The post-operative mortality rate of elderly patients is high  and the assessment of the risk of perioperative complications very difficult. In respect of the post-operative outcome, age per se may not be as important as the patient's overall physiological status [2,3].
Peri-operative myocardial infarction (MI) is the major cause of post-operative death in the elderly undergoing noncardiac surgery . The prevalence of ischaemic heart disease (IHD) increases with age , and the ability of the heart to respond to physical stress is also reduced [6,7]. Diabetes mellitus (DM) is another risk factor for myocardial ischaemia [8,9] and post-operative mortality . In diabetic patients  myocardial ischaemia may be silent, without any pain , and may therefore not be recognized. In general, post-operative ischaemia seems to be most severe during the early recovery period .
The anaesthetic technique has a minor impact on cardiac outcome. Several studies have shown an equal incidence of cardiac morbidity and mortality after general and regional anaesthesia [12-14]. Major orthopaedic and peripheral vascular surgery are both associated with an increased risk of post-operative cardiac events . Further, mild peri-operative hypothermia has been shown to be related to post-operative myocardial ischaemia [16,17] and an increase in plasma norepinephrine (NE) concentrations [18,19].
The aim of this primary study was to evaluate the above-mentioned factors associated with post-operative myocardial ischaemia in elderly patients undergoing elective hip arthroplasty or peripheral vascular surgery.
Forty patients over 65 years of age undergoing elective hip arthroplasty or peripheral vascular surgery were included in the study. The study protocol was approved by the ethics committee of the hospital. All patients gave informed consent. The exclusion criteria were base-line electrocardiographic (ECG) changes suggesting cardiac ischaemia (left bundle branch block, left ventricular hypertrophy with strain, or ST-T wave changes associated with digoxin) or the patient's refusal to carry an ambulatory ECG (Holter) monitor peri-operatively. The patients took their regular cardiovascular medication during the study. Patients taking β-blockers or nitrates were given these drugs before surgery. Patients taking any ACE-inhibitor were given captopril. All patients were premedicated with oral diazepam 0.15 mg kg−1.
Monitoring and anaesthesia
A radial artery and the right internal jugular vein were cannulated before the induction of anaesthesia for measurement of mean arterial pressure (MAP) and central venous pressure (CVP). In all patients intravascular volume loading was performed with Ringer's acetated solution 8 mL kg−1 before the induction of anaesthesia and 2 mL kg−1 h−1 thereafter. Blood loss was replaced with 6% hydroxyethylstarch (Plasma-fucin®, Pharmacia & Upjohn, Norway) up to 20 mL kg−1 and packed red cells. MAP was not allowed to deviate more than 30% from the pre-operative level. CVP was kept above 4 mmHg using additional volume loading with Ringer's acetated solution if required. The patients who needed dopamine to maintain arterial pressure during surgery were excluded from the study. A Foley urinary catheter was inserted in all patients. Urine output was kept ≥ 1 mL kg−1 h−1. If necessary, 15% mannitol 100 mL was given. Base-line arterial blood gas analysis was performed without oxygen supplementation. Warm blankets and a warm waterbath mattress (39°C) were used to maintain the body temperature during surgery.
On arrival in the operating room the patients were randomly assigned, using an envelope-method, to receive either spinal or general anaesthesia for surgery. In five patients scheduled for hip arthroplastic surgery spinal anaesthesia was induced with 0.5% plain bupivacaine 4 mL (=20 mg) injected through the L3-4 interspace. In 15 patients undergoing peripheral vascular surgery a spinal catheter was inserted through the same interspace and a similar dose of plain bupivacaine (20 mg) given. The level of spinal block was evaluated with the loss of a sharp sensation to pinprick. Later during vascular surgery, an additional bolus of 0.5% bupivacaine 1 mL (=5 mg) was given through the spinal catheter, if necessary. No bupivacaine was given post-operatively. The remaining five arthroplastic and 15 vascular surgical operations were performed under general anaesthesia. General anaesthesia was induced with thiopentone and fentanyl, and maintained with isoflurane in 65% nitrous oxide and 35% oxygen. Vecuronium was used for muscle relaxation. No anticholinergics were given.
Heart rate (HR), MAP and CVP were measured (Cardiocap®, Datex, Finland) before and 30 min after the induction of anaesthesia and 60, 90, and 120 min after the incision. Pulse oximetric haemoglobin saturation (SpO2) was monitored continuously. Post-operatively, the haemodynamic parameters were measured on arrival in the recovery room and every 30 min until the patient was discharged from the recovery room. Sublingual temperature and urine output were also recorded on arrival and at discharge. Degree of sedation, pain and nausea were recorded at arrival and hourly after the arrival in the recovery room. Oxycodone (0.07 mg kg−1 i.v. or 0.15 mg kg−1 i.m.), a morphine-like opioid, was used for post-operative pain treatment.
Detection of cardiac complications
Holter recordings were obtained continuously from the pre-operative evening until the third post-operative morning using a two-channel AM Holter ECG recorder (Marquette 8500®, Milwaukee, WI, USA). Two bipolar electrodes on the inferior and lateral leads were used. The Holter recordings were analysed when the patient had completed the study using a Marquette 8000® computer-based scanner. A QRS complex and dysrhythmia classification provided by the scanner was checked and edited by the operator. After exclusion of all abnormal QRS complexes, an ST segment was trended continuously for the two leads. All recordings were analysed by a 'blinded' technician and verified by two of the authors. The base-line level of the ST segment was defined as the average ST segment during a stable period preceding each ischaemic episode. An ischaemic episode was defined using two criteria: (a) The ST segment depression was measured 60 ms after the J-point. A horizontal or down-sloping ST segment depression of ≥ 1 mm below the baseline lasting ≥ 1 min, or (b) elevation of the ST segment (≥ 2 mm) at the J-point. The number of ischaemic episodes, total duration of ischaemia, and ischaemic minutes per hour were recorded for each patient perioperatively.
In all patients, a standard 12-lead ECG was taken before surgery and on the three consecutive post-operative days. The concentrations of serum creatine kinase including MB fractions and troponine T were measured the evening after surgery and on the three post-operative days. Subsequently, an additional ECG was taken and the concentration of creatine kinase and troponine T analysed when necessary.
A diagnosis of myocardial infarction was made if two of the three criteria were fulfilled: (a) New Q-waves in the ECG, (b) ST-segment depression ≥ 1 mm from the pre-operative base-line on at least one lead, and a creatine kinase concentration ≥ 300 U L−1 with the MB fraction ≥ 5% or (c) positive troponine T (> 0.2 μg L−1).
Analysis of plasma catecholamines and lactate
Blood samples for measurement of plasma concentrations of epinephrine, norepinephrine and lactate were drawn from the central venous catheter before the induction of anaesthesia, during surgery before the application of the cement in hip arthroplasty or before the opening of the arterial circulation to the leg in peripheral vascular surgery, 1 h after arrival in the recovery room, and on the first post-operative morning. Blood samples were drawn from the superior vena cava because plasma catecholamines, especially norepinephrine, are selectively taken up by the lungs . The plasma concentrations of the catecholamines were measured using high-performance liquid chromatography (HPLC) with electrochemical detection . The intra-assay coefficients of variation were 2% for norepinephrine and 10% for epinephrine at physiological concentrations. The plasma concentration of lactate was measured using an enzymatic spectrophotometric method in the clinical laboratory of the hospital.
Chi-square analysis with continuity correction was applied to the categoric data. The data between the patients with and without myocardial ischaemia were compared using unpaired t-test and Mann-Whitney U-test. The Holter recordings were divided according to the three periods: the pre-operative period with the hours before surgery, the intra-operative period during surgery and in the recovery room, and the post-operative period from the discharge from recovery room until the third post-operative day. A regression line was drawn between the increase in plasma norepinephrine concentrations and the decrease in core temperature in patients with or without post-operative ischaemia. The calculations were performed using StatView 512 + TM® software (Brain Power Inc., Calabasas, CA). A P-value ≤ 0.05 was considered statistically significant.
The demographic details of the patients undergoing hip arthroplasty and peripheral vascular surgery have been shown in Table 1. The history of IHD or DM was similar in patients with either type of surgery. Before surgery the patients were monitored for 16 h (range 10-21 h), on average, intra-operatively for 8 h (range 6-13 h) and post-operatively for 64 h (range 59-68 h). There were altogether 251 ischaemic episodes with a duration of 6482 min (108 h 2 min), a mean duration of 15 min per episode, and a mean of 381 min (6 h 21 min) per patient with ischaemia.
Seventeen (43%) of the 40 patients had at least one period of myocardial ischaemia in the Holter recordings. The incidence of myocardial ischaemia was similar in both surgical groups. Eight patients had β-blocker in their pre-operative medication and three of them developed post-operative myocardial ischaemia. Eight patients had ACE-inhibitors in their pre-operative medication and three of these developed post-operative myocardial ischaemia. Five patients had diuretics in their pre-operative medication and one of these developed post-operative myocardial ischaemia. Diuretics, however, were not given preoperatively. The patients with pre-operative cardiovascular medication (β-blocker or ACE-inhibitor or diuretics) did not have peri- or post-operative myocardial ischaemia more often than those without pre-operative cardiovascular medication. The type of anaesthesia had no effect on the incidence of myocardial ischaemia during or after surgery.
The mean HR during the study period was similar in patients with and without peri-operative myocardial ischaemia.
Males had more frequent pre-, intra- or post-operative myocardial ischaemia than females. The patients with peri-operative ischaemia more frequently had a history of IHD and DM than those without ischaemia. Patients with peri-operative ischaemia received more colloid solution during surgery but intra-operative CVP recordings were similar in patients with and without ischaemia (Table 2).
Post-operative myocardial ischaemia was observed in 16 patients (40%) in the Holter recordings. It was associated with a positive history of IHD (P < 0.05) and peri-operative ischaemia (P < 0.05). CVP and MAP were lower during the early recovery period in patients with ischaemia than in those without (P < 0.05) (Table 3).
Plasma catecholamines, lactate, and post-operative ischaemia
The plasma concentration of NE was significantly increased during surgery in patients developing post-operative ischaemia (P < 0.05). On the first post-operative day the plasma concentration of NE increased further in these patients, but the change was not significant (Fig. 1). The decrease in core temperature during surgery correlated with the intra-operative increase in NE in patients with post-operative myocardial ischaemia (r=0.64, P < 0.05), but not in those without ischaemia (r=0.08, NS). Post-operatively plasma concentrations of epinephrine increased similarly in patients with and in those without post-operative ischaemia. The plasma concentrations of lactate were similar in patients with and without post-operative ischaemia.
Adverse cardiac outcomes
An episode of atrial fibrillation was seen in one patient post-operatively. Four (10%) post-operative myocardial infarctions were detected during the study period. There was no statistically significant relation between the incidence of peri-operative ischaemia in patients who later did and those who did not develop a post-operative myocardial infarction. However, on the first post-operative day myocardial ischaemia tended to be more common in patients with than in those without a subsequent post-operative infarction (NS) (Table 4).
The aim of this primary study in a small group of patients with high risk of IHD was to detect if there is any intra-operative parameter which would be associated with post-operative myocardial ischaemia. We found that in patients who later had post-operative ischaemia, an intra-operative increase in the plasma concentration of NE correlated with a peri-operative decrease in core temperature. As expected, the type of anaesthesia or surgery had no effect on the incidence of myocardial ischaemia.
Ischaemic heart disease is not uncommon among patients undergoing elective peripheral vascular surgery (21-54%) [9,14,22-24] or hip arthroplasty (31%) . All our patients had either a history of IHD or one or several of the risk factors of IHD documented by Mangano and co-workers. . These include vascular surgery, age > 65 years, and DM. In our study intra-operative myocardial ischaemia was seen in 25% and post-operative myocardial ischaemia was seen in 40% of the patients. This is in accordance with earlier studies [8,26] in patients with definite IHD or at high risk of it. A history of IHD associated with post-operative ischaemia and cardiac events has also been reported previously [9,13].
The catecholamine response to surgery is reduced in elderly patients . However, an increase in the plasma concentration of NE was found during surgery in those of our patients who later developed post-operative ischaemia. Further, in these patients the increase in NE correlated with a decrease in core temperature. Frank and co-workers have demonstrated an association between mild peri-operative hypothermia and post-operative myocardial ischaemia [16,17] and subsequently an association between a decrease in core temperature and an increase in NE concentrations [18,19]. Thus, the intra-operative increase in the plasma concentration of NE in our elderly patients developing post-operative myocardial ischaemia was most probably caused by decreased core temperature.
Increased circulating levels of catecholamines have been reported in patients with acute myocardial ischaemia thus reflecting systemic sympathetic activation [28-30]. Systemic plasma catecholamine concentrations, however, are poor indicators of local catecholamine concentrations within the ischaemic myocardium, since the contribution of the heart to the circulating catecholamine levels is less than 3% . Thus the local NE concentrations in the coronary sinus might have been significantly higher than the systemic concentrations of NE. Significantly increased systemic NE concentrations have also been measured in patients with congestive heart failure [32,33] and with complete atrioventricular block . Thus, another explanation for the increased NE concentrations in patients with post-operative myocardial ischaemia may be latent cardiac dysfunction caused by hypothermia-related peripheral vasoconstriction .
In our study the post-operative myocardial infarction rate was 10%. In earlier studies the incidence of perioperative myocardial infarction has been 2-15% in patients undergoing elective hip arthroplasty  or peripheral vascular surgery [9,23,24,35]. Post-operative myocardial ischaemia has a strong association with post-operative cardiac morbidity [11,22,26,36]. In our study the incidence of peri-operative ischaemia did not increase the probability of a later post-operative myocardial infarction. The report by Fleisher and co-workers speculated that myocardial ischaemia and infarction may be two separate events that are both related to underlying IHD . However, because of the small sample size our study neither confirms nor rejects the association between post-operative ischaemia and cardiac morbidity.
In conclusion, an intra-operative decrease in core temperature may cause latent cardiac dysfunction leading further to post-operative myocardial ischaemia. Measurement of the intra-operative plasma concentration of NE in high-risk patients may help identify those with an elevated risk of post-operative myocardial ischaemia.
The authors are indebted to the anaesthetic staff of the Fourth Department of Surgery, HUCH for their skilful assistance during this study. We are also grateful to Ms Helena Kovapohja for the analysis of the Holter recordings.
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