Annals of the Royal College of Surgeons of England (1976) vol 58
Medical problems of surgical patients Hypertension and ischaemic heart disease C Prys-Roberts DM FFARCS Nuffield Department of Anaesthetics, University of Oxford
Summary Pre-existing disease in the form of hypertension or ischaemic heart disease may increase morbidity and mortality in patients presenting for anaesthesia and surgery. The interaction of these two cardiovascular conditions in relation to anaesthesia has been studied in a series of II5 patients. The results did not support the view that antihypertensive drugs and /3receptor blocking agents should be withdrawn before anaesthesia and surgery. The main cause for concern in providing anaesthesia for these patients is that sympathetic nervous activation induced either by anaesthetic manoeuvres or by surgical stimulation may lead to reflex cardiovascular responses which, by increasing myocardial oxygen demand, lead to episodes of myocardial ischaemia. In this respect P-receptor blocking drugs appear to have a protective effect on the ischaemic myocardium.
Introduction Hypertension and ischaemic heart disease, afflictions which increase the risk of anaesthesia and surgery for patients who suffer from them, are phenomena of the 20th century. They were unkown at the time of William and John Hunter-indeed, little was then known about arterial pressure. At or about the time that John Hunter was born the Reverend Stephen Hales, curioius about the facts of nature and motivated to define 'the forces and velocity with which fluids are impelled', after determining with remarkable accuracy the force required to drive sap to the top of a tall tree', turned his attention to measuring the blood pressure of a conscious mare2. Hales also introdtuced the concept of peripheral resistance in the vascular system and, in experiments on intestinal blood vessels, showed that the main site of this resistance lay in the minute vessels Hunterian Lecture delivered on 7th April T976
of the gut wall. He strengthened the concept by showing that various agents, including brandy, could change the rate of flow of blood through these vessels. Hales's experimental work did not apparently influence any followers, and the rest of the i 8th and igth centuries were notable, at least in the field of fluid dynamics, for the great theoretical developments of Euler, Bernoulli, Navier, and Stokes. It was left to the Frenchmen Jean Louis Poiseuille and Etienne Jules Marey to measure blood flow and pressure in animals and to start the experimental validation of the theorists. Poiseuille introduced the UT-tube mercury manometer and, with Ludwig's float and pointer recording on a kymograph, started the process of arterial pressure measurement. The studies of Richard Bright3 into the aetiology of renal disease and the observations of Gull and Sutton4 relating Bright's disease to hyalin-fibroid formation in the walls of small arteries were related to the blood pressure measured in life only at a later date. Mahomed5, using crude methods for measuring blood pressure, showed that renal failure was only one outcome of Bright's disease and that death occurred more commonly from heart failure or cerebral haemorrhage secondary to high blood pressure. Thus began the period when the idea developed that high arterial pressure could exist independently of Bright's disease. Sustained high arterial pressure was known by a variety of names such as 'latent arteriosclerosis' (von Basch), 'hypertension permanente' (Huchard), and 'hyperpiesis' (Allbutt). The term coined by Frank was 'essentielle Hypertonie', a term which has remained with us as 'essential hypertension' even if the meaning is somewhat different. Frank used the term to imply that the high arterial pressure was 'essential' to overcome a
466
C Prys-Roberts
high peripheral resistance, whereas we now regard high arterial pressure as the result of flow into a high resistance. Finally, the monumental work of Volhard and Fahr' classified the various pathological causes of high arterial pressure, identifying renal and non-renal causes.
Until the 1920s pre-existing cardiac disease widely regarded as an absolute contraindication to surgery. In 1929 Sprague' found that the mortality in patients with cardiac disease subjected to surgery was highest in those with hypertension; 24 out of 75 died during or shortly after surgery, the majority succumbing to heart failure. It should be emphasized that Sprague's classification did not feature angina pectoris since it was considered even then an absolute contraindication to surgery. Seven years later Hickman, Livingstone, and Davies' described an operative mortality of I I/ in patients with hypertension but considered them a much better risk than those with angina pectoris, in whom the mortaity was 33%/0. This period saw the advent of the surgical treatment of hypertension and a dramatic improvement in mortality. While some centres, notably the Mayo Clinic, had an operative mortality of about 3 % in all patients, other centres recognized that a io% mortality was inevitable when a combined thoracolumbar sympathectomy was performed on patients with severe hypertension9, with a one-year survival of only was
54O/o. Drug therapy of hypertension started in Bose'" included hypertension amongst a number of conditions which were amenable to treatment with rauwolfia alkaloids, but it was not until the I950-60 period that drugs became popular in the management of hypertension. At this time little was known of the special risks involved in anaesthesia for the hypertensive patient and a controversy existed, which lasts to the present day, as to whether or not patients receiving antihypertensive drugs should have their therapy withdrawn for a period before anaesthesia and surgery. This controversy was international and interdisciplinary, since there anaesthetists, consensus among no was surgeons, or the physicians treating hyper193I, when Sen and
tensive patients as to either the nature and the extent of the risk involved in withdrawing antihypertensive therapy before surgery or the response of patients with high arterial pressure to anaesthesia. Widespread concern was expressed that antihypertensive drugs could disturb the maintenance of circulatory homoeostasis during surgery. Studies on the effects of anaesthesia in patients pretreated with rauwolfia alkaloids produced confficting results, and with the advent of more potent antihypertensive drugs there was scant information on the interactions of newer formns of therapy with the combined influence of anaesthesia and surgery. In their admirable reviews Dingle" and Hickler and Vandam" stresed the difficulties of reaching a rational conclusion to these issues, mainly owing to the paucity of information concerning the reactions to anaesthesia and surgery of treated and untreated hypertensive patients. Coronary artery disease and its consequences are the main complication associated with hypertension, pathological evidence of substantial coronary arterial lesions being found in more than 6o% of hypertensive patients at autopsy. Coronary artery disease is the major cause of death in hypertensive patients and is becoming predominant as other causes decline with successful antihypertensive therapy. Atherosclerosis affects the endothelial lining of major blood vessels, the primary lesion being the atheromatous plaque, which tends to narrow and occlude the arterial lumen, particularly at sites of vascular branching. There is abundant evidence in man and experimental animals that a sustained elevation of arterial pressure, regardless of its cause, aggravates and accelerates the development of the atherosclerotic process". The end result of coronary artery disease is myocardial infarction, a well-documented complication in the postoperative period'4. Most authors have identified pre-existing hypertension as a major factor in the development of intra- and postoperative myocardial ischaemia and of the subsequent myocardial infarction. Recurring themes in many of these discussions, particularly those in the American literature, have been the incidence, severity, and duration of intraoperative hypotension and the duration of surgery". Thus we are now familiar with
Medical problems of surgical patients
467
the coexistence of two disease states, hypertension and coronary artery disease, each of which may exist independently or aggravate the development of the other and both of which are common in older patients presenting for anaesthesia and surgery. When I commenced my studies of anaesthesia in relation to hypertension in I969 the questions seemed clear. Firstly, how did treated and untreated hypertensive patients respond to the induction and maintenance of anaesthesia, the surgical procedure, and the recovery from both? Secondly, was it possible to identify adverse cardiovascular responses to anaesthesia which could be related to preexisting antihypertensive therapy?
slow junctional rhythms (Fig. i) and was commoner in the presence of low arterial Pco2 induced by artificial ventilation. However, myocardial ischaemia also became evident in a number of hypertensive patients, both treated and untreated, if for any reason their arterial pressure rose dramatically during anaesthesia and surgery, commonly in response to: (i) laryngoscopy and endotracheal intubation'8; (2) bronchoscopy or tracheal suction; (3) surgical incision; (4) mesenteric traction; (5) aortic cross-clamping (aortoiliac surgery); or (6) recovery from anaesthesia. While it may be said that many of these reflex cardiovascular responses could be attenuated by deep anaesthesia, such a manoeuvre frequently induced sudden arterial Responses of hypertensive patients to hypotension as a result of junctional rhythm16 anaesthesia and surgery (Fig. 2). We began to recognize that preThe first pilot studies'6 indicated that patients disposition to myocardial ischaemia was a with untreated hypertension were less tolerant characteristic of many patients with untreated of anaesthesia than patients whose hyper- hypertension and of some treated hypertensive tension was well controlled and whose drug patients whose treatment was less than therapy was maintained up to and including adequate owing either to poor compliance with the day of surgery. Electrocardiographic drug taking on the patient's part or to evidence of myocardial ischaemia in the form inadequate medical attention. So the concept of flat ST-segment depression in the pre- developed that in this group of patients cordial leads was much commoner in un- impaired coronary arterial and myocardial treated hyertensives"6 17 and we were able perfusion could occur either because, during to relate this to periods of hypotension or hypotension, a normal myocardial oxygen hypertension during anaesthesia. When ST- demand exceeded a much reduced coronary segment depression, was associated with low blood flow or conversely because, during arterial pressure this was usually the result of hypertension and tachycardia, increased myo-
_ 1...4-
: .-:1-anaesthesia. (B) Responses to -..._ laryngoscopy and intubation-|--marked rise in arterial pressure and heart rate with onset of A-V
J.-
-1- -
A
B
AWAKE BEFORE ANAESTHESIA
DURING LARYIJGICOIf
-
1'-
-
C
D
FOLLOWING
MAINTENANE
INUBATIoN
HIG. I Adverse cardiovascular responses to anaesthesia in treated hypertensive patient. (A) Nornmal sinus rhythm with no evidence of myocardial ischaemia before
ANAEESIA
_-1:.
rhythm-contributing junctional to major increase in myocardial zvork resulting in mvocardial
ischaemia shown by flat, depressed ST segments in electrocardiogram. (C) Partial resolution of changes as arterial pressure and heart rate fall on completion of noxious stimulus. (D) Slow A-V junctional rhythm (isorhythmic dissociation) causing marked reduction of arterial pressure and further evidence of m10ocardial 1l.Chaen ia.
468
C Prys-Roberts
CMS
1:
| I--- '
ECf
.ji
1
load
~~: ARTERIAL PRESSURE
I
0S
mm Hg
PUILMONARY ARTERIAL
PRESSURE
Haemodynamic effects resulting from developof A-V junctional rhythm (isorhythmic dissociation) in patient with renovascular hypertension. Left-hand panel shows sinus rhythm (albeit with short P-R interval), high arterial pressure, and moderately elevated pulmonary capillary wedge pressure (balloon of Swan-Ganz catheter inflated at W) as indirect measure of left atrial pressure. Right-hand panel shows changes following onset of junctional rhythm causing 40% reduction of arterial pressure and rise of pulmonary capillary wedge FIG. 2 ment
pressure.
cardial
oxygen demand coronary blood flow.
exceeded the available
It also became apparent that those patients whose antihypertensive therapy had been maintained up to and including the period of surgery and whose arterial pressure was consequently closer to the normal range for their age showed fewer signs of physiological disturbances during induction and maintenance of anaesthesia. Furthermore, no adverse interactions have been observed between antihypertensive drugs and anaesthesic agents in any of the I I 5 patients who have been studied in depth so far, including 24 patients on high doses of 8-receptor blocking drugs"9. Our pilot studies led us to investigate in detail
these adverse cardiovascular anaesthesia and surgery, in particular the effects of different induction agents and their possible subsequent influence on the responses to laryngoscopy and endotracheal intubation. In comparisons of 7 induction agents or combinations in 48 patients the only more
responses
to
agents which appeared
unsatisfactory were diazepam and propanidid'8. However, all induction agents in doses which were considered appropriate for normal patients caused marked reductions of arterial pressure.
As a result of experience with patients with severe ischaemic heart disease undergoing coronary arterial bypass surgery I have modified my approach to induction olf anaesthesia in patients with hypertension. Fentanyl (3004oo0,g), which has little depressant effect on the cardiovascular system, is given intravenously followed by a small dose of thiopentone (25-50 mg) or I2 mg of Althesin (9 mg of alphaxalone + 3 mg of alphadolone acetate). In this way the depression of arterial pressure during induction can be minimized. Laryngoscopy and intubation of the trachea are stimuli which invoke reflex activation of the sympathetic nervous system to such a degree that significant hypertension and tachycardia occur even in normal, healthy patients. In patients with hypertension this response is exaggerated and very high arterial pressures may result"8 (Fig. 3). The combination of tachycardia and hypertension causes a major increase in myocardial work and therefore in myocardial oxygen demand. In patients with normal coronary vasculature this increased demand is easily satisfied and no adverse effects are apparent. In patients with coronary arterial disease, whether or not related to hypertension, such an increase in myocardial work may lead to acute impairment of oxygen supply to some areas of the myocardium supplied by diseased epicardial coronary arteries. This leads to dysrhythmia, ST-segment depression, and profound T-wave inversion, all signs of myocardial ischaemia (Figs. 3 and 4). A third factor in the genesis of myocardial ischaemia has become apparent more recently20. The subendocardial layer of the myocardium is the site in which collateral vessels develop in patients or animals whose epicardial vessels are atheromatous. These subendocardial collateral vessels, which supply adjacent endocardial and middle cardiac layers, are thinwalled and chronically dilated because of the low oxygen tension in this layer of the myocardial shell, which incidentally has the highest developed tension dturing contraction of any part of the myocardium. Consequently these collaterals may be easily compressed by high intracavitary pressure in the left ventricle, particularly during diastole, leading to impaired distribution of blood flow to the
Medical problems of surgical patients
469
20
RIGHT ATRIAL PRESSURE
mm Hg
't:
10
I; .. I.I 1, .~ o L±-4--[L-
250 200 1.
PRESSE nun Hg
100 1
0
L
L
I
_
i.
I-F -i
.1
I-
F7a--- L;~~ _1~~ 1 .L rTi F i I i, t'I -t - i-*, t-- t: t t - }-|
A -7 A
A: A-A-
-.t
-4-
t - 4
1
i.
1
1- --
lt
t
I.
i...
--l
~~~~~~~~~~~~~~~~~.;
FIG. 3 Haemodynamic responses of treated hypertensive patient to induction of anaesthesia followed by laryngoscopy and endotracheal intubation. At first arrow anaesthesia was induced with fentanyl (200 g,g) and thiopentone (ioo mg) and muscle relaxation obtained with pancuronium (6 mg). Anaesthesia was maintained with nitrous oxide (50%) and oxygen. At second arrow insertion of laryngoscope and endotracheal intubation caused marked hypertension, tachycardia and dysrhythmia associated with elevation of pulmonary capillary wedge pressure.
i
i- A-4t-4v t --1I ....I t
........ :
_..
20 r
PULKWMmI AMTESIAL WESUE
PRSSURE m g
15
-
10
-
5
i;
_. ..._. ... _. v....._ _.--'-t..
.^
OL 200
.. .. RATE
4 -
-l .... ........
-1- : j e
t * t~ ~ ~-~.i.!.tl.... -~ ~-i -
-t:'.-W :-:f:
|
:
0 *--
IT10 L
t- $ st~~~~~~~~~~~~~~~~
_t
p
~~~.-.
...t- .-i :---:.
....t.. 4i11
_----+iw............ ....... ......
-' '''~~~~~~~~~~~~~~~~~~.. A'6
....
-;t,-i---
-..i
--
...;;........... ...-.......
adjacent myocardium. That such high intracavitary pressures can occur during diastole has become apparent only with the advent of
drugs, increased sympathetic neurogenic activity at a-adrenergic nerve endings, or, in patients with renovascular hypertension, the Swan-Ganz balloon-tipped pulmonary circulating angiotensin formed as a result of artery catheter21, allowing indirect monitoring increased plasma renin levels22. of left atrial pressure (Fig. 2). High ventricular diastolic pressures indicate acute left Management of adverse effect ventricular failure in that the ventricle is Regardless of the causation of the increased incapable of developing sufficient force to myocardial work, the measures which we eject blood completely against a major might adopt to prevent this adverse effect in increase of systemic vascular resistance, the susceptible patients may be classified as latter resulting from arteriolar constriction. follows: Arteriolar constriction may be caused by (i) Suppression of noxious stimuli which Time.
sacs.
E.C.G. Lad U1 s Rae 60c per min. 40
Hurt
Orachial
IS.0.
Artery
Pressure 1t3 mm Hg..
oj Pulmonary
20
Artery Pressure mm
Hg.
ol Awake enesthesia
Befure
2 minutes after ntubetlon
mntnrachlu
10 minutes alter intubation 69*N20. 30%* 2 1% Halothane.
FIG. 4 Dysrhythmia and myocardial ischaemia developing as a result of hypertension and tachycardia in response to laryngoscopy and endotracheal intubation. The very high diastolic values of pulmonary arterial pressure during the period of bidirectional junctional tachycardia (centre panel) caused myocardial ischaemia, the ischaemic changes (depressed ST segment and inverted T waves: right-hand panel) persisting after resolution of the hypertension, tachycardia, and dysrhythmia. (Reprinted from the British Journal of Anaesthesia by permission of the publishers.)
470
C Prys-Roberts
may invoke reflex sympathetic activity by the use of local anaesthesia at the site of the noxious stimulus, deep levels of anaesthesia, or high doses of analgesic drugs.
(2) Suppression of the effector end-organs of the sympathetic nervous system, particularly those of the heart, by the use of 8-receptor blocking drugs.
(3) Limitation of the ability of the myocardium to increase its work and thus its oxygen demand, again by the use of P-receptor blocking drugs. (4) Reduction of left ventricular ejection load by vasodilator agents-for example, sodium nitroprusside, trimetaphan, hydrallazine-and a-adrenergic receptor blockers in certain appropriate conditions such as phaeochromocytoma. I would like to devote the remainder of this lecture to dealing with two of these measures to combat myocardial ischaemia; the use of [8receptor blocking drugs and the use of vasodilator drugs. Both are highly relevant to the management of hypertension and ischaemic heart disease since P-receptor blockers are rapidly becoming the predominant drugs in antihypertensive therapy and are already widely used in the management of angina pectoris and myocardial infarction. Many patients receiving large doses of P-receptor blockers are now presenting for anaesthesia and surgery, but despite growing experience with the pharmacology of these drugs there are many anaesthetists and surgeons who are reluctant to accept these patients for surgery.
have their propranolol therapy withdrawn at least two weeks before surgery24. Sudden withdrawal of 8-receptor blockers in patients with ischaemic heart disease may precipitate severe angina and even myocardial infarction25' 26; thus it is imperative that any withdrawal of these drugs should be gradual. However, recent studies of patients undergoing cardiopulmonary bypass27 28 have not confirmed earlier fears and have not documented any adverse reactions in patients on preexisting propranolol therapy. Our studies23 showed that in hypertensive patients deliberately pretreated with practolol* the hypertension and tachycardia associated with laryngoscopy and intubation were greatly attenuated and no dysrhythmia or de novo electrocardiographic evidence of myocardial ischaemia was seen in any of the 23 patients initially studied. This was in marked contrast to the incidence of dysrhythmia (4I %) and myocardial ischaemia (38%) observed in hypertensive patients who had not received 8receptor blockers18. There was no evidence that P-receptor blockers impaired cardiovascular performance in these patients; indeed, values of arterial pressure and cardiac output were slightly higher throughout anaesthesia than in hypertensive patients receiving what was then regarded as more conventional therapy. In a more recent study of patients with renovascular hypertension receiving doses of propranolol or other P-receptor blockers in doses between 240 and 2000 mg per day no serious adverse reactions were observed during anaesthesia and prolonged vascular surgery despite the severity of their disease state. I think it is now reasonable to conclude that for patients with hypertension or ischaemic heart disease maintenance of 8-receptor blocking therapy through the period of anaesthesia and surgery, far from causing adverse reactions, may be beneficial. Vasodilators While P-receptor blockade may be regarded as a prophylactic measure, the use of vasodilator drugs to reduce the impedance to left ventricular ejection must be regarded as a therapeutic measure in
Beta-receptor blockers My colleagues and I23 investigated the effects of 8-receptor blocking drugs in hypertensive patients for two reasons: firstly to find out whether these drugs would attenuate the sympathetic response to laryngoscopy and endotracheal intubation, and secondly to identify any adverse drug interactions occurring during anaesthesia. The second question has been particularly relevant in patients undergoing coronary arterial bypass *Practolol has now been withdrawn from general use surgery since it was proposed, largely on owing to the high incidence of side effects on the anecdotal evidence, that such patients should skin, eyes, and peritoneum.
Medical problems of surgical patients
patients with left ventricular failure. In the past left ventricular failure has been recognized by its traditional symptoms and signs. Nowadays, thanks to improved technology, we can define left ventricular failure in numerical terms and we can discriminate finer degrees of left ventricular failure than could be detected hitherto. In this respect the application of the Swan-Ganz balloon-tipped catheter29 for measuring pulmonary capillary w,Tedge pressure has enabled us to recognize the acute development of left ventricular failure and to apply the appropriate measures to treat it. The traditional concept defined left ventricular failure as an inability of the ventricle to maintain its output despite an elevated filling pressure, the implication being that, owing to a failure to generate sufficient force, the ventricle was unable to cope with venous return. A corollary of this view was that the treatment of left ventricular failure was based on the use of drugs such as cardiac glycosides, which exerted a positive inotropic effect, and diuretics, which reduced the peripheral or pulmonary oedema. Acute pump failure following cardiopulmonary bypass or in the acute phase of myocardial infarction was usually treated with adrenergic drugs having a positive inotropic effect. The disadvantage of this approach is that the treatment involves an increase in myocardial work, hardly acceptable in valvular heart disease and certainly not in patients with coronary artery disease. The studies of Spencer and many of his group30 have led to a newer concept of ventricular failure-that of 'a failure to empty rather than a failure to fill'. The normal ventricle generates sufficient force to maintain the ejection of blood against a wide range of impedance. Diseased ventricular muscle can generate sufficient force to maintain ejection in the face of low impedances, but sudden or sustained arteriolar constriction may cause a marked increase in the impedance to ejection, resuilting in reduced cardiac output together with increased diastolic volumes and pressures. By these criteria left ventricular failure occurs much more commonly than might be expected during anaesthesia-indeed, the responses shown in Figure 2 indicate the occurrence of
471
acute but transient left ventricular failure. Reversal of these changes may be brought about by the use of vasodilating drugs, the most commonly used being sodium nitroprusside given by slow intravenous infusion. By direct dilator effects on peripheral arterioles these drugs can reduce the impedance to left ventricular ejection without necessarily causing a marked reduction of arterial pressure, thus allowing the left ventricle to empty itself at a lower generated force and a lower myocardial oxygen cost. The result is a dramatic reduction of ventricular diastolic pressures, with resolution of electrocardiographic evidence of ischaemia. The applications of vasodilator therapy have increased considerably in the last two or three years3"` and will undoubtedly contribute to improvements in the peroperative management of patients with ischaemic heart disease.
Conclusion The purpose of this lecture has been to draw attention to the nature, extent, and influence of two disease states, hypertension and ischaemic heart disease, on the progress of patients presenting for anaesthesia and surgery. Over a period of 7 years the patterns have emerged which allow us to rationalize our handling of these patients, who are more at risk than others. The measures we adopt today are appropriate to our present knowledge and undoubtedly will improve the overall management of these patients. Twenty years ago it wvould have been unthinkable to anaesthetize and operate on patients with left ventricular failure. That we can do so now is a measure of the progress that has been made in the field of anaesthesia. I wish to express my gratitude to the many surgeons and physicians of the United Oxford Hospitals and to the graduate staff and technicians of the Nuffield Department of Anaesthetics, University of Oxford, without whose assistance and cooperation these studies could not have been performed. I also wish to thank the anaesthetic staff of the University of Califomia School of Medicine, San Diego, for their cooperation during studies of patients with severe ischaemic heart disease.
References I
Hales, S (I 727) Vegetable Staticks. (Republished 196I, London, Scientific Book Guild.)
472
C Prys-Roberts
2 Hales, S (I733) Statical Essays: Containing Haemastaticks. (Reprinted I964; No 22, History of Medicine Series, Library of New York Academy of Medicine. New York, Hafner Publishing.) 3 Bright, R (I827) Reports of Medical Cases, Selected with a View of Illustrating the Symptoms and Cure of Diseases, by a Reference to Morbid Anatomy. London, Longman. 4 Gull, W W, and Sutton, H G (i872) Medicochirurgical Transactions, 55, 273. 5 Mahomed, F A (I879) Guy's Hospital Reports (3rd series), 24, 363. 6 Volhard, F, and Fahr, T (1914) Die Brightsche Nierenkrankheit. Klinik, Pathologie, und Atlas. Berlin, Springer. 7 Sprague, H B (1929) Suirgery, Gynecology and Obstetrics, 49, 54. 8 Hickman, J, Livingstone, H, and Davics, M E (I935) Archives of Surgery, 3I, 917. 9 Peet, M M, and Isberg, E Ml (1946) Journal of the American Medical Association, 130, 467. io Sen, G, and Bose, K C (I 93 I) Indian Medical World, 2, I94. iI Dingle, H R (I966) Anaesthesia, 21, I51. 12 Hickler, R B, and Vandam, L D (1970) Anesthesiology, 33, 214. I3 Hollander, W B (I973) Circulation, 48, III2. 14 Tarhan, S, Moffitt, E A, Taylor, W F, and Giuliani, E R (I973) Journal of the American Medical Association, 220, 145 I. i 5 Mauney, F M jr, Ebert, P A, and Sabiston, D C jr (1970) Annals of Surgery, I72, 497. i6 Prys-Roberts, C, Meloche, R, and Foex, P (197I) British Journal of Anaesthesia, 43, 122. I 7 Prys-Roberts, C, Foex, P, Greene, L T, and Waterhouse, T D (1972) British Journal of Anaesthesia, 44, 335. i8 Prys-Roberts, C, Greene, L T, Meloche, R, and Foex, P (I97I) British Journal of Anaesthesia, 43, 531I
19 Prys-Roberts, C (1976) in Drug Interactions, cd Grahame-Smith, D. London, Macmillan. 20 Hoffman, J I E, and Buckberg, G D (I975) British MVedical Journal, I, 76. 21 Swan, H J C, Ganz, W, Forester, J, Marcus, H, Diamond, G, and Chonette, D (1970) New England Journal of Medicine, 283, 447. 22 Brunner, H R, Laragh, J H, Baer, L, Newton, M A, Goodwin, F T, Krakoff, L R, Bard, R H, and Buhler, F R (I972) New England Journal of Medicine, 286, 44. 23 Prys-Roberts, C, Foex, P, Biro, G P, and Roberts, J G (I973) British Journal of Anaesthesia, 45, 67I. 24 Viljoen, J F, Estafanous, G, and Kellner, G A (0972) Journal of Thoracic and Cardiovascular Surgery, 64, 826. 25 Alderman, E L, Coltart, D J, Wettach, G E. and Harrison, D C (I974) Annals of Internal Medicine, 8i, 625. 26 Miller, R R, Olsen, H G, Amsterdam, E A, and Mason, D T (I975) New England Journal of Medicine, 293, 4I 6. 27 Caralps, J M, Muilct, J, Wienke, H R, Moran, J M, and Pifarre, R (I974) Journal of Thoracic and Cardiovascular Surgery, 67, 526. 28 Kaplan, J A, Dunbar, R W, Bland, J W, Sumpter, R, and Jones, E L (I 975) Anesthesia and Analgesia, 54, 571. 29 Lappas, D, Lell, W A, Gabel, J C, Civetta, J M, and Lowenstein, E (1973) Anesthesiology,
38, 394.
30 Spencer, M P, Johnston, F R, and Denison, A B jr (1958) Circulation Research, 6, 491. 31 Shell, W E, and Sobel, B E (I974) New England Journal of Medicine, 29I, 48I. 42 Kouchoukos, N T, Sheppard, L C, and Kirklin, J W (1972) Journal of Thoracic and Cardiovascular Surgery, 64, 563. 33 Chatterjee, K, Parmley W W, Ganz, W, Forrester, J, Walinsky, P, Crexells, C, and Swan, H J C (I973) Circulation, 48, II83.
Medical problems of surgical patients Hypertension and ischaemic heart disease C Prys-Roberts DM FFARCS Nuffield Department of Anaesthetics, University of Oxford
Summary Pre-existing disease in the form of hypertension or ischaemic heart disease may increase morbidity and mortality in patients presenting for anaesthesia and surgery. The interaction of these two cardiovascular conditions in relation to anaesthesia has been studied in a series of II5 patients. The results did not support the view that antihypertensive drugs and /3receptor blocking agents should be withdrawn before anaesthesia and surgery. The main cause for concern in providing anaesthesia for these patients is that sympathetic nervous activation induced either by anaesthetic manoeuvres or by surgical stimulation may lead to reflex cardiovascular responses which, by increasing myocardial oxygen demand, lead to episodes of myocardial ischaemia. In this respect P-receptor blocking drugs appear to have a protective effect on the ischaemic myocardium.
Introduction Hypertension and ischaemic heart disease, afflictions which increase the risk of anaesthesia and surgery for patients who suffer from them, are phenomena of the 20th century. They were unkown at the time of William and John Hunter-indeed, little was then known about arterial pressure. At or about the time that John Hunter was born the Reverend Stephen Hales, curioius about the facts of nature and motivated to define 'the forces and velocity with which fluids are impelled', after determining with remarkable accuracy the force required to drive sap to the top of a tall tree', turned his attention to measuring the blood pressure of a conscious mare2. Hales also introdtuced the concept of peripheral resistance in the vascular system and, in experiments on intestinal blood vessels, showed that the main site of this resistance lay in the minute vessels Hunterian Lecture delivered on 7th April T976
of the gut wall. He strengthened the concept by showing that various agents, including brandy, could change the rate of flow of blood through these vessels. Hales's experimental work did not apparently influence any followers, and the rest of the i 8th and igth centuries were notable, at least in the field of fluid dynamics, for the great theoretical developments of Euler, Bernoulli, Navier, and Stokes. It was left to the Frenchmen Jean Louis Poiseuille and Etienne Jules Marey to measure blood flow and pressure in animals and to start the experimental validation of the theorists. Poiseuille introduced the UT-tube mercury manometer and, with Ludwig's float and pointer recording on a kymograph, started the process of arterial pressure measurement. The studies of Richard Bright3 into the aetiology of renal disease and the observations of Gull and Sutton4 relating Bright's disease to hyalin-fibroid formation in the walls of small arteries were related to the blood pressure measured in life only at a later date. Mahomed5, using crude methods for measuring blood pressure, showed that renal failure was only one outcome of Bright's disease and that death occurred more commonly from heart failure or cerebral haemorrhage secondary to high blood pressure. Thus began the period when the idea developed that high arterial pressure could exist independently of Bright's disease. Sustained high arterial pressure was known by a variety of names such as 'latent arteriosclerosis' (von Basch), 'hypertension permanente' (Huchard), and 'hyperpiesis' (Allbutt). The term coined by Frank was 'essentielle Hypertonie', a term which has remained with us as 'essential hypertension' even if the meaning is somewhat different. Frank used the term to imply that the high arterial pressure was 'essential' to overcome a
466
C Prys-Roberts
high peripheral resistance, whereas we now regard high arterial pressure as the result of flow into a high resistance. Finally, the monumental work of Volhard and Fahr' classified the various pathological causes of high arterial pressure, identifying renal and non-renal causes.
Until the 1920s pre-existing cardiac disease widely regarded as an absolute contraindication to surgery. In 1929 Sprague' found that the mortality in patients with cardiac disease subjected to surgery was highest in those with hypertension; 24 out of 75 died during or shortly after surgery, the majority succumbing to heart failure. It should be emphasized that Sprague's classification did not feature angina pectoris since it was considered even then an absolute contraindication to surgery. Seven years later Hickman, Livingstone, and Davies' described an operative mortality of I I/ in patients with hypertension but considered them a much better risk than those with angina pectoris, in whom the mortaity was 33%/0. This period saw the advent of the surgical treatment of hypertension and a dramatic improvement in mortality. While some centres, notably the Mayo Clinic, had an operative mortality of about 3 % in all patients, other centres recognized that a io% mortality was inevitable when a combined thoracolumbar sympathectomy was performed on patients with severe hypertension9, with a one-year survival of only was
54O/o. Drug therapy of hypertension started in Bose'" included hypertension amongst a number of conditions which were amenable to treatment with rauwolfia alkaloids, but it was not until the I950-60 period that drugs became popular in the management of hypertension. At this time little was known of the special risks involved in anaesthesia for the hypertensive patient and a controversy existed, which lasts to the present day, as to whether or not patients receiving antihypertensive drugs should have their therapy withdrawn for a period before anaesthesia and surgery. This controversy was international and interdisciplinary, since there anaesthetists, consensus among no was surgeons, or the physicians treating hyper193I, when Sen and
tensive patients as to either the nature and the extent of the risk involved in withdrawing antihypertensive therapy before surgery or the response of patients with high arterial pressure to anaesthesia. Widespread concern was expressed that antihypertensive drugs could disturb the maintenance of circulatory homoeostasis during surgery. Studies on the effects of anaesthesia in patients pretreated with rauwolfia alkaloids produced confficting results, and with the advent of more potent antihypertensive drugs there was scant information on the interactions of newer formns of therapy with the combined influence of anaesthesia and surgery. In their admirable reviews Dingle" and Hickler and Vandam" stresed the difficulties of reaching a rational conclusion to these issues, mainly owing to the paucity of information concerning the reactions to anaesthesia and surgery of treated and untreated hypertensive patients. Coronary artery disease and its consequences are the main complication associated with hypertension, pathological evidence of substantial coronary arterial lesions being found in more than 6o% of hypertensive patients at autopsy. Coronary artery disease is the major cause of death in hypertensive patients and is becoming predominant as other causes decline with successful antihypertensive therapy. Atherosclerosis affects the endothelial lining of major blood vessels, the primary lesion being the atheromatous plaque, which tends to narrow and occlude the arterial lumen, particularly at sites of vascular branching. There is abundant evidence in man and experimental animals that a sustained elevation of arterial pressure, regardless of its cause, aggravates and accelerates the development of the atherosclerotic process". The end result of coronary artery disease is myocardial infarction, a well-documented complication in the postoperative period'4. Most authors have identified pre-existing hypertension as a major factor in the development of intra- and postoperative myocardial ischaemia and of the subsequent myocardial infarction. Recurring themes in many of these discussions, particularly those in the American literature, have been the incidence, severity, and duration of intraoperative hypotension and the duration of surgery". Thus we are now familiar with
Medical problems of surgical patients
467
the coexistence of two disease states, hypertension and coronary artery disease, each of which may exist independently or aggravate the development of the other and both of which are common in older patients presenting for anaesthesia and surgery. When I commenced my studies of anaesthesia in relation to hypertension in I969 the questions seemed clear. Firstly, how did treated and untreated hypertensive patients respond to the induction and maintenance of anaesthesia, the surgical procedure, and the recovery from both? Secondly, was it possible to identify adverse cardiovascular responses to anaesthesia which could be related to preexisting antihypertensive therapy?
slow junctional rhythms (Fig. i) and was commoner in the presence of low arterial Pco2 induced by artificial ventilation. However, myocardial ischaemia also became evident in a number of hypertensive patients, both treated and untreated, if for any reason their arterial pressure rose dramatically during anaesthesia and surgery, commonly in response to: (i) laryngoscopy and endotracheal intubation'8; (2) bronchoscopy or tracheal suction; (3) surgical incision; (4) mesenteric traction; (5) aortic cross-clamping (aortoiliac surgery); or (6) recovery from anaesthesia. While it may be said that many of these reflex cardiovascular responses could be attenuated by deep anaesthesia, such a manoeuvre frequently induced sudden arterial Responses of hypertensive patients to hypotension as a result of junctional rhythm16 anaesthesia and surgery (Fig. 2). We began to recognize that preThe first pilot studies'6 indicated that patients disposition to myocardial ischaemia was a with untreated hypertension were less tolerant characteristic of many patients with untreated of anaesthesia than patients whose hyper- hypertension and of some treated hypertensive tension was well controlled and whose drug patients whose treatment was less than therapy was maintained up to and including adequate owing either to poor compliance with the day of surgery. Electrocardiographic drug taking on the patient's part or to evidence of myocardial ischaemia in the form inadequate medical attention. So the concept of flat ST-segment depression in the pre- developed that in this group of patients cordial leads was much commoner in un- impaired coronary arterial and myocardial treated hyertensives"6 17 and we were able perfusion could occur either because, during to relate this to periods of hypotension or hypotension, a normal myocardial oxygen hypertension during anaesthesia. When ST- demand exceeded a much reduced coronary segment depression, was associated with low blood flow or conversely because, during arterial pressure this was usually the result of hypertension and tachycardia, increased myo-
_ 1...4-
: .-:1-anaesthesia. (B) Responses to -..._ laryngoscopy and intubation-|--marked rise in arterial pressure and heart rate with onset of A-V
J.-
-1- -
A
B
AWAKE BEFORE ANAESTHESIA
DURING LARYIJGICOIf
-
1'-
-
C
D
FOLLOWING
MAINTENANE
INUBATIoN
HIG. I Adverse cardiovascular responses to anaesthesia in treated hypertensive patient. (A) Nornmal sinus rhythm with no evidence of myocardial ischaemia before
ANAEESIA
_-1:.
rhythm-contributing junctional to major increase in myocardial zvork resulting in mvocardial
ischaemia shown by flat, depressed ST segments in electrocardiogram. (C) Partial resolution of changes as arterial pressure and heart rate fall on completion of noxious stimulus. (D) Slow A-V junctional rhythm (isorhythmic dissociation) causing marked reduction of arterial pressure and further evidence of m10ocardial 1l.Chaen ia.
468
C Prys-Roberts
CMS
1:
| I--- '
ECf
.ji
1
load
~~: ARTERIAL PRESSURE
I
0S
mm Hg
PUILMONARY ARTERIAL
PRESSURE
Haemodynamic effects resulting from developof A-V junctional rhythm (isorhythmic dissociation) in patient with renovascular hypertension. Left-hand panel shows sinus rhythm (albeit with short P-R interval), high arterial pressure, and moderately elevated pulmonary capillary wedge pressure (balloon of Swan-Ganz catheter inflated at W) as indirect measure of left atrial pressure. Right-hand panel shows changes following onset of junctional rhythm causing 40% reduction of arterial pressure and rise of pulmonary capillary wedge FIG. 2 ment
pressure.
cardial
oxygen demand coronary blood flow.
exceeded the available
It also became apparent that those patients whose antihypertensive therapy had been maintained up to and including the period of surgery and whose arterial pressure was consequently closer to the normal range for their age showed fewer signs of physiological disturbances during induction and maintenance of anaesthesia. Furthermore, no adverse interactions have been observed between antihypertensive drugs and anaesthesic agents in any of the I I 5 patients who have been studied in depth so far, including 24 patients on high doses of 8-receptor blocking drugs"9. Our pilot studies led us to investigate in detail
these adverse cardiovascular anaesthesia and surgery, in particular the effects of different induction agents and their possible subsequent influence on the responses to laryngoscopy and endotracheal intubation. In comparisons of 7 induction agents or combinations in 48 patients the only more
responses
to
agents which appeared
unsatisfactory were diazepam and propanidid'8. However, all induction agents in doses which were considered appropriate for normal patients caused marked reductions of arterial pressure.
As a result of experience with patients with severe ischaemic heart disease undergoing coronary arterial bypass surgery I have modified my approach to induction olf anaesthesia in patients with hypertension. Fentanyl (3004oo0,g), which has little depressant effect on the cardiovascular system, is given intravenously followed by a small dose of thiopentone (25-50 mg) or I2 mg of Althesin (9 mg of alphaxalone + 3 mg of alphadolone acetate). In this way the depression of arterial pressure during induction can be minimized. Laryngoscopy and intubation of the trachea are stimuli which invoke reflex activation of the sympathetic nervous system to such a degree that significant hypertension and tachycardia occur even in normal, healthy patients. In patients with hypertension this response is exaggerated and very high arterial pressures may result"8 (Fig. 3). The combination of tachycardia and hypertension causes a major increase in myocardial work and therefore in myocardial oxygen demand. In patients with normal coronary vasculature this increased demand is easily satisfied and no adverse effects are apparent. In patients with coronary arterial disease, whether or not related to hypertension, such an increase in myocardial work may lead to acute impairment of oxygen supply to some areas of the myocardium supplied by diseased epicardial coronary arteries. This leads to dysrhythmia, ST-segment depression, and profound T-wave inversion, all signs of myocardial ischaemia (Figs. 3 and 4). A third factor in the genesis of myocardial ischaemia has become apparent more recently20. The subendocardial layer of the myocardium is the site in which collateral vessels develop in patients or animals whose epicardial vessels are atheromatous. These subendocardial collateral vessels, which supply adjacent endocardial and middle cardiac layers, are thinwalled and chronically dilated because of the low oxygen tension in this layer of the myocardial shell, which incidentally has the highest developed tension dturing contraction of any part of the myocardium. Consequently these collaterals may be easily compressed by high intracavitary pressure in the left ventricle, particularly during diastole, leading to impaired distribution of blood flow to the
Medical problems of surgical patients
469
20
RIGHT ATRIAL PRESSURE
mm Hg
't:
10
I; .. I.I 1, .~ o L±-4--[L-
250 200 1.
PRESSE nun Hg
100 1
0
L
L
I
_
i.
I-F -i
.1
I-
F7a--- L;~~ _1~~ 1 .L rTi F i I i, t'I -t - i-*, t-- t: t t - }-|
A -7 A
A: A-A-
-.t
-4-
t - 4
1
i.
1
1- --
lt
t
I.
i...
--l
~~~~~~~~~~~~~~~~~.;
FIG. 3 Haemodynamic responses of treated hypertensive patient to induction of anaesthesia followed by laryngoscopy and endotracheal intubation. At first arrow anaesthesia was induced with fentanyl (200 g,g) and thiopentone (ioo mg) and muscle relaxation obtained with pancuronium (6 mg). Anaesthesia was maintained with nitrous oxide (50%) and oxygen. At second arrow insertion of laryngoscope and endotracheal intubation caused marked hypertension, tachycardia and dysrhythmia associated with elevation of pulmonary capillary wedge pressure.
i
i- A-4t-4v t --1I ....I t
........ :
_..
20 r
PULKWMmI AMTESIAL WESUE
PRSSURE m g
15
-
10
-
5
i;
_. ..._. ... _. v....._ _.--'-t..
.^
OL 200
.. .. RATE
4 -
-l .... ........
-1- : j e
t * t~ ~ ~-~.i.!.tl.... -~ ~-i -
-t:'.-W :-:f:
|
:
0 *--
IT10 L
t- $ st~~~~~~~~~~~~~~~~
_t
p
~~~.-.
...t- .-i :---:.
....t.. 4i11
_----+iw............ ....... ......
-' '''~~~~~~~~~~~~~~~~~~.. A'6
....
-;t,-i---
-..i
--
...;;........... ...-.......
adjacent myocardium. That such high intracavitary pressures can occur during diastole has become apparent only with the advent of
drugs, increased sympathetic neurogenic activity at a-adrenergic nerve endings, or, in patients with renovascular hypertension, the Swan-Ganz balloon-tipped pulmonary circulating angiotensin formed as a result of artery catheter21, allowing indirect monitoring increased plasma renin levels22. of left atrial pressure (Fig. 2). High ventricular diastolic pressures indicate acute left Management of adverse effect ventricular failure in that the ventricle is Regardless of the causation of the increased incapable of developing sufficient force to myocardial work, the measures which we eject blood completely against a major might adopt to prevent this adverse effect in increase of systemic vascular resistance, the susceptible patients may be classified as latter resulting from arteriolar constriction. follows: Arteriolar constriction may be caused by (i) Suppression of noxious stimuli which Time.
sacs.
E.C.G. Lad U1 s Rae 60c per min. 40
Hurt
Orachial
IS.0.
Artery
Pressure 1t3 mm Hg..
oj Pulmonary
20
Artery Pressure mm
Hg.
ol Awake enesthesia
Befure
2 minutes after ntubetlon
mntnrachlu
10 minutes alter intubation 69*N20. 30%* 2 1% Halothane.
FIG. 4 Dysrhythmia and myocardial ischaemia developing as a result of hypertension and tachycardia in response to laryngoscopy and endotracheal intubation. The very high diastolic values of pulmonary arterial pressure during the period of bidirectional junctional tachycardia (centre panel) caused myocardial ischaemia, the ischaemic changes (depressed ST segment and inverted T waves: right-hand panel) persisting after resolution of the hypertension, tachycardia, and dysrhythmia. (Reprinted from the British Journal of Anaesthesia by permission of the publishers.)
470
C Prys-Roberts
may invoke reflex sympathetic activity by the use of local anaesthesia at the site of the noxious stimulus, deep levels of anaesthesia, or high doses of analgesic drugs.
(2) Suppression of the effector end-organs of the sympathetic nervous system, particularly those of the heart, by the use of 8-receptor blocking drugs.
(3) Limitation of the ability of the myocardium to increase its work and thus its oxygen demand, again by the use of P-receptor blocking drugs. (4) Reduction of left ventricular ejection load by vasodilator agents-for example, sodium nitroprusside, trimetaphan, hydrallazine-and a-adrenergic receptor blockers in certain appropriate conditions such as phaeochromocytoma. I would like to devote the remainder of this lecture to dealing with two of these measures to combat myocardial ischaemia; the use of [8receptor blocking drugs and the use of vasodilator drugs. Both are highly relevant to the management of hypertension and ischaemic heart disease since P-receptor blockers are rapidly becoming the predominant drugs in antihypertensive therapy and are already widely used in the management of angina pectoris and myocardial infarction. Many patients receiving large doses of P-receptor blockers are now presenting for anaesthesia and surgery, but despite growing experience with the pharmacology of these drugs there are many anaesthetists and surgeons who are reluctant to accept these patients for surgery.
have their propranolol therapy withdrawn at least two weeks before surgery24. Sudden withdrawal of 8-receptor blockers in patients with ischaemic heart disease may precipitate severe angina and even myocardial infarction25' 26; thus it is imperative that any withdrawal of these drugs should be gradual. However, recent studies of patients undergoing cardiopulmonary bypass27 28 have not confirmed earlier fears and have not documented any adverse reactions in patients on preexisting propranolol therapy. Our studies23 showed that in hypertensive patients deliberately pretreated with practolol* the hypertension and tachycardia associated with laryngoscopy and intubation were greatly attenuated and no dysrhythmia or de novo electrocardiographic evidence of myocardial ischaemia was seen in any of the 23 patients initially studied. This was in marked contrast to the incidence of dysrhythmia (4I %) and myocardial ischaemia (38%) observed in hypertensive patients who had not received 8receptor blockers18. There was no evidence that P-receptor blockers impaired cardiovascular performance in these patients; indeed, values of arterial pressure and cardiac output were slightly higher throughout anaesthesia than in hypertensive patients receiving what was then regarded as more conventional therapy. In a more recent study of patients with renovascular hypertension receiving doses of propranolol or other P-receptor blockers in doses between 240 and 2000 mg per day no serious adverse reactions were observed during anaesthesia and prolonged vascular surgery despite the severity of their disease state. I think it is now reasonable to conclude that for patients with hypertension or ischaemic heart disease maintenance of 8-receptor blocking therapy through the period of anaesthesia and surgery, far from causing adverse reactions, may be beneficial. Vasodilators While P-receptor blockade may be regarded as a prophylactic measure, the use of vasodilator drugs to reduce the impedance to left ventricular ejection must be regarded as a therapeutic measure in
Beta-receptor blockers My colleagues and I23 investigated the effects of 8-receptor blocking drugs in hypertensive patients for two reasons: firstly to find out whether these drugs would attenuate the sympathetic response to laryngoscopy and endotracheal intubation, and secondly to identify any adverse drug interactions occurring during anaesthesia. The second question has been particularly relevant in patients undergoing coronary arterial bypass *Practolol has now been withdrawn from general use surgery since it was proposed, largely on owing to the high incidence of side effects on the anecdotal evidence, that such patients should skin, eyes, and peritoneum.
Medical problems of surgical patients
patients with left ventricular failure. In the past left ventricular failure has been recognized by its traditional symptoms and signs. Nowadays, thanks to improved technology, we can define left ventricular failure in numerical terms and we can discriminate finer degrees of left ventricular failure than could be detected hitherto. In this respect the application of the Swan-Ganz balloon-tipped catheter29 for measuring pulmonary capillary w,Tedge pressure has enabled us to recognize the acute development of left ventricular failure and to apply the appropriate measures to treat it. The traditional concept defined left ventricular failure as an inability of the ventricle to maintain its output despite an elevated filling pressure, the implication being that, owing to a failure to generate sufficient force, the ventricle was unable to cope with venous return. A corollary of this view was that the treatment of left ventricular failure was based on the use of drugs such as cardiac glycosides, which exerted a positive inotropic effect, and diuretics, which reduced the peripheral or pulmonary oedema. Acute pump failure following cardiopulmonary bypass or in the acute phase of myocardial infarction was usually treated with adrenergic drugs having a positive inotropic effect. The disadvantage of this approach is that the treatment involves an increase in myocardial work, hardly acceptable in valvular heart disease and certainly not in patients with coronary artery disease. The studies of Spencer and many of his group30 have led to a newer concept of ventricular failure-that of 'a failure to empty rather than a failure to fill'. The normal ventricle generates sufficient force to maintain the ejection of blood against a wide range of impedance. Diseased ventricular muscle can generate sufficient force to maintain ejection in the face of low impedances, but sudden or sustained arteriolar constriction may cause a marked increase in the impedance to ejection, resuilting in reduced cardiac output together with increased diastolic volumes and pressures. By these criteria left ventricular failure occurs much more commonly than might be expected during anaesthesia-indeed, the responses shown in Figure 2 indicate the occurrence of
471
acute but transient left ventricular failure. Reversal of these changes may be brought about by the use of vasodilating drugs, the most commonly used being sodium nitroprusside given by slow intravenous infusion. By direct dilator effects on peripheral arterioles these drugs can reduce the impedance to left ventricular ejection without necessarily causing a marked reduction of arterial pressure, thus allowing the left ventricle to empty itself at a lower generated force and a lower myocardial oxygen cost. The result is a dramatic reduction of ventricular diastolic pressures, with resolution of electrocardiographic evidence of ischaemia. The applications of vasodilator therapy have increased considerably in the last two or three years3"` and will undoubtedly contribute to improvements in the peroperative management of patients with ischaemic heart disease.
Conclusion The purpose of this lecture has been to draw attention to the nature, extent, and influence of two disease states, hypertension and ischaemic heart disease, on the progress of patients presenting for anaesthesia and surgery. Over a period of 7 years the patterns have emerged which allow us to rationalize our handling of these patients, who are more at risk than others. The measures we adopt today are appropriate to our present knowledge and undoubtedly will improve the overall management of these patients. Twenty years ago it wvould have been unthinkable to anaesthetize and operate on patients with left ventricular failure. That we can do so now is a measure of the progress that has been made in the field of anaesthesia. I wish to express my gratitude to the many surgeons and physicians of the United Oxford Hospitals and to the graduate staff and technicians of the Nuffield Department of Anaesthetics, University of Oxford, without whose assistance and cooperation these studies could not have been performed. I also wish to thank the anaesthetic staff of the University of Califomia School of Medicine, San Diego, for their cooperation during studies of patients with severe ischaemic heart disease.
References I
Hales, S (I 727) Vegetable Staticks. (Republished 196I, London, Scientific Book Guild.)
472
C Prys-Roberts
2 Hales, S (I733) Statical Essays: Containing Haemastaticks. (Reprinted I964; No 22, History of Medicine Series, Library of New York Academy of Medicine. New York, Hafner Publishing.) 3 Bright, R (I827) Reports of Medical Cases, Selected with a View of Illustrating the Symptoms and Cure of Diseases, by a Reference to Morbid Anatomy. London, Longman. 4 Gull, W W, and Sutton, H G (i872) Medicochirurgical Transactions, 55, 273. 5 Mahomed, F A (I879) Guy's Hospital Reports (3rd series), 24, 363. 6 Volhard, F, and Fahr, T (1914) Die Brightsche Nierenkrankheit. Klinik, Pathologie, und Atlas. Berlin, Springer. 7 Sprague, H B (1929) Suirgery, Gynecology and Obstetrics, 49, 54. 8 Hickman, J, Livingstone, H, and Davics, M E (I935) Archives of Surgery, 3I, 917. 9 Peet, M M, and Isberg, E Ml (1946) Journal of the American Medical Association, 130, 467. io Sen, G, and Bose, K C (I 93 I) Indian Medical World, 2, I94. iI Dingle, H R (I966) Anaesthesia, 21, I51. 12 Hickler, R B, and Vandam, L D (1970) Anesthesiology, 33, 214. I3 Hollander, W B (I973) Circulation, 48, III2. 14 Tarhan, S, Moffitt, E A, Taylor, W F, and Giuliani, E R (I973) Journal of the American Medical Association, 220, 145 I. i 5 Mauney, F M jr, Ebert, P A, and Sabiston, D C jr (1970) Annals of Surgery, I72, 497. i6 Prys-Roberts, C, Meloche, R, and Foex, P (197I) British Journal of Anaesthesia, 43, 122. I 7 Prys-Roberts, C, Foex, P, Greene, L T, and Waterhouse, T D (1972) British Journal of Anaesthesia, 44, 335. i8 Prys-Roberts, C, Greene, L T, Meloche, R, and Foex, P (I97I) British Journal of Anaesthesia, 43, 531I
19 Prys-Roberts, C (1976) in Drug Interactions, cd Grahame-Smith, D. London, Macmillan. 20 Hoffman, J I E, and Buckberg, G D (I975) British MVedical Journal, I, 76. 21 Swan, H J C, Ganz, W, Forester, J, Marcus, H, Diamond, G, and Chonette, D (1970) New England Journal of Medicine, 283, 447. 22 Brunner, H R, Laragh, J H, Baer, L, Newton, M A, Goodwin, F T, Krakoff, L R, Bard, R H, and Buhler, F R (I972) New England Journal of Medicine, 286, 44. 23 Prys-Roberts, C, Foex, P, Biro, G P, and Roberts, J G (I973) British Journal of Anaesthesia, 45, 67I. 24 Viljoen, J F, Estafanous, G, and Kellner, G A (0972) Journal of Thoracic and Cardiovascular Surgery, 64, 826. 25 Alderman, E L, Coltart, D J, Wettach, G E. and Harrison, D C (I974) Annals of Internal Medicine, 8i, 625. 26 Miller, R R, Olsen, H G, Amsterdam, E A, and Mason, D T (I975) New England Journal of Medicine, 293, 4I 6. 27 Caralps, J M, Muilct, J, Wienke, H R, Moran, J M, and Pifarre, R (I974) Journal of Thoracic and Cardiovascular Surgery, 67, 526. 28 Kaplan, J A, Dunbar, R W, Bland, J W, Sumpter, R, and Jones, E L (I 975) Anesthesia and Analgesia, 54, 571. 29 Lappas, D, Lell, W A, Gabel, J C, Civetta, J M, and Lowenstein, E (1973) Anesthesiology,
38, 394.
30 Spencer, M P, Johnston, F R, and Denison, A B jr (1958) Circulation Research, 6, 491. 31 Shell, W E, and Sobel, B E (I974) New England Journal of Medicine, 29I, 48I. 42 Kouchoukos, N T, Sheppard, L C, and Kirklin, J W (1972) Journal of Thoracic and Cardiovascular Surgery, 64, 563. 33 Chatterjee, K, Parmley W W, Ganz, W, Forrester, J, Walinsky, P, Crexells, C, and Swan, H J C (I973) Circulation, 48, II83.
