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Controlled Hypotension
Controlled Hypotension EDWARD F. DAW, M.D. EDWARD P. DIDIER, M.D. RICHARD A. THEYE, M.D.
HISTORY
Over the past 100 years or so, bleeding by leech or lancet has been replaced by an active concern for prevention of blood loss. This change in attitude is based in large part on greater awareness of the relationship between unreplaced blood loss and morbidity. In the past, blood loss during surgery was minimized through the use of the ligature, the pack, the hemostat, and the tourniquet, complemented of course by various drugs, astringents, and electrical devices. Among the more recent methods is controlled or induced hypotension, wherein the objective is to produce a relatively bloodless field or to reduce the effusion of blood by deliberately reducing the hydrostatic pressure in the vessels at the operative site. Gardner is credited with the first direct approach to the problem. In this approach a state of deliberate hemorrhagic shock was induced by arteriotomy and blood removal during the critical period of surgical excision of an intracranial lesion. Mter removal of the lesion, blood volume and pressure were restored to normal by reinfusion of the blood previously removed. In 1948, Griffiths and Gillies reported a method of reducing blood pressure by total subarachnoid block, and Bromage, in 1951, reported on hypotension produced by epidural anesthesia. At about the same time the use of various ganglionic blocking drugs2 , 5, 20 was becoming popular for the production of hypotension, and the advantage of controllability was emphasized. During this period Enderby 5, 6 pointed out the importance of gravitational effects, both good and bad, and suggested means of using them to advantage. These developments, although appearing to be new, were preceded by earlier references to the benefits and hazards of various anesthetic techniques and maneuvers which minimized bleeding and thereby provided more optimal surgical conditions. In fact, many of these earlier suggestions 1003
1004
EDWARD
F.
DAW, EDWARD
P.
DIDIER, RICHARD
A.
THEYE
are now considered important basic considerations in successful application of controlled hypotension. French, in 1912, discussed the advantages of his chair table in tonsillectomy under ether anesthesia and stated as follows: "There is less shock, and less disturbance in other ways, to the patient after operation because less ether is required to maintain narcosis when the sitting posture has been attained. This is, no doubt, due to the diminished blood pressure in the vessels of the head when the body is in the upright position and under the influence of a general anesthetic." Similarly, Morton, in 1903, reported a case of resection of the maxilla under cocaine spinal anesthesia, and he commented on the lack of shock in the awake patient and the excellence of the surgical field. Many other early clinicians were aware of some of the factors now considered as part of the technique of controlled hypotension, such as selection of chloroform versus ether, deep versus light anesthesia, position, and hyperventilation. 12 Despite this background, acceptance of the technique of controlled hypotension was limited and was viewed generally as a physiologic trespass until the introduction of the ganglionic blocking agents. With these drugs it became possible to reduce arterial pressure without the morbidity and hazard of hemorrhagic shock by arteriotomy and to avoid the technical problems and physiologic alterations of high spinal anesthesia. The drugs used for this purpose include pentamethonium, hexamethonium, trimethaphan camphorsulfonate, and sodium nitroprusside; this listing is approximately in the order of decreasing duration of activity and chronology of introduction of these agents.
METHODS OF PRODUCING HYPOTENSION
Three methods of reducing arterial blood pressure have been used: nonreplacement of blood and fluids, deliberate depression of the circulatory system by overdosage of anesthetic agent, and ganglionic or adrenergic blockade. All have in common the goal of diminished arterial bleeding in order to miniInize blood loss or to maintain visibility of the surgical field.
Nonreplacement of Blood and Fluids Arterial pressure may be lowered to hypotensive ranges by limiting replacement of blood and fluids during a period of massive blood loss. The reduction of arterial pressure, and thereby of volume of bleeding, may provide sufficient surgical exposure and time for the surgeon to gain control of the bleeding vessel. This technique, like arteriotomy, must be considered as essentially one of hemorrhagic and hypovolemic shock19 and is justified only in certain desperate surgical situations in which other approaches are deemed unsuitable.
Anesthetic Circulatory Depression Administration of increased concentrations of a potent anesthetic
CONTROLLED HYPOTENSION
1005
agent results in a lowering of blood pressure both by peripheral vasodilatation and by direct myocardial depression and subsequent reduction in cardiac output. This technique may safely be imposed only for short periods of moderate levels of hypotension, since the danger of severe depression and circulatory arrest is ever present. Halothane is probably the most convenient agent to use for this maneuver, because of its extreme potency, rapid onset of action and profound depression of the cardiovascular system. In addition, the administration of halothane is not associated with increased sympathetic nervous system activity or release of increased amounts of epinephrine and norepinephrine.
Ganglionic or Adrenergic Blockade Ganglionic or adrenergic blocking results in a lowering of arterial blood pressure when the reduction in peripheral resistance is achieved without a concomitant increase in cardiac output. This effect was accomplished in the past by blocking the sympathetic outflow by total subarachnoid or epidural block. The modern approach is to employ blocking agents. The drugs most often used are trimethaphan and hexamethonium. Other drugs which have been used include sodium nitroprusside, pentamethonium, tetraethyl ammonium, homatropinium, and pentolinium. 1. Trimethaphan (Arfonad) is the ganglionic blocking agent most commonly used in this country. The ease of inducing and controlling the degree of hypotension by means of an intravenous drip makes trimethaphan more suitable than a single-injection drug. Trimethaphan is usually administered as a 0.1 or 0.2 per cent solution; the speed of infusion determines the rate of the developing hypotension and the ultimate hypotensive level. Trimethaphan produces its action partly through competition with acetylcholine at the cholinergic receptor in the ganglion. The rapid and transient action of trimethaphan is due to its partial destruction by the enzyme cholinesterase. Some part of the hypotension produced may be due to histamine release. Circulatory compensatory mechanisms in patients receiving trimethaphan are greatly depressed; thus, any change in position should be accomplished before and not after the induction of hypotension. The hypotension produced with trimethaphan may be quickly reversed by the injection of a peripherally acting vasopressor. Along with the arterial hypotension there is often an increase in the heart rate. Provided that other circulatory depressant agents are absent, cardiac output may be affected little and peripheral resistance may be lowered. Pupillary dilatation occurs, presumably because the tonic parasympathetic function of the ciliary ganglion is blocked by the drug. The pupillary light reflex is abolished or diminished, as is accommodation of the pupil to near vision. The pupillary disturbance can interfere with the neurologic assessment of the patient postoperatively and it may be of concern to the patient, because of difficulty of vision due to the persistent pupillary dilatation. 2. Nearly all of the drugs of the methonium group have some gangli-
1006
EDWARD
F.
DAW, EDWARD
P.
DIDIER, RICHARD
A.
THEYE
onic blocking properties. It is characteristic of this group that as the straight chain of the drug increases in length, the ganglionic blocking properties become less pronounced and the drugs begin to assume curarelike properties. Thus, decamethonium (C-IO) is used clinically as a skeletal muscle relaxant and displays little evidence of ganglionic blocking properties. Hexamethonium (C-6), a quaternary ammonium compound, presumably produces hypotension through competition with acetylcholine at the ganglion site. The dosage varies according to the requirement of each patient and the degree of hypotension desired. Usually a small dose of 5 to 10 mg. is administered, and the individual response is noted; if no unusual response occurs, 25 to 50 mg. may be injected at the time hypotension is desired. Rarely, profound levels of hypotension may develop after the injection of the initial test dose of 5 to 10 mg. The response of the patient to the injected dose of hexamethonium may be varied by a change of position and by small reductions of blood volume. The hypotensive state may last 45 to 60 minutes. The level of the hypotension induced by hexamethonium can be modified by small repeated injections of a peripherally acting vasopressor. The hypotension-producing properties of tetraethyl ammonium (TEA; Etamon) have been known since 1914. The drug presumably acts by blocking the nicotinic action of acetylcholine. l1 Tetraethyl ammonium is usually injected intravenously in doses of 200 to 400 mg. Because of its prolonged action, this drug has very little use in clinical anesthesia. Pentamethonium (C-5) is another of this general methonium group and has been successfully used for the induction of hypotension. The uses and characteristics of the drug are similar to those of hexamethonium. 3. Sodium nitroprusside has been used clinically. Intravenous administration produces a rapid fall in blood pressure, presumably by the direct dilating action of the drug on the vessel wall. The hypotension is of such short duration that continuous infusion may be required. 7
PHYSIOLOGIC CONSIDERATIONS WITH INDUCED HYPOTENSION
As with any technique used to alter physiologic function, the advantages to the surgeon and the potential hazards to the patient must be considered together. In addition, not only the degree but also the duration of the period of induced hypotension must be taken into account. Low levels of perfusion pressure may not be tolerated well for even short periods of time, while moderate levels of perfusion may be tolerated for longer periods of time. Moyer and Morris presented evidence of decreased cerebral oxygen uptake during episodes of hypotension induced with hexamethonium. These reductions of cerebral oxygen uptake were coincidental with a decrease in cerebrovascular resistance. They found that as cerebral blood flow and
CONTROLLED HYPOTENSION
1007
oxygen uptake in the brain decreased there was an mcrease in the cerebral arterial-venous oxygen difference and a decrease in cerebral oxygen consumption. With the reversal of the hypotensive state by means of vasopressors, arterial blood pressure, cerebral blood flow, cerebral vascular resistance, and cerebral oxygen consumption all increased. With these changes in vascular dynamics, there was no change in cerebral metabolites indicative of hypoxic episodes. Van Bergen and associates noted a decrease in the voltage and fast activity on the electroencephalogram as the blood pressure fell. At arterial blood pressures of 50 mm. Hg and below, no surface electrical activity was obtained. The administration of vasopressors resulted in a return of electrical activity coincidental with the elevation of the arterial pressure. The appearance of an abnormal electroencephalographic pattern appears to be dependent on the speed of induction and on the degree of the hypotension. 21 Regardless of the level of hypotension produced by drugs, if the electroencephalogram should begin to show abnormal patterns-that is, high-voltage slow activity (delta waves)-or if periods of electrical inactivity develop, the hypotensive state should be reversed. Since the perfusion rate of the myocardium via the coronary arteries is directly related to the arterial diastolic pressure, there is a danger of myocardial ischemia as pressure is reduced. Electrocardiographic monitoring during the hypotensive state is therefore essential, particularly in patients with a history of myocardial or coronary insufficiency (or both). Changes in the rhythm and in the T-wave configuration and ST segment are helpful in detecting myocardial ischemia. In the same manner, any reduction in the hepatic artery perfusion pressure may compromise oxygenation of hepatic tissue. Hepatic blood flow may be reduced as much as 33 per cent during periods of induced hypotension. There have been reports of altered hepatic function and even hepatic failure after halothane anesthesia during which hypotensive episodes occurred. The effects of induced hypotension on the kidneys is difficult to assess. As arterial pressure is reduced, renal filtration decreases. All effective renal filtration may cease at levels of 70 mID. Hg. Even though renal filtration ceases, there is evidence that the decrease in vascular resistance as a result of the hypotension allows renal blood flow to be little affected. 16 Although the effects of lowered arterial blood pressure on only the brain, heart, liver, and kidney have been considered, it is to be remembered that physiologic function of all tissues and organs, and of the body as a whole, may be altered during induced hypotension. 19 In this regard, recent hemodynamic and metabolic studies during induced hypotension at the Mayo Clinic are of interest. 23 • 24 These observations were made in unpremedicated, paralyzed, supine patients artificially ventilated during varicose vein surgery with ether (five patients) or halothane (six patients) anesthesia. Two sets of observations were made before, during, and after 30 minutes of arterial hypotension induced with controlled amounts of trimethaphan given intravenously. The results are summarized in Table 1.
Table 1.
O.
PRESSURE, MEAN
(mm. Hg) CARDIAC OUTPUT
Arterial
With halothane anesthesia Before During
Arfonad
After With ether anesthesia Before
I r
Admd During After
,... = ~
Hemodynamics and Metabolism Before, During, and After Use of Arfonad with Halothane and with Ether Anesthesia: Average (and Range)
Right atrial
(L./min./m. 2)
HEART RATE, BEATS/ MIN.
STROKE
O.
VOLUME
UPTAKE
(ml./beat/m. 2) (ml./min./m. 2 )
SATURATION
(per cent)
SYSTEMIC RESISTANCE
Mixed venous
Right atrial observed
(dynes sec. cm. -5) trJ
I:j
~ 87 (72-101)
8 (4-12)
2.6 (2.2-3.1)
84 (78-90)
32 (26-36)
59 (47-71)
7 (5-9)
2.4 (2.0-2.9)
86 (80-93)
28 (23-32)
80 (66-99)
9 (5-12)
2.5 (2.0-2.9)
73 (65-84)
35 (27-41)
105 (81-123)
79 (77-82)
76 (72-77)
1390 (980-1850)
96 (76-115)
78 (74-79)
72 (66-78)
1000 (770-1250)
103 (83-120)
78 (73-81)
74 (70-75)
1290 (900-1440)
~
tJ
~~
trJ I:j
~
~
tJ
8
87 (66-117)
10 (6-12)
2.9 (2.3-3.5)
77 (60-102)
38 (34-42)
116 (110-120)
80 (75-85)
78 (72-85)
1140 (840-1390)
60 (52-71)
9 (5-12)
2.7 (2.3-3.5)
84 (68-117)
32 (30-35)
108 (101-113)
80 (73-84)
74 (67-86)
800 (570-990)
o
95 (77-120)
9 (5-11)
3.4 (3.1-3.8)
82 (69-109)
40 (35-43)
114 (109-119)
83 (79-85)
80 (78-83)
1190 (1020-1390)
?--
[;j
JtI ~
~
~
(Reproduced with permission from Tuohy, G. F. and Theye, R. A.: Effect of trimetaphan and haemodynamics and oxygen consumption during halothane anaesthesia in man. Brit. J. Anaesth. 37:144-151 [March] 1965.)
~
~
CONTROLLED HYPOTENSION
1009
It is apparent that trimethaphan was effective in inducing a similar degree of hypotension with either halothane or ether. The hemodynamic recovery, however, was more vigorous during anesthesia with ether than with halothane. The lowering of arterial pressure was achieved primarily by reduction in peripheral vascular resistance. Changes in cardiac output with trimethaphan were small, not entirely consistent, and probably functionally insignificant. Since stroke volume always fell significantly with trimethaphan, it follows that an increasing heart rate serves an important role in maintaining cardiac output during administration of trimethaphan. Oxygen uptake fell with induced hypotension. The changes in cardiac output and oxygen uptake were similar in degree and direction so that mixed venous oxygen levels were not changed significantly. Thus, over-all, no profound or significant alterations in the whole-body oxygen transport system were found to occur with induced hypotension in these studies.
CLINICAL APPLICATION
Ditzler's recent survey of leading American medical institutions suggests that the primary indication for use of induced hypotension presently is the facilitation of surgery. Earlier, Ditzler and Eckenhoff had observed that in the two types of operations investigated there was a significant conservation of blood (20 to 35 per cent) but an increase in the duration of the operation. At the Mayo Clinic the experience with controlled hypotension during radical mastectomyl5. 22 suggests that facilitation of surgery is a suitable indication for the use of a safe technique for hypotension, that increased morbidity and mortality associated with controlled hypotension arise from errors in technique or from improper selection of patients, and that, in a general sense, those factors that are advantageous to the surgeon are of benefit to the patient. Thus, in practice, the use of controlled hypotension is indicated primarily by considerations of facilitating operations, minimizing blood loss during operation, or permitting operations not otherwise possible.1 3 Accordingly, induced hypotension may be of value in the operative treatment of intracranial aneurysms and large vascular intracranial tumors, certain cardiovascular procedures, radical head and neck surgery, the fenestration operation,14 and radical mastectomy.
PRECAUTIONS AND CONSIDERATIONS IN THE USE OF INDUCED HYPOTENSION
There are probably many relative and few absolute contraindications to the use of induced hypotension. If a major surgical procedure is deemed
1010
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F.
DAW, EDWARD
P.
DIDIER, RICHARD
A.
THEYE
necessary in the presence of myocardial, renal, or hepatic disease, and if indications for the use of induced hypotension exist, these techniques can probably be used. The amount of reduction should not be arbitrary but rather should be tailored to meet the needs of the operation without undue hazard to the patient. In many patients, reduction of arterial pressure to 90 to 100 mm. Hg may be just as effective in reducing the degree and force of blood loss as reduction to 60 to 70 rom. Hg. Patients in whom hypotensive techniques are to be used should be monitored by the electrocardiogram and probably the electroencephalogram, as previously discussed, and by central venous and intra-arterial blood pressure recording if these techniques are available. The pattern of change in central venous pressure may serve as a guide to fluid volume replacement. During techniques of hypotension, with the blood pressure maintained by constant infusion of ganglionic blocking agents, guides to blood replacement therapy may be inadequate or absent. A rising or falling venous pressure, in the presence of unchanged myocardial function, usually is indicative of the status of fluid and blood replacement. Certain precautions should be observed when hypotension is induced with ganglionic blocking agents. A vasopressor should be instantly available for use in reversal of the hypotension. Rates of infusion should be controlled precisely, and the infusion line, when not needed, should be disconnected from the infusion needle or should be secured with a metal clamp. Mter termination of the hypotensive period, the infusion set should be discarded. The position of the patient should remain stable, although minor variations of position may be used to alter the level of arterial pressure. It should be remembered that the blood pressure recorded at the site of an arterial needle or arm cuff may be considerably higher than that at the level of the cerebral circulation. Enderby 6 found that for every inch the head is elevated above the level of the heart, the cerebral perfusion pressure is reduced 2 rom. Hg in relation to the pressure at heart level. A critical level of pressure that maintains capillary perfusion has been determined to be 32 mm. Hg. In addition, blood flow to critical areas such as the head may be reduced because of the elastic quality of small vessels and local tissue compression due to tumor mass, hemorrhage, or retraction. Because external pressure may increase the critical opening pressure of the arterioles, levels of induced hypotension must not be as low as usual in the presence of increased intracranial pressure. Some prefer to use moderate surface hypothermia (32 0 to 300 C.) in conjunction with induced hypotension in order to offer some protection against the reduced tissue perfusion that prevails during hypotension.
SUMMARY
The use of controlled hypotension may be indicated for some surgical
1011
CONTROLLED HYPOTENSION
procedures, which include intracranial and cardiovascular operations, radical head and neck surgery, radical mastectomy, and fenestration procedures. Morbidity and mortality attributed to controlled hypotension has been the result of improper and injudicious use. When this technique is used properly, overall morbidity and mortality could be less for these procedures than that expected if the advantages of controlled hypotension were not obtained. In this institution trimethaphan (Arfonad) is the drug of choice for controlled hypotension. The rapidity and short duration of action of trimethaphan produce an easily controlled level of arterial hypotension. As arterial hypotension is produced, tissue perfusion must diminish. The levels of arterial hypotension should be equated with time to assess possible compromise of the cerebral, hepatic, renal, and coronary blood flows. Because controlled hypotension, properly applied, offers definite advantages to the surgical procedure and is to the benefit of the patient, this technique has a definite place in anesthesia-surgical practice.
REFERENCES 1. Bromage, P. R.: Vascular hypotension in 107 cases of epidural analgesia. Anaesthesia 6:26-29 (Jan.) 1951. 2. Davison, M. H. A.: Pentamethonium iodide in anaesthesia. Lancet 1 :252-253 (Feb. 11) 1950. 3. Ditzler, J. W.: Current status of deliberately induced hypotension. Anesth. & Analg. 43:116-120 (Jan.-Feb.) 1964. 4. Ditzler, J. W., and Eckenhoff, J. E.: Comparison of blood loss and operative time in certain surgical procedures completed with and without controlled hypotension. Ann. Surg. 143:289-293 (March) 1956. 5. Enderby, G. E. H.: Controlled circulation with hypotensive drugs and posture to reduce bleeding in surgery: Preliminary results with pentamethonium iodide. Lancet 1:1145-1147 (June 24) 1950. 6. Enderby, G. E. H.: Postural ischaemia and blood-pressure. Lancet 1:185-187 (Jan. 23) 1954. 7. Ferguson, F. C., Jr.: Drugs in hypertension. In Drill, V. A.: Pharmacology in Medicine: A Collaborative Textbook. New York, McGraw-Hill Book Company, Inc., 1954, pp. 34-1 to 34-12. 8. French, T. R.: The upright position in ether operations upon the nose, throat and other portions of the head. New York M. J. 95:1125-1130 (June 1) 1912. 9. Gardner, W. J.: The control of bleeding during operation by induced hypotension. J.A.M.A. 132:572-574 (Nov. 9) 1946. 10. Griffiths, H. W. C., and Gillies, John: Thoraco-lumbar splanchnicectomy and sympathectomy: Anaesthetic procedure. Anaesthesia 3:134-146, 1948. 11. Guyton, A. C.: Textbook of Medical Physiology. Philadelphia, W. B. Saunders Company, 1956, 1030 pp. 12. Gwathmey, J. T.: Anesthesia. New York, D. Appleton-Century Company, Inc., 1914, pp. 56-99. 13. Harris, H. E., and Hale, D. E.: Induced hypotension in the control of bleeding during fenestration operation. Cleveland Clin. Quart. 14:159-162 (July) 1947. 14. Little, D. M., Jr.: "Controlled Hypotension" in Anesthesia and Surgery. Springfield, Illinois, Charles C Thomas, Publisher, 1956, 159 pp. 15. Moersch, R. N., Patrick, R. T., and Clagett, O. T.: The use of hypotensive anesthesia in radical mastectomy. Ann. Surg. 152:911-918 (Nov.) 1960.
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P.
DIDIER, RICHARD
A.
THEYE
16. Morris, G. C., Jr., Moyer, J. H., Snyder, H. B., and Haynes, B. W., Jr.: Vascular dynamics in controlled hypotension: A study of cerebral and renal hemodynamics and blood volume changes. Ann. Surg. 138:706-711 (Nov.) 1953. 17. Morton, A. W.: Excision of the superior maxillary under medullary narcosis. Am. Med.5:451 (March 21) 1903. 18. Moyer, J. H., and Morris, George: Cerebral hemodynamics during controlled hypotension induced by the continuous infusion of ganglionic blocking agents (hexamethonium, pendiomide and Arfonad). J. Clin. Invest. 33:1081-1088, 1954. 19. Neily, H. H.: Physiological changes with induced hypotension, present status of clinical use. Canad. Anaesth. Soc. J. 10:244-258 (May) 1963. 20. Randall, L. 0., Peterson, W. G., and Lahmann, G.: The ganglionic blocking action ofthiophanium derivatives. J. Pharmacol. & Exper. Therap. 97:48-57 (Sept.) 1949. 21. Schalleck, William and Walz, Donald: Effects of drug-induced hypotension on the electro-encephalogram of the dog. Anesthesiology 15:673-680 (Nov.) 1954. 22. Smith, D. L., Didier, E. P., and Clagett, O. T.: Experience with controlled hypotension in radical mastectomy. (Unpublished data.) 23. Theye, R. A., and Tuohy, G. F.: Effect of trimetaphan haemodynamics and oxygen consumption during halothane anaesthesia in man. Brit. J. Anaesth. 37:144-151 (March) 1965. 24. Tuohy, G. F., and Theye, R. A.: Effects of Arfonad during ether anesthesia in man. Anesth. & Analg. 44:160-166 (March-April) 1965. 25. Van Bergen, F. H., Buckley, J. J., French, L. A., Dobkin, A. B., and Brown, 1. A.: Physiologic alterations associated with hexamethonium-induced hypotension. Anesthesiology 15:507-536 (Sept.) 1954.
HISTORY
Over the past 100 years or so, bleeding by leech or lancet has been replaced by an active concern for prevention of blood loss. This change in attitude is based in large part on greater awareness of the relationship between unreplaced blood loss and morbidity. In the past, blood loss during surgery was minimized through the use of the ligature, the pack, the hemostat, and the tourniquet, complemented of course by various drugs, astringents, and electrical devices. Among the more recent methods is controlled or induced hypotension, wherein the objective is to produce a relatively bloodless field or to reduce the effusion of blood by deliberately reducing the hydrostatic pressure in the vessels at the operative site. Gardner is credited with the first direct approach to the problem. In this approach a state of deliberate hemorrhagic shock was induced by arteriotomy and blood removal during the critical period of surgical excision of an intracranial lesion. Mter removal of the lesion, blood volume and pressure were restored to normal by reinfusion of the blood previously removed. In 1948, Griffiths and Gillies reported a method of reducing blood pressure by total subarachnoid block, and Bromage, in 1951, reported on hypotension produced by epidural anesthesia. At about the same time the use of various ganglionic blocking drugs2 , 5, 20 was becoming popular for the production of hypotension, and the advantage of controllability was emphasized. During this period Enderby 5, 6 pointed out the importance of gravitational effects, both good and bad, and suggested means of using them to advantage. These developments, although appearing to be new, were preceded by earlier references to the benefits and hazards of various anesthetic techniques and maneuvers which minimized bleeding and thereby provided more optimal surgical conditions. In fact, many of these earlier suggestions 1003
1004
EDWARD
F.
DAW, EDWARD
P.
DIDIER, RICHARD
A.
THEYE
are now considered important basic considerations in successful application of controlled hypotension. French, in 1912, discussed the advantages of his chair table in tonsillectomy under ether anesthesia and stated as follows: "There is less shock, and less disturbance in other ways, to the patient after operation because less ether is required to maintain narcosis when the sitting posture has been attained. This is, no doubt, due to the diminished blood pressure in the vessels of the head when the body is in the upright position and under the influence of a general anesthetic." Similarly, Morton, in 1903, reported a case of resection of the maxilla under cocaine spinal anesthesia, and he commented on the lack of shock in the awake patient and the excellence of the surgical field. Many other early clinicians were aware of some of the factors now considered as part of the technique of controlled hypotension, such as selection of chloroform versus ether, deep versus light anesthesia, position, and hyperventilation. 12 Despite this background, acceptance of the technique of controlled hypotension was limited and was viewed generally as a physiologic trespass until the introduction of the ganglionic blocking agents. With these drugs it became possible to reduce arterial pressure without the morbidity and hazard of hemorrhagic shock by arteriotomy and to avoid the technical problems and physiologic alterations of high spinal anesthesia. The drugs used for this purpose include pentamethonium, hexamethonium, trimethaphan camphorsulfonate, and sodium nitroprusside; this listing is approximately in the order of decreasing duration of activity and chronology of introduction of these agents.
METHODS OF PRODUCING HYPOTENSION
Three methods of reducing arterial blood pressure have been used: nonreplacement of blood and fluids, deliberate depression of the circulatory system by overdosage of anesthetic agent, and ganglionic or adrenergic blockade. All have in common the goal of diminished arterial bleeding in order to miniInize blood loss or to maintain visibility of the surgical field.
Nonreplacement of Blood and Fluids Arterial pressure may be lowered to hypotensive ranges by limiting replacement of blood and fluids during a period of massive blood loss. The reduction of arterial pressure, and thereby of volume of bleeding, may provide sufficient surgical exposure and time for the surgeon to gain control of the bleeding vessel. This technique, like arteriotomy, must be considered as essentially one of hemorrhagic and hypovolemic shock19 and is justified only in certain desperate surgical situations in which other approaches are deemed unsuitable.
Anesthetic Circulatory Depression Administration of increased concentrations of a potent anesthetic
CONTROLLED HYPOTENSION
1005
agent results in a lowering of blood pressure both by peripheral vasodilatation and by direct myocardial depression and subsequent reduction in cardiac output. This technique may safely be imposed only for short periods of moderate levels of hypotension, since the danger of severe depression and circulatory arrest is ever present. Halothane is probably the most convenient agent to use for this maneuver, because of its extreme potency, rapid onset of action and profound depression of the cardiovascular system. In addition, the administration of halothane is not associated with increased sympathetic nervous system activity or release of increased amounts of epinephrine and norepinephrine.
Ganglionic or Adrenergic Blockade Ganglionic or adrenergic blocking results in a lowering of arterial blood pressure when the reduction in peripheral resistance is achieved without a concomitant increase in cardiac output. This effect was accomplished in the past by blocking the sympathetic outflow by total subarachnoid or epidural block. The modern approach is to employ blocking agents. The drugs most often used are trimethaphan and hexamethonium. Other drugs which have been used include sodium nitroprusside, pentamethonium, tetraethyl ammonium, homatropinium, and pentolinium. 1. Trimethaphan (Arfonad) is the ganglionic blocking agent most commonly used in this country. The ease of inducing and controlling the degree of hypotension by means of an intravenous drip makes trimethaphan more suitable than a single-injection drug. Trimethaphan is usually administered as a 0.1 or 0.2 per cent solution; the speed of infusion determines the rate of the developing hypotension and the ultimate hypotensive level. Trimethaphan produces its action partly through competition with acetylcholine at the cholinergic receptor in the ganglion. The rapid and transient action of trimethaphan is due to its partial destruction by the enzyme cholinesterase. Some part of the hypotension produced may be due to histamine release. Circulatory compensatory mechanisms in patients receiving trimethaphan are greatly depressed; thus, any change in position should be accomplished before and not after the induction of hypotension. The hypotension produced with trimethaphan may be quickly reversed by the injection of a peripherally acting vasopressor. Along with the arterial hypotension there is often an increase in the heart rate. Provided that other circulatory depressant agents are absent, cardiac output may be affected little and peripheral resistance may be lowered. Pupillary dilatation occurs, presumably because the tonic parasympathetic function of the ciliary ganglion is blocked by the drug. The pupillary light reflex is abolished or diminished, as is accommodation of the pupil to near vision. The pupillary disturbance can interfere with the neurologic assessment of the patient postoperatively and it may be of concern to the patient, because of difficulty of vision due to the persistent pupillary dilatation. 2. Nearly all of the drugs of the methonium group have some gangli-
1006
EDWARD
F.
DAW, EDWARD
P.
DIDIER, RICHARD
A.
THEYE
onic blocking properties. It is characteristic of this group that as the straight chain of the drug increases in length, the ganglionic blocking properties become less pronounced and the drugs begin to assume curarelike properties. Thus, decamethonium (C-IO) is used clinically as a skeletal muscle relaxant and displays little evidence of ganglionic blocking properties. Hexamethonium (C-6), a quaternary ammonium compound, presumably produces hypotension through competition with acetylcholine at the ganglion site. The dosage varies according to the requirement of each patient and the degree of hypotension desired. Usually a small dose of 5 to 10 mg. is administered, and the individual response is noted; if no unusual response occurs, 25 to 50 mg. may be injected at the time hypotension is desired. Rarely, profound levels of hypotension may develop after the injection of the initial test dose of 5 to 10 mg. The response of the patient to the injected dose of hexamethonium may be varied by a change of position and by small reductions of blood volume. The hypotensive state may last 45 to 60 minutes. The level of the hypotension induced by hexamethonium can be modified by small repeated injections of a peripherally acting vasopressor. The hypotension-producing properties of tetraethyl ammonium (TEA; Etamon) have been known since 1914. The drug presumably acts by blocking the nicotinic action of acetylcholine. l1 Tetraethyl ammonium is usually injected intravenously in doses of 200 to 400 mg. Because of its prolonged action, this drug has very little use in clinical anesthesia. Pentamethonium (C-5) is another of this general methonium group and has been successfully used for the induction of hypotension. The uses and characteristics of the drug are similar to those of hexamethonium. 3. Sodium nitroprusside has been used clinically. Intravenous administration produces a rapid fall in blood pressure, presumably by the direct dilating action of the drug on the vessel wall. The hypotension is of such short duration that continuous infusion may be required. 7
PHYSIOLOGIC CONSIDERATIONS WITH INDUCED HYPOTENSION
As with any technique used to alter physiologic function, the advantages to the surgeon and the potential hazards to the patient must be considered together. In addition, not only the degree but also the duration of the period of induced hypotension must be taken into account. Low levels of perfusion pressure may not be tolerated well for even short periods of time, while moderate levels of perfusion may be tolerated for longer periods of time. Moyer and Morris presented evidence of decreased cerebral oxygen uptake during episodes of hypotension induced with hexamethonium. These reductions of cerebral oxygen uptake were coincidental with a decrease in cerebrovascular resistance. They found that as cerebral blood flow and
CONTROLLED HYPOTENSION
1007
oxygen uptake in the brain decreased there was an mcrease in the cerebral arterial-venous oxygen difference and a decrease in cerebral oxygen consumption. With the reversal of the hypotensive state by means of vasopressors, arterial blood pressure, cerebral blood flow, cerebral vascular resistance, and cerebral oxygen consumption all increased. With these changes in vascular dynamics, there was no change in cerebral metabolites indicative of hypoxic episodes. Van Bergen and associates noted a decrease in the voltage and fast activity on the electroencephalogram as the blood pressure fell. At arterial blood pressures of 50 mm. Hg and below, no surface electrical activity was obtained. The administration of vasopressors resulted in a return of electrical activity coincidental with the elevation of the arterial pressure. The appearance of an abnormal electroencephalographic pattern appears to be dependent on the speed of induction and on the degree of the hypotension. 21 Regardless of the level of hypotension produced by drugs, if the electroencephalogram should begin to show abnormal patterns-that is, high-voltage slow activity (delta waves)-or if periods of electrical inactivity develop, the hypotensive state should be reversed. Since the perfusion rate of the myocardium via the coronary arteries is directly related to the arterial diastolic pressure, there is a danger of myocardial ischemia as pressure is reduced. Electrocardiographic monitoring during the hypotensive state is therefore essential, particularly in patients with a history of myocardial or coronary insufficiency (or both). Changes in the rhythm and in the T-wave configuration and ST segment are helpful in detecting myocardial ischemia. In the same manner, any reduction in the hepatic artery perfusion pressure may compromise oxygenation of hepatic tissue. Hepatic blood flow may be reduced as much as 33 per cent during periods of induced hypotension. There have been reports of altered hepatic function and even hepatic failure after halothane anesthesia during which hypotensive episodes occurred. The effects of induced hypotension on the kidneys is difficult to assess. As arterial pressure is reduced, renal filtration decreases. All effective renal filtration may cease at levels of 70 mID. Hg. Even though renal filtration ceases, there is evidence that the decrease in vascular resistance as a result of the hypotension allows renal blood flow to be little affected. 16 Although the effects of lowered arterial blood pressure on only the brain, heart, liver, and kidney have been considered, it is to be remembered that physiologic function of all tissues and organs, and of the body as a whole, may be altered during induced hypotension. 19 In this regard, recent hemodynamic and metabolic studies during induced hypotension at the Mayo Clinic are of interest. 23 • 24 These observations were made in unpremedicated, paralyzed, supine patients artificially ventilated during varicose vein surgery with ether (five patients) or halothane (six patients) anesthesia. Two sets of observations were made before, during, and after 30 minutes of arterial hypotension induced with controlled amounts of trimethaphan given intravenously. The results are summarized in Table 1.
Table 1.
O.
PRESSURE, MEAN
(mm. Hg) CARDIAC OUTPUT
Arterial
With halothane anesthesia Before During
Arfonad
After With ether anesthesia Before
I r
Admd During After
,... = ~
Hemodynamics and Metabolism Before, During, and After Use of Arfonad with Halothane and with Ether Anesthesia: Average (and Range)
Right atrial
(L./min./m. 2)
HEART RATE, BEATS/ MIN.
STROKE
O.
VOLUME
UPTAKE
(ml./beat/m. 2) (ml./min./m. 2 )
SATURATION
(per cent)
SYSTEMIC RESISTANCE
Mixed venous
Right atrial observed
(dynes sec. cm. -5) trJ
I:j
~ 87 (72-101)
8 (4-12)
2.6 (2.2-3.1)
84 (78-90)
32 (26-36)
59 (47-71)
7 (5-9)
2.4 (2.0-2.9)
86 (80-93)
28 (23-32)
80 (66-99)
9 (5-12)
2.5 (2.0-2.9)
73 (65-84)
35 (27-41)
105 (81-123)
79 (77-82)
76 (72-77)
1390 (980-1850)
96 (76-115)
78 (74-79)
72 (66-78)
1000 (770-1250)
103 (83-120)
78 (73-81)
74 (70-75)
1290 (900-1440)
~
tJ
~~
trJ I:j
~
~
tJ
8
87 (66-117)
10 (6-12)
2.9 (2.3-3.5)
77 (60-102)
38 (34-42)
116 (110-120)
80 (75-85)
78 (72-85)
1140 (840-1390)
60 (52-71)
9 (5-12)
2.7 (2.3-3.5)
84 (68-117)
32 (30-35)
108 (101-113)
80 (73-84)
74 (67-86)
800 (570-990)
o
95 (77-120)
9 (5-11)
3.4 (3.1-3.8)
82 (69-109)
40 (35-43)
114 (109-119)
83 (79-85)
80 (78-83)
1190 (1020-1390)
?--
[;j
JtI ~
~
~
(Reproduced with permission from Tuohy, G. F. and Theye, R. A.: Effect of trimetaphan and haemodynamics and oxygen consumption during halothane anaesthesia in man. Brit. J. Anaesth. 37:144-151 [March] 1965.)
~
~
CONTROLLED HYPOTENSION
1009
It is apparent that trimethaphan was effective in inducing a similar degree of hypotension with either halothane or ether. The hemodynamic recovery, however, was more vigorous during anesthesia with ether than with halothane. The lowering of arterial pressure was achieved primarily by reduction in peripheral vascular resistance. Changes in cardiac output with trimethaphan were small, not entirely consistent, and probably functionally insignificant. Since stroke volume always fell significantly with trimethaphan, it follows that an increasing heart rate serves an important role in maintaining cardiac output during administration of trimethaphan. Oxygen uptake fell with induced hypotension. The changes in cardiac output and oxygen uptake were similar in degree and direction so that mixed venous oxygen levels were not changed significantly. Thus, over-all, no profound or significant alterations in the whole-body oxygen transport system were found to occur with induced hypotension in these studies.
CLINICAL APPLICATION
Ditzler's recent survey of leading American medical institutions suggests that the primary indication for use of induced hypotension presently is the facilitation of surgery. Earlier, Ditzler and Eckenhoff had observed that in the two types of operations investigated there was a significant conservation of blood (20 to 35 per cent) but an increase in the duration of the operation. At the Mayo Clinic the experience with controlled hypotension during radical mastectomyl5. 22 suggests that facilitation of surgery is a suitable indication for the use of a safe technique for hypotension, that increased morbidity and mortality associated with controlled hypotension arise from errors in technique or from improper selection of patients, and that, in a general sense, those factors that are advantageous to the surgeon are of benefit to the patient. Thus, in practice, the use of controlled hypotension is indicated primarily by considerations of facilitating operations, minimizing blood loss during operation, or permitting operations not otherwise possible.1 3 Accordingly, induced hypotension may be of value in the operative treatment of intracranial aneurysms and large vascular intracranial tumors, certain cardiovascular procedures, radical head and neck surgery, the fenestration operation,14 and radical mastectomy.
PRECAUTIONS AND CONSIDERATIONS IN THE USE OF INDUCED HYPOTENSION
There are probably many relative and few absolute contraindications to the use of induced hypotension. If a major surgical procedure is deemed
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necessary in the presence of myocardial, renal, or hepatic disease, and if indications for the use of induced hypotension exist, these techniques can probably be used. The amount of reduction should not be arbitrary but rather should be tailored to meet the needs of the operation without undue hazard to the patient. In many patients, reduction of arterial pressure to 90 to 100 mm. Hg may be just as effective in reducing the degree and force of blood loss as reduction to 60 to 70 rom. Hg. Patients in whom hypotensive techniques are to be used should be monitored by the electrocardiogram and probably the electroencephalogram, as previously discussed, and by central venous and intra-arterial blood pressure recording if these techniques are available. The pattern of change in central venous pressure may serve as a guide to fluid volume replacement. During techniques of hypotension, with the blood pressure maintained by constant infusion of ganglionic blocking agents, guides to blood replacement therapy may be inadequate or absent. A rising or falling venous pressure, in the presence of unchanged myocardial function, usually is indicative of the status of fluid and blood replacement. Certain precautions should be observed when hypotension is induced with ganglionic blocking agents. A vasopressor should be instantly available for use in reversal of the hypotension. Rates of infusion should be controlled precisely, and the infusion line, when not needed, should be disconnected from the infusion needle or should be secured with a metal clamp. Mter termination of the hypotensive period, the infusion set should be discarded. The position of the patient should remain stable, although minor variations of position may be used to alter the level of arterial pressure. It should be remembered that the blood pressure recorded at the site of an arterial needle or arm cuff may be considerably higher than that at the level of the cerebral circulation. Enderby 6 found that for every inch the head is elevated above the level of the heart, the cerebral perfusion pressure is reduced 2 rom. Hg in relation to the pressure at heart level. A critical level of pressure that maintains capillary perfusion has been determined to be 32 mm. Hg. In addition, blood flow to critical areas such as the head may be reduced because of the elastic quality of small vessels and local tissue compression due to tumor mass, hemorrhage, or retraction. Because external pressure may increase the critical opening pressure of the arterioles, levels of induced hypotension must not be as low as usual in the presence of increased intracranial pressure. Some prefer to use moderate surface hypothermia (32 0 to 300 C.) in conjunction with induced hypotension in order to offer some protection against the reduced tissue perfusion that prevails during hypotension.
SUMMARY
The use of controlled hypotension may be indicated for some surgical
1011
CONTROLLED HYPOTENSION
procedures, which include intracranial and cardiovascular operations, radical head and neck surgery, radical mastectomy, and fenestration procedures. Morbidity and mortality attributed to controlled hypotension has been the result of improper and injudicious use. When this technique is used properly, overall morbidity and mortality could be less for these procedures than that expected if the advantages of controlled hypotension were not obtained. In this institution trimethaphan (Arfonad) is the drug of choice for controlled hypotension. The rapidity and short duration of action of trimethaphan produce an easily controlled level of arterial hypotension. As arterial hypotension is produced, tissue perfusion must diminish. The levels of arterial hypotension should be equated with time to assess possible compromise of the cerebral, hepatic, renal, and coronary blood flows. Because controlled hypotension, properly applied, offers definite advantages to the surgical procedure and is to the benefit of the patient, this technique has a definite place in anesthesia-surgical practice.
REFERENCES 1. Bromage, P. R.: Vascular hypotension in 107 cases of epidural analgesia. Anaesthesia 6:26-29 (Jan.) 1951. 2. Davison, M. H. A.: Pentamethonium iodide in anaesthesia. Lancet 1 :252-253 (Feb. 11) 1950. 3. Ditzler, J. W.: Current status of deliberately induced hypotension. Anesth. & Analg. 43:116-120 (Jan.-Feb.) 1964. 4. Ditzler, J. W., and Eckenhoff, J. E.: Comparison of blood loss and operative time in certain surgical procedures completed with and without controlled hypotension. Ann. Surg. 143:289-293 (March) 1956. 5. Enderby, G. E. H.: Controlled circulation with hypotensive drugs and posture to reduce bleeding in surgery: Preliminary results with pentamethonium iodide. Lancet 1:1145-1147 (June 24) 1950. 6. Enderby, G. E. H.: Postural ischaemia and blood-pressure. Lancet 1:185-187 (Jan. 23) 1954. 7. Ferguson, F. C., Jr.: Drugs in hypertension. In Drill, V. A.: Pharmacology in Medicine: A Collaborative Textbook. New York, McGraw-Hill Book Company, Inc., 1954, pp. 34-1 to 34-12. 8. French, T. R.: The upright position in ether operations upon the nose, throat and other portions of the head. New York M. J. 95:1125-1130 (June 1) 1912. 9. Gardner, W. J.: The control of bleeding during operation by induced hypotension. J.A.M.A. 132:572-574 (Nov. 9) 1946. 10. Griffiths, H. W. C., and Gillies, John: Thoraco-lumbar splanchnicectomy and sympathectomy: Anaesthetic procedure. Anaesthesia 3:134-146, 1948. 11. Guyton, A. C.: Textbook of Medical Physiology. Philadelphia, W. B. Saunders Company, 1956, 1030 pp. 12. Gwathmey, J. T.: Anesthesia. New York, D. Appleton-Century Company, Inc., 1914, pp. 56-99. 13. Harris, H. E., and Hale, D. E.: Induced hypotension in the control of bleeding during fenestration operation. Cleveland Clin. Quart. 14:159-162 (July) 1947. 14. Little, D. M., Jr.: "Controlled Hypotension" in Anesthesia and Surgery. Springfield, Illinois, Charles C Thomas, Publisher, 1956, 159 pp. 15. Moersch, R. N., Patrick, R. T., and Clagett, O. T.: The use of hypotensive anesthesia in radical mastectomy. Ann. Surg. 152:911-918 (Nov.) 1960.
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16. Morris, G. C., Jr., Moyer, J. H., Snyder, H. B., and Haynes, B. W., Jr.: Vascular dynamics in controlled hypotension: A study of cerebral and renal hemodynamics and blood volume changes. Ann. Surg. 138:706-711 (Nov.) 1953. 17. Morton, A. W.: Excision of the superior maxillary under medullary narcosis. Am. Med.5:451 (March 21) 1903. 18. Moyer, J. H., and Morris, George: Cerebral hemodynamics during controlled hypotension induced by the continuous infusion of ganglionic blocking agents (hexamethonium, pendiomide and Arfonad). J. Clin. Invest. 33:1081-1088, 1954. 19. Neily, H. H.: Physiological changes with induced hypotension, present status of clinical use. Canad. Anaesth. Soc. J. 10:244-258 (May) 1963. 20. Randall, L. 0., Peterson, W. G., and Lahmann, G.: The ganglionic blocking action ofthiophanium derivatives. J. Pharmacol. & Exper. Therap. 97:48-57 (Sept.) 1949. 21. Schalleck, William and Walz, Donald: Effects of drug-induced hypotension on the electro-encephalogram of the dog. Anesthesiology 15:673-680 (Nov.) 1954. 22. Smith, D. L., Didier, E. P., and Clagett, O. T.: Experience with controlled hypotension in radical mastectomy. (Unpublished data.) 23. Theye, R. A., and Tuohy, G. F.: Effect of trimetaphan haemodynamics and oxygen consumption during halothane anaesthesia in man. Brit. J. Anaesth. 37:144-151 (March) 1965. 24. Tuohy, G. F., and Theye, R. A.: Effects of Arfonad during ether anesthesia in man. Anesth. & Analg. 44:160-166 (March-April) 1965. 25. Van Bergen, F. H., Buckley, J. J., French, L. A., Dobkin, A. B., and Brown, 1. A.: Physiologic alterations associated with hexamethonium-induced hypotension. Anesthesiology 15:507-536 (Sept.) 1954.