Current Medical Research and Opinion
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: http://www.tandfonline.com/loi/icmo20
The use of indoramin to induce hypotension during general anaesthesia N. J. Paymaster MB., B.S., F.F.A.R.C.S.(Eng.) To cite this article: N. J. Paymaster MB., B.S., F.F.A.R.C.S.(Eng.) (1975) The use of indoramin to induce hypotension during general anaesthesia, Current Medical Research and Opinion, 3:1, 39-42, DOI: 10.1185/03007997509113644 To link to this article: http://dx.doi.org/10.1185/03007997509113644
Published online: 05 Aug 2008.
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Date: 05 November 2015, At: 15:44
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Current Medical Research and Opinion
Vol. 3, No. 1 , 1975
The use of indoramin to induce hypotension during general anaesthesia
F.F.A. R.C.S.(Eng.)
Cur. med. Res. Opin., (1975), 3, 39.
N. J. Paymaster,* M.B., B.S., Clatterbridge Hospital, Bebingfon, Wirral, England
Received: 25th November 1974
Summary The a-blocker indoramin had only modest hypotensive action in the normotensive, anaesthetised, paralysed patient undergoing major surgical intervention but had a greater effect in the hypertensive patient. The absence of deleterious cardiac eflects even with intravenous doses as high as I mg./kg. supports previous$ndings as to the safety of this compound. It is possible that indoramin potentiates the hypotensive action of halothane but there is no evidence to suggest that an adverse interaction might arise when halothane is used to anaesthetise a patient receiving indoramin treatment. Key words: Indoramin - halothane - anaesthesia, general
Introduction Indoramin is an a-adrenoceptor blocker3e7 with cardioinhibitory as well as vasodilator actions. It has been shown to lower blood pressure in all animal species so far studied' whether conscious or anaesthetised, normotensive or hypertensive and by both oral and parenteral routes of administration. Several investigators have established the hypotensive action of indoramin in patients with essential hyperten~ion.~,6,* The purpose of the present study was to investigate the effects of indoramin as a hypotensive adjunct to anaesthesia in operations associated with profuse blood loss. r 2
Methods Ten patients who underwent major surgery under general anaesthesia were studied. Before the operation, suitability for hypotensive anaesthesia was determined by undertaking a routine history, physical examination, an X-ray of the chest, an electrocardiogram, haematological and biochemical investigations. Prernedication consisted of 2 mg. lorazepam (6 patients) or 10 mg. diazepam (4 patients) given orally the night before and 2 hours before surgery. Pulse and arterial blood pressure measurements and a n electrocardiogram recording were made before general anaesthesia was induced with intravenous thiopentone sodium 'Consultant Anaesthetist 39
Downloaded by [University of California Santa Barbara] at 15:44 05 November 2015
The use of indoramin to induce hypotension during general anaesthesia
(mean dose 280 mg.). Next, the non-depolarising muscle relaxant alcuronium (mean dose 16.8 mg.) was given intravenously and ventilation was maintained using a mechanical ventilator. Intratracheal nitrous oxide and oxygen were administered via a semi-closed system incorporating a carbon dioxide absorber. Indoramin was injected intravenously (mean dose 26 mg.) initially between 10 and 20 minutes after induction of anaesthesia and supplementary amounts used as required. Heart rate and E.C.G. were monitored continuously and arterial blood pressure was measured at 5 to 15 minute intervals throughout anaesthesia. Fluids including blood were infused intravenously as required and blood loss measured gravimetrically. Six of the 10 patients, after they had received their total indoramin dose, were given halothane in addition to nitrous oxide and oxygen. On recovery from anaesthesia, the patients were observed carefully and arterial blood pressure and pulse rate were monitored every 15 minutes for 2 hours and thereafter every 30 minutes for 6 hours.
Results The characteristics of the patients, their operations, premedicants, indoramin dosage and blood loss are presented in Table I. The total dosage of indoramin varied from 10 to 110 mg. (0.13 to 1.02 mg./kg.), the mean being 46.25 59.15 mg. Table I. Patient characteristics Patient Initial No.
Sex
Age
Operation
Premedication
Total dose of indoramin
Halothane
Blood loss
1
F.A.
M
56
Prostatectomy
Lorazepam
50 (0.69 mg./kg.)
-t
200 ml.
2
B.
M
60
Prostatectomy
Lorazepam
so
+
250 ml.
(0.72 mg./kg.) 3
E.B.
M
58
Nephrectomy
Diazepam
10 (0.15 mg./kg.)
-
320 ml.
4
A.B.
F
50
Simple mastectomy
Diazepam
10.5 (0.13 rng./kg.)
-
581 ml.
5
M.B.
F
44
Lumbo-sacral spinal fusion
Diazepam
26 (0.41 mg./kg.)
+
96 ml.
F.C.
M
53
McKee-Farrar arthroplasty
Lorazepam
-t-
loo0 ml.
6 ~
~~
~~
~
~
110
(1.02 mg./kg.) ~
7
J.E.
M
57
Laminectomy
Diazepam
38 (0.50 mg./kg.)
-I
198 ml.
8
S.F.
M
59
Bladderneck resection
Lorazepam
60 (0.81 mg./kg.)
-
400 ml.
9
V.H.
F
72
McKee-Farrar artbroplasty
Lorazepam
60 (0.79 nig./kg.)
-t
700 ml.
10
R.S.
M
68
Bladderneck resection
Lorazepam
48 (0.75 mg./kg.)
-
220 ml.
The mean arterial blood pressure following premedication, curarisation and intubation was 153.0/87.8 mm.Hg. After indoramin, but before the administration 40
Downloaded by [University of California Santa Barbara] at 15:44 05 November 2015
N. J. Paymaster
of halothane, the arterial blood pressure was 136.4p0.5 mm.Hg. This hypotensive effect was frequently interrupted by a rise in blood pressure associated with the first incision. It was noted that in the 2 patients who had a high initial arterial blood pressure, this was reduced from 165/95 to 125/75 mm.Hg. after indoramin. The arterial blood pressure decreased rapidly (to a mean level of 84.2/59.2 mm.Hg.) when halothane was administered to 6 patients who had received indoramin. This decrease in pressure was quickly reversed when halothane administration was discontinued. The clinical impression was that this fall in arterial blood pressure was potentiated by the a-blocker and typical examples of this effect are presented in Figure I . Figure 1. Blood pressures and heart rates of 2 patients following induction of anaesthesia by thiopentone sodium hticnt
R.
Patient J.E
u
5 200
n
L
200
::/-yJ&
r.
150 E E v
e e
2
sm
so
100
‘0
so J.
I 0
4
4
Int.
Inc.
Ib
t t O;
34.5
15.5
3;
40 1nJor:iniiii
O;
QO mins. 8 4 4 6
R
8 nig. Indoraniin
The points of intubation (Int.) and incision (Inc.) are noted. Halothane was administered for the period shown by the hatched horizontal bar (H). Note the marked hypotensive response. Patient B. received 50 mg. indoramin in 2 doses and Patient J.E. received 38 mg. indoramin divided into 6 doses, as shown.
Heart rate was not affected by indoramin, nor was the E.C.G. which showed a sinus rhythm throughout anaesthesia in all patients. Only 2 patients required blood as a result of the operation, and the remainder had either 0.9 % saline or 5 % dextrose. The contribution of these intravenous infusions to the effect of indoramin on arterial blood pressure remains unknown. The administration of indoramin had no effect on the rate at which consciousness was regained and all patients had uneventful post-operative courses. 41
The use of indoramin to induce hypotension during general anaesthesia
Downloaded by [University of California Santa Barbara] at 15:44 05 November 2015
Discussion The intravenous administration of indoramin to 10 anaesthetised patients produced a fall in arterial blood pressure which was most marked in 2 patients known to be hypertensive. The results presented here would suggest that it is not particularly suitable to produce intense hypotension during anaesthesia unless combined with the use of halothace. It must be pointed out that the intense hypotension, rapidly achieved to minimise blood loss during surgery, is neither aimed for, nor desirable, in the therapeutic management of essential hypertension in the conscious ambulant patient. The hypotensive action of indoramin in patients with essential hypertension has been adequately established by several investigators. The small hypotensive effect of indoramin in the normotensive patient has two important consequences. First, the drug is safe when administered with a general anaesthetic provided that a possible potentiating effect with halothane is borne in mind. This will be of importance when hypertensive patients controlled on the drug present for surgery. Second, it would appear that vasodilatation by cr-blockade in an otherwise normotensive individual as described by Fares and Milliken4 might be brought about without symptomatic hypotensive episodes. The absence of any undesirable actions of indoramin even in the large doses used deserves special mention and confirms the findings of other investigators.
References I . Alps, B. J., Borrows, E. T., Johnson, E. S., Staniforth, M. W., and Wilson, A. B., (1972). A comparison of the cardiovascular actions of indoramin, propranolol, lignocaine and quinidine. Cardiovascular Res., 6, 226-234. 2. Baum, T., Shropshire, A. T., Eckfeld, D. K., Metz, N., Dinish, J. L., Peters, J. R., Butz, F., and Gluckman, M. I., (1973). Studies relating to the antihypertensive and antidysrhythmic action of indoramin. Arch. in?.Pharmacodyn., 204,380-406. 3. Collis, M. G . ,and Alps, B. J., (1973).The evaluation of the cc-adrenoceptorblocking action of indoramin, phentolamine and thymoxamine on the rat and guinea-pig isolated mesenteric vasculature and aortic spiral preparations. J. Pharm. Pharmac., 25,621 -628. 4. Fares, C. M., and Milliken, J. C., (1974). The effect of parenteral indoramin on peripheral blood flow in patients with Raynaud’s Disease or atherosclerosis associated with intermittent claudication. Curr. med. Res. Opin., 2, 57-62. 5. Kramer, R., Rosendorff, C., and Bloom, D., (1974). Clinical evaluation of indoramin as the sole agent for the treatment of hypertension. S. Afi. med.J., 48,1569-1572. 6. Lewis, P. J., George, C. F., and Dollery, C. T., (1973). Clinical evaluation of indoramin, a new antihypertensive agent. Ewop. J . Clin. Pharmacot., 6,211-216. 7. Variava, D. H., and Turner, P., (1973). The a-adrenoceptor blocking effect of indoramin on human isolated smooth muscle. J. Pharm. Pharmac., 23, 629-632. 8 . White, C. de B., Royds, R. B., and Turner, P., (1974). Some clinical pharmacological studies with indoramin with observations on its therapeutic usefulness. Postgrad. Med. J . (In press).
42
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: http://www.tandfonline.com/loi/icmo20
The use of indoramin to induce hypotension during general anaesthesia N. J. Paymaster MB., B.S., F.F.A.R.C.S.(Eng.) To cite this article: N. J. Paymaster MB., B.S., F.F.A.R.C.S.(Eng.) (1975) The use of indoramin to induce hypotension during general anaesthesia, Current Medical Research and Opinion, 3:1, 39-42, DOI: 10.1185/03007997509113644 To link to this article: http://dx.doi.org/10.1185/03007997509113644
Published online: 05 Aug 2008.
Submit your article to this journal
Article views: 2
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icmo20 Download by: [University of California Santa Barbara]
Date: 05 November 2015, At: 15:44
Downloaded by [University of California Santa Barbara] at 15:44 05 November 2015
Current Medical Research and Opinion
Vol. 3, No. 1 , 1975
The use of indoramin to induce hypotension during general anaesthesia
F.F.A. R.C.S.(Eng.)
Cur. med. Res. Opin., (1975), 3, 39.
N. J. Paymaster,* M.B., B.S., Clatterbridge Hospital, Bebingfon, Wirral, England
Received: 25th November 1974
Summary The a-blocker indoramin had only modest hypotensive action in the normotensive, anaesthetised, paralysed patient undergoing major surgical intervention but had a greater effect in the hypertensive patient. The absence of deleterious cardiac eflects even with intravenous doses as high as I mg./kg. supports previous$ndings as to the safety of this compound. It is possible that indoramin potentiates the hypotensive action of halothane but there is no evidence to suggest that an adverse interaction might arise when halothane is used to anaesthetise a patient receiving indoramin treatment. Key words: Indoramin - halothane - anaesthesia, general
Introduction Indoramin is an a-adrenoceptor blocker3e7 with cardioinhibitory as well as vasodilator actions. It has been shown to lower blood pressure in all animal species so far studied' whether conscious or anaesthetised, normotensive or hypertensive and by both oral and parenteral routes of administration. Several investigators have established the hypotensive action of indoramin in patients with essential hyperten~ion.~,6,* The purpose of the present study was to investigate the effects of indoramin as a hypotensive adjunct to anaesthesia in operations associated with profuse blood loss. r 2
Methods Ten patients who underwent major surgery under general anaesthesia were studied. Before the operation, suitability for hypotensive anaesthesia was determined by undertaking a routine history, physical examination, an X-ray of the chest, an electrocardiogram, haematological and biochemical investigations. Prernedication consisted of 2 mg. lorazepam (6 patients) or 10 mg. diazepam (4 patients) given orally the night before and 2 hours before surgery. Pulse and arterial blood pressure measurements and a n electrocardiogram recording were made before general anaesthesia was induced with intravenous thiopentone sodium 'Consultant Anaesthetist 39
Downloaded by [University of California Santa Barbara] at 15:44 05 November 2015
The use of indoramin to induce hypotension during general anaesthesia
(mean dose 280 mg.). Next, the non-depolarising muscle relaxant alcuronium (mean dose 16.8 mg.) was given intravenously and ventilation was maintained using a mechanical ventilator. Intratracheal nitrous oxide and oxygen were administered via a semi-closed system incorporating a carbon dioxide absorber. Indoramin was injected intravenously (mean dose 26 mg.) initially between 10 and 20 minutes after induction of anaesthesia and supplementary amounts used as required. Heart rate and E.C.G. were monitored continuously and arterial blood pressure was measured at 5 to 15 minute intervals throughout anaesthesia. Fluids including blood were infused intravenously as required and blood loss measured gravimetrically. Six of the 10 patients, after they had received their total indoramin dose, were given halothane in addition to nitrous oxide and oxygen. On recovery from anaesthesia, the patients were observed carefully and arterial blood pressure and pulse rate were monitored every 15 minutes for 2 hours and thereafter every 30 minutes for 6 hours.
Results The characteristics of the patients, their operations, premedicants, indoramin dosage and blood loss are presented in Table I. The total dosage of indoramin varied from 10 to 110 mg. (0.13 to 1.02 mg./kg.), the mean being 46.25 59.15 mg. Table I. Patient characteristics Patient Initial No.
Sex
Age
Operation
Premedication
Total dose of indoramin
Halothane
Blood loss
1
F.A.
M
56
Prostatectomy
Lorazepam
50 (0.69 mg./kg.)
-t
200 ml.
2
B.
M
60
Prostatectomy
Lorazepam
so
+
250 ml.
(0.72 mg./kg.) 3
E.B.
M
58
Nephrectomy
Diazepam
10 (0.15 mg./kg.)
-
320 ml.
4
A.B.
F
50
Simple mastectomy
Diazepam
10.5 (0.13 rng./kg.)
-
581 ml.
5
M.B.
F
44
Lumbo-sacral spinal fusion
Diazepam
26 (0.41 mg./kg.)
+
96 ml.
F.C.
M
53
McKee-Farrar arthroplasty
Lorazepam
-t-
loo0 ml.
6 ~
~~
~~
~
~
110
(1.02 mg./kg.) ~
7
J.E.
M
57
Laminectomy
Diazepam
38 (0.50 mg./kg.)
-I
198 ml.
8
S.F.
M
59
Bladderneck resection
Lorazepam
60 (0.81 mg./kg.)
-
400 ml.
9
V.H.
F
72
McKee-Farrar artbroplasty
Lorazepam
60 (0.79 nig./kg.)
-t
700 ml.
10
R.S.
M
68
Bladderneck resection
Lorazepam
48 (0.75 mg./kg.)
-
220 ml.
The mean arterial blood pressure following premedication, curarisation and intubation was 153.0/87.8 mm.Hg. After indoramin, but before the administration 40
Downloaded by [University of California Santa Barbara] at 15:44 05 November 2015
N. J. Paymaster
of halothane, the arterial blood pressure was 136.4p0.5 mm.Hg. This hypotensive effect was frequently interrupted by a rise in blood pressure associated with the first incision. It was noted that in the 2 patients who had a high initial arterial blood pressure, this was reduced from 165/95 to 125/75 mm.Hg. after indoramin. The arterial blood pressure decreased rapidly (to a mean level of 84.2/59.2 mm.Hg.) when halothane was administered to 6 patients who had received indoramin. This decrease in pressure was quickly reversed when halothane administration was discontinued. The clinical impression was that this fall in arterial blood pressure was potentiated by the a-blocker and typical examples of this effect are presented in Figure I . Figure 1. Blood pressures and heart rates of 2 patients following induction of anaesthesia by thiopentone sodium hticnt
R.
Patient J.E
u
5 200
n
L
200
::/-yJ&
r.
150 E E v
e e
2
sm
so
100
‘0
so J.
I 0
4
4
Int.
Inc.
Ib
t t O;
34.5
15.5
3;
40 1nJor:iniiii
O;
QO mins. 8 4 4 6
R
8 nig. Indoraniin
The points of intubation (Int.) and incision (Inc.) are noted. Halothane was administered for the period shown by the hatched horizontal bar (H). Note the marked hypotensive response. Patient B. received 50 mg. indoramin in 2 doses and Patient J.E. received 38 mg. indoramin divided into 6 doses, as shown.
Heart rate was not affected by indoramin, nor was the E.C.G. which showed a sinus rhythm throughout anaesthesia in all patients. Only 2 patients required blood as a result of the operation, and the remainder had either 0.9 % saline or 5 % dextrose. The contribution of these intravenous infusions to the effect of indoramin on arterial blood pressure remains unknown. The administration of indoramin had no effect on the rate at which consciousness was regained and all patients had uneventful post-operative courses. 41
The use of indoramin to induce hypotension during general anaesthesia
Downloaded by [University of California Santa Barbara] at 15:44 05 November 2015
Discussion The intravenous administration of indoramin to 10 anaesthetised patients produced a fall in arterial blood pressure which was most marked in 2 patients known to be hypertensive. The results presented here would suggest that it is not particularly suitable to produce intense hypotension during anaesthesia unless combined with the use of halothace. It must be pointed out that the intense hypotension, rapidly achieved to minimise blood loss during surgery, is neither aimed for, nor desirable, in the therapeutic management of essential hypertension in the conscious ambulant patient. The hypotensive action of indoramin in patients with essential hypertension has been adequately established by several investigators. The small hypotensive effect of indoramin in the normotensive patient has two important consequences. First, the drug is safe when administered with a general anaesthetic provided that a possible potentiating effect with halothane is borne in mind. This will be of importance when hypertensive patients controlled on the drug present for surgery. Second, it would appear that vasodilatation by cr-blockade in an otherwise normotensive individual as described by Fares and Milliken4 might be brought about without symptomatic hypotensive episodes. The absence of any undesirable actions of indoramin even in the large doses used deserves special mention and confirms the findings of other investigators.
References I . Alps, B. J., Borrows, E. T., Johnson, E. S., Staniforth, M. W., and Wilson, A. B., (1972). A comparison of the cardiovascular actions of indoramin, propranolol, lignocaine and quinidine. Cardiovascular Res., 6, 226-234. 2. Baum, T., Shropshire, A. T., Eckfeld, D. K., Metz, N., Dinish, J. L., Peters, J. R., Butz, F., and Gluckman, M. I., (1973). Studies relating to the antihypertensive and antidysrhythmic action of indoramin. Arch. in?.Pharmacodyn., 204,380-406. 3. Collis, M. G . ,and Alps, B. J., (1973).The evaluation of the cc-adrenoceptorblocking action of indoramin, phentolamine and thymoxamine on the rat and guinea-pig isolated mesenteric vasculature and aortic spiral preparations. J. Pharm. Pharmac., 25,621 -628. 4. Fares, C. M., and Milliken, J. C., (1974). The effect of parenteral indoramin on peripheral blood flow in patients with Raynaud’s Disease or atherosclerosis associated with intermittent claudication. Curr. med. Res. Opin., 2, 57-62. 5. Kramer, R., Rosendorff, C., and Bloom, D., (1974). Clinical evaluation of indoramin as the sole agent for the treatment of hypertension. S. Afi. med.J., 48,1569-1572. 6. Lewis, P. J., George, C. F., and Dollery, C. T., (1973). Clinical evaluation of indoramin, a new antihypertensive agent. Ewop. J . Clin. Pharmacot., 6,211-216. 7. Variava, D. H., and Turner, P., (1973). The a-adrenoceptor blocking effect of indoramin on human isolated smooth muscle. J. Pharm. Pharmac., 23, 629-632. 8 . White, C. de B., Royds, R. B., and Turner, P., (1974). Some clinical pharmacological studies with indoramin with observations on its therapeutic usefulness. Postgrad. Med. J . (In press).
42
