- Email: [email protected]
CURARE IN ANÆSTHESIA
75
curare it has been possible to perform operations such as a gastrectomy, using no other anaesthetic agent. This involves a revolutionary view of the physiological action of curare and is not easily explained, but from the purely clinical viewpoint it is reassuring to know that even such large doses of curare may be given without irreversible effect. During the recovery period Whitacre’s patients showed some tendency to bronchospasm,
,
increased bronchial secretion, and other undesirable side-effects, so that neither he nor I advocate using We are. just curare as a practical method of anaesthesia. glad to Bknow that doses up to 400 mg. have been given to human patients without fatal effect. An even more striking example of an overdose of curare has been reported by Robson of Toronto (1945). His patient. was an 8 lb. baby, two weeks old, undergoing operation for a complete diaphragmatic hernia under ether anaesthesia. By mistake a dose of 1 c.cm. of intocostrin (20 mg. curare) was given intravenously to improve relaxation. This was at least fifteen times the dose for such a patient. There was recommended immediate complete relaxation and also complete cessation of respiration. Dr. Robson cleverly maintained artificial respiration with endotracheal oxygen for more than three hours before there was the least sign of returning muscular activity. In the meantime, the surgeon hadcompleted the operation under ideal conditions, and eventually the baby recovered without permanent
damage.
relaxant in patients under cyclopropane, ether, and other general anaesthetic agents. In the light of more than three years’ clinical experience, curare is considered to be of value to expert an2esthetists by affording a better surgical field for abdominal operations with light and non-toxic anæsthesia. It will probably have a permanent place in anoesthesiology. REFERENCES
Baird, J. W., Adams, R. C. (1944) Proc. Mayo Clin. 19, 193. Bennett, A. E. (1940) J. Amer. med. Ass. 114, 322. Bernard, C. (1865) Bull. gén. Thérap. 69, 23. Cullen, S. E. (1943) Surgery, 14, 2 ; (1944) Anesthesiology, 5, 166. Gill, R. C. (1940) White Water and Black Magic, New York. Griffith, H. R., Johnson, G. E. (1942) Anesthesiology, 3, 418. Hudon, F. (1944) Laval méd. 9, 242. Knight, R. T. (1944) Minn. Med. 27, 667. Leech, B. C., Griffith, H. R. (1940) Canad. med. Ass. J. 42, 434. McIntyre, A. R., King. R. E. (1943) Science, 97, 69, 516. Robson, C. H. (1945) Read at Canadian Medical Association in Montreal.
Waters, R. M. (1944) Anesthesiology, 5, 618. Whitacre, R. J., Fisher, A. J. (1945) Ibid, 6, 124.
CURARE
IN
ANÆSTHESIA
F. BARNETT MALLINSON, M R C S, D A ANÆSTHETIST, PRINCESS BEATRICE, WOOLWICH MEMORIAL, AND ROYAL WATERLOO HOSPITALS; AND EATS
THE inception of curare in anaesthesia dates back to 1942 when Griffith and Johnson of Canada described hope they will not cause us to forget that when impro- their experiences in 25 cases. In 1943 Cullen published and clearly detailed observations on 1000 cases perly used curare is still a poison, capable of producing careful in the United States. The preparation of curare used death by respiratory paralysis. by these workers and employed in the present trial is The only side-effect which we have noted with curare, called ’Intocostrin’ and is manufactured by E. R. other than occasional respiratory depression, is a transiSquibb and Sons. The following observations are in which three developed patients intended ent bronchospasm as a preliminary report on a very promising after of the intravenous injection moderate immediately doses. This is recorded as a possible effect of curare, innovation. Intocostrin is a pure extract of curare, freed of alkawith no suggestion as to the cause-the patients resumed loids having toxic effects on heart and respiratory centre, normal breathing within one or two minutes. The assayed and standardised to contain 20 mg. preparations of curare we have used, intocostrin, and a biologically of the pure alkaloid per c.cm. (Baird and Adams 1944, new preparation D-tubocurarine,’ are not irritating to Cullen 1944). the subcutaneous tissues, and there has been no recorded Its purpose in anaesthesia, is to obtain maximum relaxacase of phlebitis or other similar complication. tion for abdominal surgery without the disadvantages ITS FUTURE of spinal or deep general anaesthesia. Curare neutraFive years ago when it was first suggested to me by Dr. lises the action of acetylcholine at the myoneural L. H. Wright, of New York, that curare might be useful junction thus acting only on voluntary muscle and in anaesthesia, I laughed at the ’idea. But I thought certain parasympathetic nerves (Cole 1945, - Griffith about it for more than a year, and in January, 1942, I 1944). It is said to block vagal action and the synapses tried it out. Since then I have watched its use spread between pre- and post-ganglionic fibres. Plain muscle and. glands remain unaffected. The intercostals are around the world. There is no doubt that it is filling a need. Developments in anaesthesia, during recent years penultimately affected, and the diaphragm last of all. There is no anaesthetic ,action. Elimination occurs have been mainly toward increased safety and comfort for the patient. Here is a drug which allows the sur- within 2 hours, partly by destruction in the liver and partly by excretion unchanged by the kidneys. Kidney geon to work more efficiently without increasing the hazard to the patient-a most important objective in lesions do not appear to contra-indicate the use of surgical progress. It is no wonder that the surgeons are curare (Griffith 1945). enthusiastic supporters of the use of curare in anaesthesia. METHOD OF USE I feel now that curare will enable us to use the nontoxic and controllable gas anaesthetic agents, particularly Premedication.-Omnopon-scopolamine techniques are cyclopropane and ethylene, in a wider variety of major excellent. Eithar scopolamine or atropirie is advised operations ; that it will reduce the use of spinal anaes- because one patient who had no premedication developed thesia for upper abdominal surgery with its attendant salivation, respiratory difficulties, and muscle-twitching, hazards ; and that it will afford more efficient anaesthesia which were successfully abolished by morphine gr. 1/6 with low concentrations of ether when that agent is and scopolamine gr. 1/150 (reported by Cullen 1943). chosen. Administration.—Exact dosage is best based on 0-5 Opinions about curare vary all the way from that of a mg. of curare per lb. body-weight. For practical purleading anaesthetist who states that " curare bids fair to poses in normal adults, I have injected up to 3 c.cm. of replace not only a great deal of deep ether anaesthesia but the solution ’ intravenously during 1-2 minutes, just a great deal of spinal anaesthesia as well," to the combefore the peritoneum is to be opened, the patient ment of one medical columnist, " why not learn to give an being under light anaesthesia. Relaxation with con" effective anaesthetic ? Personally I am not venturing tracted gut develops within 4 minutes, usually in 1-2 to prophesy, but I do know that curare will never take minutes. If relaxation is insufficient or the operation the place of the anaesthetist’s skill. The experience, prolonged, repeat doses of up to 2 c.cm. will effectively ability, and judgment of the anaesthetist are more import- restore relaxation. The maximum amount I have ant than any new agent or method, and I believethat given during one operation has been 10 c.cm. (case 3). curare should remain as just one more good thing in the Intercostal paralysis has only occurred after a single modern anaesthetist’s bag of tricks. It is not a plaything dose of more than 3 c.cm. (cases 1 and 2) ; it has been for the inexperienced, fleeting, lasting 3-5 minutes, and with gentle bag-comSUMMARY pression to supplement the diaphragm and so avoid The use of curare in anaesthesia has been reviewed with embarrassing the surgeon with " diaphragmatic flap " particular reference to its efficacy and safety as a muscle has never caused any anxiety. Complete respiratory
These
case-histories reassure
us
regarding the safety of
modern extracts of curare, when properly used, but I
,
-
’
76
paralysis has not been encountered. I have hadProstigmin’ (which neutralises curare at hand but have never used it.
always effects)
anccsthesia need never be ’deep but for satisfactory results should be into plane 2, because curare is inadequate as the sole relaxing agent (see case 4). (a) ’Pentothal’ (0-3-0-5 g.) with N20 and 0;j, resulting’ in lst plane anaesthesia, was first used. Excessive doses
Concomitant
(4-5 c.cm.), frequently repeated, were needed to secure adequate relaxation, and this was fleeting and divided by a narrow margin from intercostal paralysis, which was common. Results, were better with sufficient pentothal added to the N2O-O2 to secure 2nd plane anaesthesia,. (b) Pentothal-cyclopropane. Minimal pentothal for a pleasant induction followed by 0,Hc, maintained in light 2nd plane gave the best- results. Relaxation was complete and lasted —1 hour with intocostrin 2-3! c.cm. (see case 3). Intercostal depression was minimal, paralysis did not occur. Lightening anaesthesia to 1st plane, however, resulted in imperfect relaxation, and successful attempts to restore it with more curare inevitably produced intercostal paresis as
well.
(c) Ether anaesthesias with this preparation of curare have been described with very mixed opinions and results, I can see little point in employon the whole unfavourable. ingicurare with an agent itself possessed of profound relaxing qualities, as well as so many disadvantages (Mallinson
1943).
costals
1.05 : operation ended. Total intocostrin : 9-5 c.em.
recovered.
150/100.
1.15 :
BP
’
CASE 4.-Male, 19 yr. Small gut obstruction and perforation. Peritonitis, gravely ill. " D " risk. Ancesthesiapentothal 0,35 g. with N2O—O2. Serum and saline transfusion (1500 c.cm.). 3.25 PM : anaesthesia started and established in 1st plane. 3.35:intocostrin 1-5. c.cm. 3.37 : relaxation poor. 3.40 : intocostrin 2 c.cm. 345 : relaxation poor. 3.47 : intocostrin 2 c.cm. 3.49 : rela,xation, adequate. 3.55: relaxation receding. 4.10: intocostrin 2 c.cm. 4.12 : relaxation adequate ; peritoneum being suturedl 4.20 : relaxation receding. 4.25 : operation’ ended. This patient died 3 days later from his’ hopeless abdominal condition. CASE 5.-Male, 19 yr. Upper-lower laparotomy. Perforated colon. General peritonitis. Very ill. " C " risk. Anœsthesia:pentothal 0,45 g. with C3H6. Blood-transfusion (600 c.cm.) then saline. 12.20 PM : anaesthesia started. 12.49 : anaesthesia established in light 2nd plane: intocostrin 3 c.cm. 12.51 : relaxation not sufficient. 12.53: intocostrin 2 c.cm. 12.54 : relaxation excellent ; intercostals OK. 130 : relaxation receding ; intocostrin 1 c.can. for peritoneal suture. 1.50 : relaxation receding. 2.00 : operation ended.
CASE 6.-Male, 34 yr. Upper-lower abdominal. Repair of giant incisional hernia following gunshot wound of abdomen 9 months ago. Respiratory state complicated by residua of
abscess after wounding. Now healed. " B " risk. Anœsthesia:pentothal Ov g. with C,H6. 2.25 Pm anæsthesia started ; established in light 2nd plane. 2.35 : operation begun with extensive extraperitoneal dissection of sac and preparation for multiple fascial grafts. 4’08 : relaxation (case 7). requested for replacement and repair. Intocostrin 3 c.cm. Fall of blood-pressure having been described (Cullen 4.09 : relaxation excellent. 4.47 : relaxation receding ; 1943, 1944), records were kept in a number of cases, -- intocostrin 2 c.cm. 4.49: relaxation excellent. 5.20: relaxation receding ; peritoneum now closed. 5.45 : -operabut no alterations referable to the action of the drug were detected, even when used in very grave risks (cases tion ended. 4 and 5). CASE 7.-Male, 24 yr. Anastomosis and closure of colosNone of my cases has shown any untoward effects tomy. Intraperitoneal replacement. " A " risk. during or after operation referable to the action of Anœsthesia: pentothal 0,5 g.,with C3H6 ; deep lst plane ; curare. The small number of cases so far studied (40) 5.50 ?M : anæsthesia started. 6.25 : relaxation requested renders any figures of postoperative complications replacement ; intocostrin 3 c.cm. 6.27 : relaxation valueless, but no increase over more usual methods of for excellent. 6.30 : laryngoscopy ; cords only slightly abducted ; anaesthesia has been noted. patient coughed violently. 6.35 : relaxation receding.
S’ide effects.—With curare the vocal cords are said to be widely relaxed (Cole 1945). Except where dosage has been excessive and intercostal paralysis present (case 2) I have observed only moderate and fleeting effects on the larynx-in fact, I have had a patient cough violently from the stimulation of laryngoscopic observation
pulmonary
’
ILLUSTRATIVE CASES CONCLUSION
CASE
1.—Male, 39 years. Acute appendicitis. Pulmonary fibrosis and thickened pleura following recent blast injury and pneumonia. " B " risk. BP 135/75 mm. Hg. Ancesthesia:pentothal 0,75 g. with N2O-O2. 10.00 AM : anaesthesia started; 1st plane, deep. 10.10 : intocostrin 5 c.cm. ; 10.12 : relaxation excellent; complete intercostal paralysis. 10.22 : intercostal action returned. 10.27 : relaxation gone. 10.37 : operation ended ; BP 135/70.
Complete abdominal relaxation has hitherto only been obtainable by pushing a relatively toxic agent such as ether to a considerable depth or a relatively non-toxic
agent such
as cyclopropane or pentothal to a profound depth. It is widely admitted that physiological damage is largely proportional to depth of anaesthesia (Guedal 1937). This has resulted in a great swing over to spinal anaesthesia in recent years. The relaxation thus obtained CASE 2.-Male, 21 yr. Closure by anastomosis and intracan be perfect, but entails the formidable responsibility peritoneal replacement of upper abdominal transverse of injecting "sterile" solutions with " aseptic " precaucolostomy. " A " risk. BP 150/85 (leg reading). tions into the most defenceless cavity in the body. Ancesth,esia: pentothal 0-5 g. with N2O—O2. 5.35 rM : Local anaesthesia moreover is usually short in duration, anaesthesia started ; 1st plane.; 5-45 : intocostrin 3 c.cm.; often imperfect, and always time-consuming. 5.47 : relaxation fair ; 5.49 : relaxation good ; 6.00 : reIn curare we have an agent capable of producing 6.05: relaxation gone. 6.13: Intolaxation going off. relaxation comparable with spinal methods in the costrin 4 c.cm. 6;16 : relaxation excellent ; intercostals, presence of light anaesthesia, an ideal hitherto quite completely paralysed ; vocal cords well abducted. 6.25 : unattainable. Although I must emphasise strongly intercostals recovered. 6.35: relaxation receding. 6.40: my opinion that in no circumstances is intocostrin suitable for administration by other than the expert operation ended ; BP 160/100 (leg reading). CASE 3.-Male, 50 yr. Gastroduodenectomy. Chronic specialist, my experience to date convinces me that the ,
bronchitis and emphysema. "’ B" risk.
BP
145/100 (leg
reading). Anœsthesia: pentothal 0-4 g. with CH6. 10.15 AM: anaesthesia started ; 10.25 : operation started ; anaesthesia 10.37: Intocostrin 3-5 c.cm. established in 2nd plane. 10.38 : relaxation excellent; intercostals depressed (not paralysed). 10.50: intercostal depression disappeared. 12.05 : anastomosis completed ; further relaxation requested for exploration ; intocostrin 2 c.cm. 12.07 : relaxed. 12.38 : peritoneal suture beginning; intocostrin 2 c.cm. 12.39 : relaxed. 12.48 : anaesthesia now 1st plane ; relaxation insufficient ; intercostrin 2 c.cm. 12.49 : relaxed ; intercostals paralysed. 12.56 : peritoneum closed ; inter-
drug is well worth extensive trial. It is therefore with the object of encouraging extended trials by experienced workers in the field of anaesthesia in this country that I have been moved to attempt this preliminary report. REFERENCES
Baird, J. W., Adams, R. C. (1944) Proc. Mayo Clin. 19, 200. Cole, F. (1945) Anesthesiology, 6, 48. Cullen, S. C. (1943) Surgery, 14, 261. (1944) Anesthesiology, 5, 166. Griffith, H. R. (1944) J. Canad. wed. Ass. J. 50, 144. (1945) J. Amer. med Ass. 127, 642. Johnson, G. E. (1942) Anesthesiology, 3, 418. Guedal, A. E. (1937) Inhalation Anesthesia, New York. Mallinson, F. B. (1943) Lancet, ii, 729. -
curare it has been possible to perform operations such as a gastrectomy, using no other anaesthetic agent. This involves a revolutionary view of the physiological action of curare and is not easily explained, but from the purely clinical viewpoint it is reassuring to know that even such large doses of curare may be given without irreversible effect. During the recovery period Whitacre’s patients showed some tendency to bronchospasm,
,
increased bronchial secretion, and other undesirable side-effects, so that neither he nor I advocate using We are. just curare as a practical method of anaesthesia. glad to Bknow that doses up to 400 mg. have been given to human patients without fatal effect. An even more striking example of an overdose of curare has been reported by Robson of Toronto (1945). His patient. was an 8 lb. baby, two weeks old, undergoing operation for a complete diaphragmatic hernia under ether anaesthesia. By mistake a dose of 1 c.cm. of intocostrin (20 mg. curare) was given intravenously to improve relaxation. This was at least fifteen times the dose for such a patient. There was recommended immediate complete relaxation and also complete cessation of respiration. Dr. Robson cleverly maintained artificial respiration with endotracheal oxygen for more than three hours before there was the least sign of returning muscular activity. In the meantime, the surgeon hadcompleted the operation under ideal conditions, and eventually the baby recovered without permanent
damage.
relaxant in patients under cyclopropane, ether, and other general anaesthetic agents. In the light of more than three years’ clinical experience, curare is considered to be of value to expert an2esthetists by affording a better surgical field for abdominal operations with light and non-toxic anæsthesia. It will probably have a permanent place in anoesthesiology. REFERENCES
Baird, J. W., Adams, R. C. (1944) Proc. Mayo Clin. 19, 193. Bennett, A. E. (1940) J. Amer. med. Ass. 114, 322. Bernard, C. (1865) Bull. gén. Thérap. 69, 23. Cullen, S. E. (1943) Surgery, 14, 2 ; (1944) Anesthesiology, 5, 166. Gill, R. C. (1940) White Water and Black Magic, New York. Griffith, H. R., Johnson, G. E. (1942) Anesthesiology, 3, 418. Hudon, F. (1944) Laval méd. 9, 242. Knight, R. T. (1944) Minn. Med. 27, 667. Leech, B. C., Griffith, H. R. (1940) Canad. med. Ass. J. 42, 434. McIntyre, A. R., King. R. E. (1943) Science, 97, 69, 516. Robson, C. H. (1945) Read at Canadian Medical Association in Montreal.
Waters, R. M. (1944) Anesthesiology, 5, 618. Whitacre, R. J., Fisher, A. J. (1945) Ibid, 6, 124.
CURARE
IN
ANÆSTHESIA
F. BARNETT MALLINSON, M R C S, D A ANÆSTHETIST, PRINCESS BEATRICE, WOOLWICH MEMORIAL, AND ROYAL WATERLOO HOSPITALS; AND EATS
THE inception of curare in anaesthesia dates back to 1942 when Griffith and Johnson of Canada described hope they will not cause us to forget that when impro- their experiences in 25 cases. In 1943 Cullen published and clearly detailed observations on 1000 cases perly used curare is still a poison, capable of producing careful in the United States. The preparation of curare used death by respiratory paralysis. by these workers and employed in the present trial is The only side-effect which we have noted with curare, called ’Intocostrin’ and is manufactured by E. R. other than occasional respiratory depression, is a transiSquibb and Sons. The following observations are in which three developed patients intended ent bronchospasm as a preliminary report on a very promising after of the intravenous injection moderate immediately doses. This is recorded as a possible effect of curare, innovation. Intocostrin is a pure extract of curare, freed of alkawith no suggestion as to the cause-the patients resumed loids having toxic effects on heart and respiratory centre, normal breathing within one or two minutes. The assayed and standardised to contain 20 mg. preparations of curare we have used, intocostrin, and a biologically of the pure alkaloid per c.cm. (Baird and Adams 1944, new preparation D-tubocurarine,’ are not irritating to Cullen 1944). the subcutaneous tissues, and there has been no recorded Its purpose in anaesthesia, is to obtain maximum relaxacase of phlebitis or other similar complication. tion for abdominal surgery without the disadvantages ITS FUTURE of spinal or deep general anaesthesia. Curare neutraFive years ago when it was first suggested to me by Dr. lises the action of acetylcholine at the myoneural L. H. Wright, of New York, that curare might be useful junction thus acting only on voluntary muscle and in anaesthesia, I laughed at the ’idea. But I thought certain parasympathetic nerves (Cole 1945, - Griffith about it for more than a year, and in January, 1942, I 1944). It is said to block vagal action and the synapses tried it out. Since then I have watched its use spread between pre- and post-ganglionic fibres. Plain muscle and. glands remain unaffected. The intercostals are around the world. There is no doubt that it is filling a need. Developments in anaesthesia, during recent years penultimately affected, and the diaphragm last of all. There is no anaesthetic ,action. Elimination occurs have been mainly toward increased safety and comfort for the patient. Here is a drug which allows the sur- within 2 hours, partly by destruction in the liver and partly by excretion unchanged by the kidneys. Kidney geon to work more efficiently without increasing the hazard to the patient-a most important objective in lesions do not appear to contra-indicate the use of surgical progress. It is no wonder that the surgeons are curare (Griffith 1945). enthusiastic supporters of the use of curare in anaesthesia. METHOD OF USE I feel now that curare will enable us to use the nontoxic and controllable gas anaesthetic agents, particularly Premedication.-Omnopon-scopolamine techniques are cyclopropane and ethylene, in a wider variety of major excellent. Eithar scopolamine or atropirie is advised operations ; that it will reduce the use of spinal anaes- because one patient who had no premedication developed thesia for upper abdominal surgery with its attendant salivation, respiratory difficulties, and muscle-twitching, hazards ; and that it will afford more efficient anaesthesia which were successfully abolished by morphine gr. 1/6 with low concentrations of ether when that agent is and scopolamine gr. 1/150 (reported by Cullen 1943). chosen. Administration.—Exact dosage is best based on 0-5 Opinions about curare vary all the way from that of a mg. of curare per lb. body-weight. For practical purleading anaesthetist who states that " curare bids fair to poses in normal adults, I have injected up to 3 c.cm. of replace not only a great deal of deep ether anaesthesia but the solution ’ intravenously during 1-2 minutes, just a great deal of spinal anaesthesia as well," to the combefore the peritoneum is to be opened, the patient ment of one medical columnist, " why not learn to give an being under light anaesthesia. Relaxation with con" effective anaesthetic ? Personally I am not venturing tracted gut develops within 4 minutes, usually in 1-2 to prophesy, but I do know that curare will never take minutes. If relaxation is insufficient or the operation the place of the anaesthetist’s skill. The experience, prolonged, repeat doses of up to 2 c.cm. will effectively ability, and judgment of the anaesthetist are more import- restore relaxation. The maximum amount I have ant than any new agent or method, and I believethat given during one operation has been 10 c.cm. (case 3). curare should remain as just one more good thing in the Intercostal paralysis has only occurred after a single modern anaesthetist’s bag of tricks. It is not a plaything dose of more than 3 c.cm. (cases 1 and 2) ; it has been for the inexperienced, fleeting, lasting 3-5 minutes, and with gentle bag-comSUMMARY pression to supplement the diaphragm and so avoid The use of curare in anaesthesia has been reviewed with embarrassing the surgeon with " diaphragmatic flap " particular reference to its efficacy and safety as a muscle has never caused any anxiety. Complete respiratory
These
case-histories reassure
us
regarding the safety of
modern extracts of curare, when properly used, but I
,
-
’
76
paralysis has not been encountered. I have hadProstigmin’ (which neutralises curare at hand but have never used it.
always effects)
anccsthesia need never be ’deep but for satisfactory results should be into plane 2, because curare is inadequate as the sole relaxing agent (see case 4). (a) ’Pentothal’ (0-3-0-5 g.) with N20 and 0;j, resulting’ in lst plane anaesthesia, was first used. Excessive doses
Concomitant
(4-5 c.cm.), frequently repeated, were needed to secure adequate relaxation, and this was fleeting and divided by a narrow margin from intercostal paralysis, which was common. Results, were better with sufficient pentothal added to the N2O-O2 to secure 2nd plane anaesthesia,. (b) Pentothal-cyclopropane. Minimal pentothal for a pleasant induction followed by 0,Hc, maintained in light 2nd plane gave the best- results. Relaxation was complete and lasted —1 hour with intocostrin 2-3! c.cm. (see case 3). Intercostal depression was minimal, paralysis did not occur. Lightening anaesthesia to 1st plane, however, resulted in imperfect relaxation, and successful attempts to restore it with more curare inevitably produced intercostal paresis as
well.
(c) Ether anaesthesias with this preparation of curare have been described with very mixed opinions and results, I can see little point in employon the whole unfavourable. ingicurare with an agent itself possessed of profound relaxing qualities, as well as so many disadvantages (Mallinson
1943).
costals
1.05 : operation ended. Total intocostrin : 9-5 c.em.
recovered.
150/100.
1.15 :
BP
’
CASE 4.-Male, 19 yr. Small gut obstruction and perforation. Peritonitis, gravely ill. " D " risk. Ancesthesiapentothal 0,35 g. with N2O—O2. Serum and saline transfusion (1500 c.cm.). 3.25 PM : anaesthesia started and established in 1st plane. 3.35:intocostrin 1-5. c.cm. 3.37 : relaxation poor. 3.40 : intocostrin 2 c.cm. 345 : relaxation poor. 3.47 : intocostrin 2 c.cm. 3.49 : rela,xation, adequate. 3.55: relaxation receding. 4.10: intocostrin 2 c.cm. 4.12 : relaxation adequate ; peritoneum being suturedl 4.20 : relaxation receding. 4.25 : operation’ ended. This patient died 3 days later from his’ hopeless abdominal condition. CASE 5.-Male, 19 yr. Upper-lower laparotomy. Perforated colon. General peritonitis. Very ill. " C " risk. Anœsthesia:pentothal 0,45 g. with C3H6. Blood-transfusion (600 c.cm.) then saline. 12.20 PM : anaesthesia started. 12.49 : anaesthesia established in light 2nd plane: intocostrin 3 c.cm. 12.51 : relaxation not sufficient. 12.53: intocostrin 2 c.cm. 12.54 : relaxation excellent ; intercostals OK. 130 : relaxation receding ; intocostrin 1 c.can. for peritoneal suture. 1.50 : relaxation receding. 2.00 : operation ended.
CASE 6.-Male, 34 yr. Upper-lower abdominal. Repair of giant incisional hernia following gunshot wound of abdomen 9 months ago. Respiratory state complicated by residua of
abscess after wounding. Now healed. " B " risk. Anœsthesia:pentothal Ov g. with C,H6. 2.25 Pm anæsthesia started ; established in light 2nd plane. 2.35 : operation begun with extensive extraperitoneal dissection of sac and preparation for multiple fascial grafts. 4’08 : relaxation (case 7). requested for replacement and repair. Intocostrin 3 c.cm. Fall of blood-pressure having been described (Cullen 4.09 : relaxation excellent. 4.47 : relaxation receding ; 1943, 1944), records were kept in a number of cases, -- intocostrin 2 c.cm. 4.49: relaxation excellent. 5.20: relaxation receding ; peritoneum now closed. 5.45 : -operabut no alterations referable to the action of the drug were detected, even when used in very grave risks (cases tion ended. 4 and 5). CASE 7.-Male, 24 yr. Anastomosis and closure of colosNone of my cases has shown any untoward effects tomy. Intraperitoneal replacement. " A " risk. during or after operation referable to the action of Anœsthesia: pentothal 0,5 g.,with C3H6 ; deep lst plane ; curare. The small number of cases so far studied (40) 5.50 ?M : anæsthesia started. 6.25 : relaxation requested renders any figures of postoperative complications replacement ; intocostrin 3 c.cm. 6.27 : relaxation valueless, but no increase over more usual methods of for excellent. 6.30 : laryngoscopy ; cords only slightly abducted ; anaesthesia has been noted. patient coughed violently. 6.35 : relaxation receding.
S’ide effects.—With curare the vocal cords are said to be widely relaxed (Cole 1945). Except where dosage has been excessive and intercostal paralysis present (case 2) I have observed only moderate and fleeting effects on the larynx-in fact, I have had a patient cough violently from the stimulation of laryngoscopic observation
pulmonary
’
ILLUSTRATIVE CASES CONCLUSION
CASE
1.—Male, 39 years. Acute appendicitis. Pulmonary fibrosis and thickened pleura following recent blast injury and pneumonia. " B " risk. BP 135/75 mm. Hg. Ancesthesia:pentothal 0,75 g. with N2O-O2. 10.00 AM : anaesthesia started; 1st plane, deep. 10.10 : intocostrin 5 c.cm. ; 10.12 : relaxation excellent; complete intercostal paralysis. 10.22 : intercostal action returned. 10.27 : relaxation gone. 10.37 : operation ended ; BP 135/70.
Complete abdominal relaxation has hitherto only been obtainable by pushing a relatively toxic agent such as ether to a considerable depth or a relatively non-toxic
agent such
as cyclopropane or pentothal to a profound depth. It is widely admitted that physiological damage is largely proportional to depth of anaesthesia (Guedal 1937). This has resulted in a great swing over to spinal anaesthesia in recent years. The relaxation thus obtained CASE 2.-Male, 21 yr. Closure by anastomosis and intracan be perfect, but entails the formidable responsibility peritoneal replacement of upper abdominal transverse of injecting "sterile" solutions with " aseptic " precaucolostomy. " A " risk. BP 150/85 (leg reading). tions into the most defenceless cavity in the body. Ancesth,esia: pentothal 0-5 g. with N2O—O2. 5.35 rM : Local anaesthesia moreover is usually short in duration, anaesthesia started ; 1st plane.; 5-45 : intocostrin 3 c.cm.; often imperfect, and always time-consuming. 5.47 : relaxation fair ; 5.49 : relaxation good ; 6.00 : reIn curare we have an agent capable of producing 6.05: relaxation gone. 6.13: Intolaxation going off. relaxation comparable with spinal methods in the costrin 4 c.cm. 6;16 : relaxation excellent ; intercostals, presence of light anaesthesia, an ideal hitherto quite completely paralysed ; vocal cords well abducted. 6.25 : unattainable. Although I must emphasise strongly intercostals recovered. 6.35: relaxation receding. 6.40: my opinion that in no circumstances is intocostrin suitable for administration by other than the expert operation ended ; BP 160/100 (leg reading). CASE 3.-Male, 50 yr. Gastroduodenectomy. Chronic specialist, my experience to date convinces me that the ,
bronchitis and emphysema. "’ B" risk.
BP
145/100 (leg
reading). Anœsthesia: pentothal 0-4 g. with CH6. 10.15 AM: anaesthesia started ; 10.25 : operation started ; anaesthesia 10.37: Intocostrin 3-5 c.cm. established in 2nd plane. 10.38 : relaxation excellent; intercostals depressed (not paralysed). 10.50: intercostal depression disappeared. 12.05 : anastomosis completed ; further relaxation requested for exploration ; intocostrin 2 c.cm. 12.07 : relaxed. 12.38 : peritoneal suture beginning; intocostrin 2 c.cm. 12.39 : relaxed. 12.48 : anaesthesia now 1st plane ; relaxation insufficient ; intercostrin 2 c.cm. 12.49 : relaxed ; intercostals paralysed. 12.56 : peritoneum closed ; inter-
drug is well worth extensive trial. It is therefore with the object of encouraging extended trials by experienced workers in the field of anaesthesia in this country that I have been moved to attempt this preliminary report. REFERENCES
Baird, J. W., Adams, R. C. (1944) Proc. Mayo Clin. 19, 200. Cole, F. (1945) Anesthesiology, 6, 48. Cullen, S. C. (1943) Surgery, 14, 261. (1944) Anesthesiology, 5, 166. Griffith, H. R. (1944) J. Canad. wed. Ass. J. 50, 144. (1945) J. Amer. med Ass. 127, 642. Johnson, G. E. (1942) Anesthesiology, 3, 418. Guedal, A. E. (1937) Inhalation Anesthesia, New York. Mallinson, F. B. (1943) Lancet, ii, 729. -