- Email: [email protected]
ANTICHOLINERGIC PREMEDICATION
BRITISH JOURNAL OF ANAESTHESIA
910 REFERENCE
Evans, E. F., Proctor, J. D., Fratkin, M. J., Velandia, J., and Wasserman, A. J. (1975). Blood flow in muscle groups and drug absorption. Clin. Pharmacol. Ther., 17, 44. TEST DOSES IN EXTRADURAL ANALGESIA
All four catheters were subsequently used for introducing extradural local anaesthetic in the period after operation and no problems of high blockade were met. Although the glucose concentrations are less than that found in Dr Stirt's case (4.94 mmol litre"1) his patient had an abnormally increased blood glucose, 8.44 mmol litre" 1 compared with the normal range of 3.6-5.8 mmol litre"1. If Dr Stirt's catheter had entered the subarachnoid space, why wasn't the glucose concentration much closer to that of the blood, because c.s.f. concentrations follow closely those of blood ? How did the fluid manage to drip back when the end of the catheter was occluded? His case remains unconvincing and cannot be taken as evidence of transdural migration of the catheter. D. B. SCOTT Edinburgh REFERENCES
Scott, D. B. (1979). Test doses in extradural analgesia. Br.J. Anaesth., 51, 808. Stirt, J. A. (1978). Test doses in extradural analgesia. Br. J. Anaesth., 50, 1267. (1979). Test doses in extradural analgesia. Br. J. Anaesth., 51, 808. Sir,—Dr Scott does not yet seem persuaded that the case I reported (Stirt, 1978) involved transdural migration of an extradural catheter. I found Dr Scott's study of extradural fluid glucose concentrations of some interest, as much for the questions it raises as those it answers. I must congratulate him for succeeding where I failed in obtaining what appear to be the first measurements of extradural space glucose concentrations to be reported. Yet one question remains in my
J. A. STIRT Los Angeles REFERENCES
Plato (366 B.C.). The Republic, Book VII: 515-B. (Ed. J. D. Kaplan). New York City: Pocket Books, 1976. Stirt, J. A. (1978). Test doses in extradural analgesia. Br.J. Anaesth., 50, 1267. Tietz, N. W. (1976). Fundamentals of Clinical Chemistry, p. 242. Philadelphia: W. B. Saunders Co. ANTICHOLINERGIC PREMEDICATION
Sir,—I am writing about the methods of the study by Mirakhur, Dundee and Connolly (1979). The statistical analysis of the data was very extensive and carefully done. They have gone to great length to show statistical significance of heart rate changes of 3 and 4 beat min"1. Yet, although data are given regarding the weight of the patients involved, no attempt is made to correlate this information with changes in heart rate. Table I, for example, indicates that the difference in weight between the patients given hyoscine 1 mg orally and hyoscine 0.25 mg i.m. was 4 kg. A weight difference of greater than 10% as in this case, would almost certainly affect the clinical measurements that were made so carefully. Because the authors obviously have the data it would seem reasonable that their results be reworked on a dose/unit weight basis, as was done for the administration of the induction agent. As an aside, it is interesting to note an initial slight decrease in heart rate at the lower dose ranges, although this is statistically insignificant. I. J. GILMOUR
Minneapolis, U.S.A.
Downloaded from http://bja.oxfordjournals.org/ at RMIT University Library on July 13, 2015
Sir,—I am sorry that Dr Stirt (Stirt, 1979) should assume that I believed glucose and lignocaine had similar molecular structures. However, both compounds cross capillary walls easily and rapidly and therefore both will move in the direction of their concentration gradients—glucose into the extradural space and lignocaine out of it. At the time of writing my previous letter (Scott, 1979), I only had the evidence of the lignocaine concentrations to make my case. However, since the publication of Dr Stirt's letter (1978), I have obtained fluid from the extradural space of four patients. It may be relevant that all were surgical patients who had received 20 ml of local anaesthetic solution—about twice the dose used in relieving labour pain. In three, the fluid was seen dripping slowly from the Milipore filter attached to the catheter end, and with gentle aspiration 0.2 ml, 0.5 ml and 1.5 ml respectively were obtained 10-15 min after injection. Although not all the fluid would have been in the extradural space, especially in the case of the two smaller volume samples, the glucose content was 0.05 mmol litre" 1 , 1.1 mmol litre"1 and 4.4 mmol litre"1. In the fourth patient 2 ml was obtained by spontaneous refilling of the 20-ml glass syringe attached to the Milipore filter. In this case the glucose content was 1.7 mmol litre"1.
mind when I look at his values. What contribution was made by local anaesthetic glucose concentration? As I noted earlier, 3% chloroprocaine contains a small but significant amount of glucose (0.39 mmol litre"1). Did the local anaesthetic solution used by Dr Scott perhaps have a similar, or even greater, glucose content? This makes me suspicious of the smallest value he reports, and perhaps the others as well. Let us assume for the moment that there is indeed an appreciable movement of glucose into whatever fluid occupies the extradural space. Dr Scott points out, correctly, that the blood glucose concentration in the case I reported was "abnormally high" (8.44 mmol litre"1). This was undoubtedly a result of a continuous i.v. infusion of 5% dextrose in water which had been running for about 5 h before the administration of anaesthesia. In any case, one would expect the c.s.f. glucose not to "follow closely" but rather to be approximately 60-70% of that in blood (Tietz, 1976). Indeed, as I reported earlier, catheter fluid glucose was 4.94 mmol litre" 1 with a simultaneous blood glucose concentration of 8.44 mmol litre"1. I attribute the fluid return past the occluded end of the catheter to the relatively high pressure in the subarachnoid space, where I believe the end of the catheter resided. "Like ourselves . . . they see only their own shadows, or the shadows of one another, which the fire throws on the opposite wall of the cave" (Plato, 366 B.C.). I suggest that the side of the dura upon which one believes the shadow of the extradural catheter in question fell is, in the end, a matter of how one chooses to interpret the shadows of data and doubt cast by Dr Scott and myself.
CORRESPONDENCE
911
REFERENCE
REFERENCE
Mirakhur, R. K., Dundee, J. W., and Connolly, S. D. R. (1979). Studies of drugs given before anaesthesia. XVII: Anticholinergic premedication. Br. J. Anaesth., 51, 339.
Watkins, J., Udnoon, S., Appleyard, T. N., and Thornton, J. A. (1976). Identification and quantification of hypersensitivity reactions to i.v. anaesthetic agents. Br. J. Anaesth., 48, 457.
Sir,—Even though some small changes in heart rate were shown to be statistically significant, no clinical significance was attached to such changes. The study was primarily done to assess the overall need of anticholinergic premedication in patients undergoing minor surgery and as such drugs were not administered on a weight basis. However, Dr Gilmour's comment has aroused our interest in this subject and we plan to present the results in a separate communication. Belfast
ADVERSE REACTIONS TO ANAESTHETIC AGENTS
Sir,—There has been much recent interest in the mechanisms which underlie adverse reactions to i.v. anaesthetic drugs. Watkins and colleagues (1976) have shown convincingly that complement activation via the alternate pathway is a frequent mechanism underlying the adverse reaction to Althesin. It is less certain, however, which other drugs can activate the alternate complement pathway. We would like to report a severe reaction in a healthy 26-yr-old man undergoing cautery of nasal mucosa and catheterization of the right eustachean tube. There was no history of allergy other than nasal stuffiness which was aggravated by exposure to grass cuttings. More than 20 years ago he had been anaesthetized for the treatment of an upper limb fracture; details of the drugs used are not available, and he had not received anaesthesia on any other occasion. The patient had an immediate histamine-mediated reaction causing profound and prolonged hypotension after gallamine 20 mg, thiopentone 450 mg and suxamethonium 125 mg i.v. Loss of circulating blood volume responded to the infusion of plasma and the vigorous application of conventional resuscitation measures. Serial blood samples showed massive conversion of complement C3 via the alternate pathway. Three hours after the start of the reaction 60% of the C3 complement had undergone conversion, which is greater than has ever been recorded after an Althesin reaction. We conclude that gallamine, thiopentone and suxamethonium in combination, and perhaps individually, may trigger the alternate complement pathway in a susceptible individual, with life-threatening consequences. DAVID T. BROWN DAVID BEAMISH Edinburgh
R. W. JOHNSON
Bristol REFERENCES
Crawford, J. S. (1979). Experience with spinal analgesia in a British obstetric unit. Br.J. Anaesth., 51, 431. Bridenbaugh, L. D., and Moore, D. C. (1964). Does repeated heat sterilization of local anaesthetic drugs affect potency ? Anesthesiology, 25, 372. INADVERTENT ADMINISTRATION OF 1 0 0 % OXYGEN DURING ANAESTHESIA
Sir,—We read the correspondence on this subject with interest (Paymaster, 1978; Dodd, 1979) as we have also encountered similar difficulties with the Cape Waine Mk III anaesthetic machine. On our machines the "emergency" oxygen switch is a push switch, spring-loaded, requiring a half turn to lock it into position. We have overcome the problem by requesting Cape Engineering Ltd to remove the mechanical stop. This ensures that the oxygen bypass cannot be left on inadvertently and thus solves the problem. D. G. LARARD D. G. TWEEDIE
Warzuick REFERENCES
Dodd, K. W. (1979). Inadvertent administration of 100% oxygen during anaesthesia. Br. J. Anaesth., 51, 573. Paymaster, N. J. (1978). Inadvertent administration of 100% oxygen during anaesthesia. Br.J. Anaesth., 50,1268.
Downloaded from http://bja.oxfordjournals.org/ at RMIT University Library on July 13, 2015
R. K. MIRAKHUR J. W. DUNDEE
AMETHOCAINE
Sir,—Dr Crawford mentioned the use of hyperbaric solutions of cinchocaine, lignocaine and prilocaine (Crawford, 1979). Many anaesthetists who have used amethocaine for spinal anaesthesia consider it to be superior to these drugs and would greatly value its availability in this country. Why are drug companies reluctant to market a suitable preparation of amethocaine in Britain ? Approaches to drug marketing concerns reap no harvest, and little explanation is given for this negative response. Could it be that the quantity used would be inadequate to justify the expensive and time-consuming process of reintroducing the drug ? It seems so unsatisfactory that we should import disposable spinal anaesthesia sets from the U.S.A. with empty slots from which amethocaine ampoules have been removed! Amethocaine survives well the process of sterilization by autoclaving (Bridenbaugh and Moore, 1964). Ampoules containing the dry salt are particularly stable, and are readily mixed with dextrose solution to produce hyperbaric or hypobaric solutions suitable for subarachnoid administration.
910 REFERENCE
Evans, E. F., Proctor, J. D., Fratkin, M. J., Velandia, J., and Wasserman, A. J. (1975). Blood flow in muscle groups and drug absorption. Clin. Pharmacol. Ther., 17, 44. TEST DOSES IN EXTRADURAL ANALGESIA
All four catheters were subsequently used for introducing extradural local anaesthetic in the period after operation and no problems of high blockade were met. Although the glucose concentrations are less than that found in Dr Stirt's case (4.94 mmol litre"1) his patient had an abnormally increased blood glucose, 8.44 mmol litre" 1 compared with the normal range of 3.6-5.8 mmol litre"1. If Dr Stirt's catheter had entered the subarachnoid space, why wasn't the glucose concentration much closer to that of the blood, because c.s.f. concentrations follow closely those of blood ? How did the fluid manage to drip back when the end of the catheter was occluded? His case remains unconvincing and cannot be taken as evidence of transdural migration of the catheter. D. B. SCOTT Edinburgh REFERENCES
Scott, D. B. (1979). Test doses in extradural analgesia. Br.J. Anaesth., 51, 808. Stirt, J. A. (1978). Test doses in extradural analgesia. Br. J. Anaesth., 50, 1267. (1979). Test doses in extradural analgesia. Br. J. Anaesth., 51, 808. Sir,—Dr Scott does not yet seem persuaded that the case I reported (Stirt, 1978) involved transdural migration of an extradural catheter. I found Dr Scott's study of extradural fluid glucose concentrations of some interest, as much for the questions it raises as those it answers. I must congratulate him for succeeding where I failed in obtaining what appear to be the first measurements of extradural space glucose concentrations to be reported. Yet one question remains in my
J. A. STIRT Los Angeles REFERENCES
Plato (366 B.C.). The Republic, Book VII: 515-B. (Ed. J. D. Kaplan). New York City: Pocket Books, 1976. Stirt, J. A. (1978). Test doses in extradural analgesia. Br.J. Anaesth., 50, 1267. Tietz, N. W. (1976). Fundamentals of Clinical Chemistry, p. 242. Philadelphia: W. B. Saunders Co. ANTICHOLINERGIC PREMEDICATION
Sir,—I am writing about the methods of the study by Mirakhur, Dundee and Connolly (1979). The statistical analysis of the data was very extensive and carefully done. They have gone to great length to show statistical significance of heart rate changes of 3 and 4 beat min"1. Yet, although data are given regarding the weight of the patients involved, no attempt is made to correlate this information with changes in heart rate. Table I, for example, indicates that the difference in weight between the patients given hyoscine 1 mg orally and hyoscine 0.25 mg i.m. was 4 kg. A weight difference of greater than 10% as in this case, would almost certainly affect the clinical measurements that were made so carefully. Because the authors obviously have the data it would seem reasonable that their results be reworked on a dose/unit weight basis, as was done for the administration of the induction agent. As an aside, it is interesting to note an initial slight decrease in heart rate at the lower dose ranges, although this is statistically insignificant. I. J. GILMOUR
Minneapolis, U.S.A.
Downloaded from http://bja.oxfordjournals.org/ at RMIT University Library on July 13, 2015
Sir,—I am sorry that Dr Stirt (Stirt, 1979) should assume that I believed glucose and lignocaine had similar molecular structures. However, both compounds cross capillary walls easily and rapidly and therefore both will move in the direction of their concentration gradients—glucose into the extradural space and lignocaine out of it. At the time of writing my previous letter (Scott, 1979), I only had the evidence of the lignocaine concentrations to make my case. However, since the publication of Dr Stirt's letter (1978), I have obtained fluid from the extradural space of four patients. It may be relevant that all were surgical patients who had received 20 ml of local anaesthetic solution—about twice the dose used in relieving labour pain. In three, the fluid was seen dripping slowly from the Milipore filter attached to the catheter end, and with gentle aspiration 0.2 ml, 0.5 ml and 1.5 ml respectively were obtained 10-15 min after injection. Although not all the fluid would have been in the extradural space, especially in the case of the two smaller volume samples, the glucose content was 0.05 mmol litre" 1 , 1.1 mmol litre"1 and 4.4 mmol litre"1. In the fourth patient 2 ml was obtained by spontaneous refilling of the 20-ml glass syringe attached to the Milipore filter. In this case the glucose content was 1.7 mmol litre"1.
mind when I look at his values. What contribution was made by local anaesthetic glucose concentration? As I noted earlier, 3% chloroprocaine contains a small but significant amount of glucose (0.39 mmol litre"1). Did the local anaesthetic solution used by Dr Scott perhaps have a similar, or even greater, glucose content? This makes me suspicious of the smallest value he reports, and perhaps the others as well. Let us assume for the moment that there is indeed an appreciable movement of glucose into whatever fluid occupies the extradural space. Dr Scott points out, correctly, that the blood glucose concentration in the case I reported was "abnormally high" (8.44 mmol litre"1). This was undoubtedly a result of a continuous i.v. infusion of 5% dextrose in water which had been running for about 5 h before the administration of anaesthesia. In any case, one would expect the c.s.f. glucose not to "follow closely" but rather to be approximately 60-70% of that in blood (Tietz, 1976). Indeed, as I reported earlier, catheter fluid glucose was 4.94 mmol litre" 1 with a simultaneous blood glucose concentration of 8.44 mmol litre"1. I attribute the fluid return past the occluded end of the catheter to the relatively high pressure in the subarachnoid space, where I believe the end of the catheter resided. "Like ourselves . . . they see only their own shadows, or the shadows of one another, which the fire throws on the opposite wall of the cave" (Plato, 366 B.C.). I suggest that the side of the dura upon which one believes the shadow of the extradural catheter in question fell is, in the end, a matter of how one chooses to interpret the shadows of data and doubt cast by Dr Scott and myself.
CORRESPONDENCE
911
REFERENCE
REFERENCE
Mirakhur, R. K., Dundee, J. W., and Connolly, S. D. R. (1979). Studies of drugs given before anaesthesia. XVII: Anticholinergic premedication. Br. J. Anaesth., 51, 339.
Watkins, J., Udnoon, S., Appleyard, T. N., and Thornton, J. A. (1976). Identification and quantification of hypersensitivity reactions to i.v. anaesthetic agents. Br. J. Anaesth., 48, 457.
Sir,—Even though some small changes in heart rate were shown to be statistically significant, no clinical significance was attached to such changes. The study was primarily done to assess the overall need of anticholinergic premedication in patients undergoing minor surgery and as such drugs were not administered on a weight basis. However, Dr Gilmour's comment has aroused our interest in this subject and we plan to present the results in a separate communication. Belfast
ADVERSE REACTIONS TO ANAESTHETIC AGENTS
Sir,—There has been much recent interest in the mechanisms which underlie adverse reactions to i.v. anaesthetic drugs. Watkins and colleagues (1976) have shown convincingly that complement activation via the alternate pathway is a frequent mechanism underlying the adverse reaction to Althesin. It is less certain, however, which other drugs can activate the alternate complement pathway. We would like to report a severe reaction in a healthy 26-yr-old man undergoing cautery of nasal mucosa and catheterization of the right eustachean tube. There was no history of allergy other than nasal stuffiness which was aggravated by exposure to grass cuttings. More than 20 years ago he had been anaesthetized for the treatment of an upper limb fracture; details of the drugs used are not available, and he had not received anaesthesia on any other occasion. The patient had an immediate histamine-mediated reaction causing profound and prolonged hypotension after gallamine 20 mg, thiopentone 450 mg and suxamethonium 125 mg i.v. Loss of circulating blood volume responded to the infusion of plasma and the vigorous application of conventional resuscitation measures. Serial blood samples showed massive conversion of complement C3 via the alternate pathway. Three hours after the start of the reaction 60% of the C3 complement had undergone conversion, which is greater than has ever been recorded after an Althesin reaction. We conclude that gallamine, thiopentone and suxamethonium in combination, and perhaps individually, may trigger the alternate complement pathway in a susceptible individual, with life-threatening consequences. DAVID T. BROWN DAVID BEAMISH Edinburgh
R. W. JOHNSON
Bristol REFERENCES
Crawford, J. S. (1979). Experience with spinal analgesia in a British obstetric unit. Br.J. Anaesth., 51, 431. Bridenbaugh, L. D., and Moore, D. C. (1964). Does repeated heat sterilization of local anaesthetic drugs affect potency ? Anesthesiology, 25, 372. INADVERTENT ADMINISTRATION OF 1 0 0 % OXYGEN DURING ANAESTHESIA
Sir,—We read the correspondence on this subject with interest (Paymaster, 1978; Dodd, 1979) as we have also encountered similar difficulties with the Cape Waine Mk III anaesthetic machine. On our machines the "emergency" oxygen switch is a push switch, spring-loaded, requiring a half turn to lock it into position. We have overcome the problem by requesting Cape Engineering Ltd to remove the mechanical stop. This ensures that the oxygen bypass cannot be left on inadvertently and thus solves the problem. D. G. LARARD D. G. TWEEDIE
Warzuick REFERENCES
Dodd, K. W. (1979). Inadvertent administration of 100% oxygen during anaesthesia. Br. J. Anaesth., 51, 573. Paymaster, N. J. (1978). Inadvertent administration of 100% oxygen during anaesthesia. Br.J. Anaesth., 50,1268.
Downloaded from http://bja.oxfordjournals.org/ at RMIT University Library on July 13, 2015
R. K. MIRAKHUR J. W. DUNDEE
AMETHOCAINE
Sir,—Dr Crawford mentioned the use of hyperbaric solutions of cinchocaine, lignocaine and prilocaine (Crawford, 1979). Many anaesthetists who have used amethocaine for spinal anaesthesia consider it to be superior to these drugs and would greatly value its availability in this country. Why are drug companies reluctant to market a suitable preparation of amethocaine in Britain ? Approaches to drug marketing concerns reap no harvest, and little explanation is given for this negative response. Could it be that the quantity used would be inadequate to justify the expensive and time-consuming process of reintroducing the drug ? It seems so unsatisfactory that we should import disposable spinal anaesthesia sets from the U.S.A. with empty slots from which amethocaine ampoules have been removed! Amethocaine survives well the process of sterilization by autoclaving (Bridenbaugh and Moore, 1964). Ampoules containing the dry salt are particularly stable, and are readily mixed with dextrose solution to produce hyperbaric or hypobaric solutions suitable for subarachnoid administration.