strapping the legs during surgery and thus maintaining the stroke volume [54]. Retrospective studies have indicated that cardiac patients subjected to laparoscopy do no worse than others [6, 55]. The picture is complicated since patients with heart failure did worse than patients with coronary artery disease and controls, both in open as well as in laparoscopic procedures [3]. Thus, in a specialist setting with proper monitoring there is no need to avoid laparoscopic techniques, which may ease the postoperative course.

POSTOPERATIVE PAIN RELIEF AND AMBULATION

Pain and anxiety increase the sympathetic tone promoting ischaemia and prolonging the time to recovery. There is little documentation that adequate pain relief reduces organ complications or improves outcome but ethical considerations preclude randomized studies. The choice of postoperative pain relief in cardiac patients must therefore be based on general expectations of postoperative pain, the need for early ambulation and resources for follow-up in wards.

ORAL AND INTRAVENOUS PAIN RELIEF

Despite extensive research in postoperative algology, pain relief after major non-cardiac surgery is still a challenge [56, 57, 58, 59, 60, 61, 62]. Regional analgesia is the most effective and most centres will have written instructions to nurses on how to administer opioids immediately after surgery. Light analgesics and slow-release, long acting drugs may be advantageous on the ward. Patient-controlled analgesia employs a system of pumps that may enable the patient to self-administer the drugs within predefined limits for the individual bolus and time, a system providing greater patient satisfaction [60]. 

NON-STEROID ANTI-INFLAMMATORY DRUGS (NSAIDS)

Despite the efficacy there is concern of their use in cardiac patients for postoperative pain management; COX-2 inhibitors, in particular, have been subjected to scrutiny due to reports of cardiac and renal failure. Compared to the ordinary NSAIDs, these drugs reduce the potential for gastrointestinal bleeding, perioperative bleeding, bronchospasm or delayed healing. It seems that the risk of renal failure is low for both families of drugs if they are avoided in patients with renal failure and those with impaired tissue perfusion [63, 64, 65]. The risk of developing heart failure appears to be similar for the two types. There are arguments for avoiding both types when a patient has renal failure, heart failure or serious angina pectoris. A patient on diuretics should give rise to caution. Postoperative ambulation improves well-being but there are no good studies to show that cardiac patients in non-cardiac surgery have improved outcome when subjected to fast track surgery. Extrapolation from physiology and ot
her patient groups encourages a regimen of early postoperative ambulation [66, 67, 68].

NUTRITIONAL STATE, TEMPERATURE, PHYSIOTHERAPY

Perioperative nutrition

Impaired preoperative nutrition in patients with critical illnesses is associated with reduced resistance to infection. The patients have weaker muscles for ventilation and therefore lower ability to breathe deeply, thus longer ventilation is required. Some studies indicate that optimization of nutrition may improve the total outcome after surgery but larger randomized studies are lacking [68, 69].

Perioperative hypothermia, hyper-oxygenation and postoperative ventilatory support

Hypothermia may increase the incidence of bleeding and wound infection. Postoperative shivering increases oxygen demand, which is harmful for patients with marginal oxygen transport. Thus, it seems reasonable to ensure normothermia postoperatively [70]. There is conflicting evidence whether inhalation of high concentrations of oxygen is advantageous in the perioperative setting [71, 72, 73, 74, 75]. The prophylactic use of physiotherapy, continuous positive end-expiratory pressure or non-invasive positive pressure ventilation has not been shown to improve postoperative lung function. All these methods are effective in the management of pulmonary failure after surgery [76, 77].

In conclusion, there is a large number of studies addressing the perioperative management. Only few have sufficient power to provide a solid basis for management guidelines. Large European multicenter studies are planned by the European Society of Anaesthesiology and will hopefully complement the picture. Education and training of anaesthesiologists are vital to integrate the current knowledge for safe management.

Therefore, so far, the main messages are as follows:

• few studies have strict methodological strengths and statistical power to support a specific way of perioperative management of cardiac patients coming for non-cardiac surgery,

• in patients with serious cardiac disease the full surgical team including a surgeon, anaesthesiologist, cardiologist or other specialists like haematologists must convene to produce an optimal perioperative plan,

• perioperative beta-blockade may be advantageous in high-risk patients or in cardiac patients for high-risk surgery. The treatment should start preferably one month before surgery and should be closely monitored. Perioperative bradycardia and hypotension should be treated vigorously to avoid complications,

• regional anaesthesia/analgesia alone or in combination with general anaesthesia have not been shown to reduce mortality but may be important for an active postoperative mobilization regimen.

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..............................................................................................................................................................

address:

*Professor dr med Olav F. Münter Sellevold
e-mail: olav.sellevold@ntnu.no
AHL Centre, St Olavs Hospital
Prinsesse Kristinas gt 3,
NO 7030 Trondheim, Norway
tel.: +47 72 82 68 23
mobil: +47 926 12 568

received: 28.01.2011
accepted: 16.04.2011