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British Journal of Anaesthesia 1996; 76: 881–890

CORRESPONDENCE Suxamethonium and auditory evoked potentials Sir,—I read with interest the article by Brunner and colleagues on the relationship between suxamethonium and cortical auditory evoked potentials [1]. The focus of the article was the hypothesis that suxamethonium may cause arousal of anaesthetized patients, but no plausible explanations were offered by the authors as to the possible mechanism. I suspect that the authors overlooked the effects of neuromuscular blockers on the muscles of the tympanum (tensor tympani and stapedius) which are the most sensitive muscles in the body to the action of blocking drugs. For example, there is considerable literature on the early diagnosis of myasthenia gravis by testing the reflex tensioning of the middle ear ossicles with impedance techniques. Thus the effect of suxamethonium on the auditory evoked response may not be concerned with arousal. Instead it may merely be the result of abolishing the tensioning reflex mediated by the stapedius, allowing a much larger mechanical signal through to the inner ear and therefore causing a larger stimulus up the auditory nerve. The authors even cited a reference reporting the absence of the “arousal” effect of suxamethonium in the presence of previous non-depolarizing paralysis (ref. [10]) which is what one would expect: when the stapedius has been blocked totally, it cannot be blocked further. The results of this article are nevertheless interesting. The discussion section, however, might perhaps have been reduced to a single 10-line paragraph had the authors taken into account the physiology of the stapedius reflex. J. PONTE King’s College Hospital London 1. Brunner MD, Nathwani D, Rich PA, Thornton C, Doré CJ. Effect of suxamethonium on the auditory evoked response in humans. British Journal of Anaesthesia 1996; 76: 34–37.

2. Mori K, Iwabuchi K, Fujita M. The effects of depolarizing muscle relaxants on the electroencephalogram and the circulation during halothane anaesthesia in man. British Journal of Anaesthesia 1973; 45: 604–610.

Extradural clonidine for postoperative pain relief Sir,—With regard to a recent letter by Nishikawa [1] criticizing pain assessment by Lee and Rubin [2], we feel that, as our recent article [3] used similar methodology to theirs, we should reply to the points raised. First, Nishikawa questions that objective assessment of pain is possible in small children. This is an area of obvious difficulty and is the reason why a previously validated [4] objective pain scoring system was used in both studies [2, 3], This was used by staff [2] or parents [3] to decide when analgesia was necessary. Quite how this makes bias “likely” when observations of randomized groups are being made double-blind is unclear to us. Nishikawa also states that he “cannot exclude. . . that intense sedation induced by extradural clonidine (with local anaesthetics) would make estimation of pain intensity impossible”. He cites his own study [5] in support of this. However, this article makes no attempt to assess pain in its methodology. In addition, all patients were adults who were premedicated and sedated during operation. Despite this, and one group receiving a larger mean dose of clonidine (3.3 ␮g kg91) than in the paediatric studies (2 ␮g kg91), none was “sedated to the degree that she could not respond to verbal commands”. This suggests that ability to communicate was retained. Lee and Rubin [2] found it difficult to separate analgesia and sedation in their patients receiving extradural clonidine. They also used sedative premedication. In our study [3] no premedication was used and we confirmed that clonidine 2 ␮g kg91 provided a longer duration of analgesia than adrenaline 1 : 200 000 when added to caudal 0.25 % bupivacaine 1 ml kg91 (medians : clonidine 5.8 h, adrenaline 3.2 h; P
0.05). There was no difference in time to spontaneous eye opening after cessation of anaesthesia (medians : clonidine 21 min, adrenaline 20 min) or sedation scores at 4 h (medians : clonidine 0, adrenaline 0). Only three patients in the clonidine group (total 20) required analgesia at 4 h when median sedation score was 0 (eyes open spontaneously). Therefore, it is our contention that sedation does not preclude estimation of pain in children given extradural clonidine 2 ␮g kg91 in combination with local anaesthetic, but that the use of other sedative drugs may introduce this difficulty. B. COOK E. DOYLE Department of Anaesthesia Royal Infirmary of Edinburgh Edinburgh

Sir,–Our study showed that suxamethonium had an arousal effect according to the auditory evoked response (AER). In the discussion section of our article, we outlined the possible causes of this effect and, according to the literature, felt that cortical stimulation secondary to increased muscle spindle activity after muscle fasciculation or direct spindle stimulation by suxamethonium itself, may be responsible for the arousal pattern which we observed. Theoretically, as Dr Ponte points out, paralysis of the stapedius by suxamethonium could increase the input up the auditory nerve resulting in an AER response similar to that seen with arousal. However, if this were so, all neuromuscular blocking drugs would have an arousal effect on the AER. There is currently no evidence in the literature to support this theory. In fact, in an article published recently in this journal [1], Richmond and colleagues showed that vecuronium had no effect on the AER. Regarding the article by Mori, Iwabuchi and Fujita [2], Dr Ponte is correct in saying that these authors found that suxamethonium failed to cause arousal in the presence of previous non-depolarizing paralysis. However, the authors also found that non-depolarizing drugs failed to cause arousal, which they should have if the stapedius reflex were a factor. On the other hand, their findings support our assertion that arousal after suxamethonium may result from muscle spindle stimulation, because its effect on the EEG can be blocked by non-depolarizing blockers which prevent fasciculation. Also, Mori and colleagues did not measure the AER in their subjects. They examined instead EEG responses where auditory reflexes are less important. M. D. BRUNNER C. THORNTON D. E. F. NEWTON Northwick Park Hospital Harrow, Middlesex

1. Nishikawa T. Extradural clonidine for postoperative pain relief. British Journal of Anaesthesia 1996; 76: 171. 2. Lee JJ, Rubin AP. Comparison of a bupivacaine-clonidine mixture with plain bupivacaine for caudal analgesia in children. British Journal of Anaesthesia 1994; 74: 258–262. 3. Cook B, Grubb DJ, Aldridge LA, Doyle E. Comparison of the effects of adrenaline, clonidine and ketamine on the duration of caudal analgesia produced by bupivacaine in children. British Journal of Anaesthesia 1995; 75: 698–701. 4. Hanallah RS, Broadman LS, Belman AB, Abramowitz MD, Epstein BS. Comparison of caudal and ilioinguinal nerve blocks for control of post-orchidopexy pain in pediatric ambulatory surgery. Anesthesiology 1987; 66: 832–834. 5. Nishikawa T, Dohi S. Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. Anesthesiology 1990; 73: 853–859.

1. Richmond CE, Matson A, Thornton C, Doré CJ, Newton DEF. Effect of neuromuscular block on depth of anaesthesia as measured by the auditory evoked response. British Journal of Anaesthesia 1996; 76: 446–448.

Sir,—I read with interest the article by Cook and colleagues [1] insisting that sedation does not preclude postoperative pain

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assessment in small children receiving extradural clonidine and local anaesthetic. I cannot wholly agree with their contention. First, I think that the pain scoring system [2] used in their study did not necessarily provide real assessment of postoperative pain intensity, because estimation of pain with this method is likely to be affected by other discomforts (for example, sleep, hunger or thirst, etc.). Second, paediatric patients received analgesics only when the parent judged its requirements in their study. Therefore, some bias caused by individual variability in the parent’s care may be introduced in the quantitative assessment of analgesia. I still believe that the most objective assessment of postoperative pain can be judged only by the same attending staff, blinded to the treatment, irrespective of patient age, and that it is difficult to separate analgesia from sedation in paediatric patients, as Lee and Rubin [3] found. More importantly, it appears curious to me that Cook and colleagues did not observe significant sedation in patients receiving caudal extradural clonidine 2 ␮g kg91 with 0.25 % bupivacaine 1 ml kg91 compared with those receiving caudal adrenaline 5 ␮g kg91 with 0.25 % bupivacaine 1 ml kg91, as the smaller dose of extradural clonidine of less than 2 ␮g kg91 also produced intense sedation in adults in our study [4]. T. NISHIKAWA Tsukuba, Japan 1. Cook B, Grubb DJ, Aldridge LA, Doyle E. Comparison of the effects of adrenaline, clonidine and ketamine on the duration of caudal analgesia produced by bupivacaine in children. British Journal of Anaesthesia 1995; 75: 698–701. 2. Hannallah RS, Broadman LM, Belman AB, Abramowitz MD, Epstein BS. Comparison of caudal and ilioinguinal/ iliohypogastric nerve blocks for control of post-orchiopexy pain in pediatric ambulatory surgery. Anesthesiology 1987; 66: 832–834. 3. Lee JJ, Rubin AP. Comparison of a bupivacaine-clonidine mixture with plain bupivacaine for caudal analgesia in children. British Journal of Anaesthesia 1994; 72: 258–262. 4. Nishikawa T, Dohi S. Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. Anesthesiology 1990; 73: 853–859.

Aprotinin during liver transplantation Sir,—We were interested to read the double-blind, randomized study by Milroy and colleagues [1] on haemodynamic stability after administration of aprotinin during orthotopic liver transplantation (OLT). We wish to make the following observations. Aprotinin reduces transfusion requirements and blood loss in patients undergoing heart surgery [2]. However, this beneficial effect has never been assessed in patients undergoing OLT. In the reference mentioned by the authors [3], as in all articles published previously, comparisons were made with historical controls. Moreover, aprotinin did not significantly reduce oozing during OLT in the only randomized study [4]. In the introduction to the article, the authors wrote “the aim of the present study was to determine if aprotinin influenced blood loss, blood product requirements…”. We were disappointed not to find the answer in the results as they studied 55 patients, a large sample, in a controlled, randomized study, but failed to answer the question: does aprotinin reduce blood loss in OLT? C. LENTSCHENER D. BENHAMOU Département D’Anesthésie-Réanimation Hôpital Antoine Béclère Clamart, France 1. Milord JS, Cottam S, Tan KC, Hilmi I, Oyesola B. Improved haemodynamic stability with administration of aprotinin during liver transplantation. British Journal of Anaesthesia 1995; 75: 747–751. 2. Bidstrup BP, Royston D, Sapsford RN, Tauylor KM. Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (Trasylol). Journal of Thoracic and Cardiovascular Surgery 1989; 97: 364–372. 3. Grosse H, Lobbes W, Frambach M, Ringe B, Barthels M. Influence of high dose aprotinin on hemostasis and blood requirement in orthotopic liver transplantation. Seminars in Thrombosis and Hemostasis 1993; 19: 302–305.

4. Groh J, Welte M, Azad SC, Forst H, Pratschke E, Kratzer MAA. Does aprotinin affect blood loss in liver transplantation? Lancet 1992; 340: 173. Sir,—We appreciate the chance to reply to the comments of Drs Lentschener and Benhamou. Blood loss values were omitted from this article. Intraoperative blood loss was higher in the placebo group (median 4676.5 ml (interquartile range 3060–6230 ml)) compared with the aprotinin-treated group (3467.5 (1770–5245) ml). These data were subjected to statistical analysis using non-parametric tests. The differences in intraoperative blood loss between the two groups did not reach statistical significance. There was also a trend towards reduced blood transfusion requirements during and after operation in the aprotinin-treated group, but again this was not statistically significant. Even though Lentschener and Benhamou consider that our study was conducted on a large group of patients, in retrospect we are of the opinion that this study did not have sufficient statistical power to either support or refute the question it was designed to answer, namely does aprotinin reduce blood loss during orthotopic liver transplantation (OLT)? We have realized that patient selection may not have been ideal in helping to answer this important question. Our original approach for this study was to include all suitable patients undergoing OLT for chronic or acute hepatic failure. This led to the inclusion of a high proportion of “low risk” patients (48 % in the placebo group and 29 % in the aprotinin group) with a preoperative diagnosis of primary biliary cirrhosis and primary sclerosing cholangitis. We now consider these patients to be at low risk of intraoperative fibrinolysis, and no longer administer prophylactic antifibrinolytic therapy. It was our intention to publish this article merely to highlight the interesting and previously (to our knowledge) unreported finding that administration of aprotinin during OLT can confer statistically significant improvements in haemodynamic stability during the post-reperfusion phase. We are currently conducting a more powerful randomized, double-blind study in patients we consider to be at high risk of intraoperative fibrinolysis and bleeding during OLT to definitively answer Lentschener and Benhamou’s question. S. COTTAM S. J. MILROY Department of Anaesthetics and Liver Transplantation King’s College Hospital, London

Aortic stent surgery Sir,—We were interested to read the case report by Greiff, Thompson and Langham [1]. To our knowledge there are four centres in the UK, including Leicester, that are involved in endoluminal repair of abdominal aortic aneurysm. At the 1995 annual scientific meeting of the Vascular Surgical Society, the results of several of the centres were presented, and also recently in Sydney [2]. It is interesting to note that the procedure is not always as straightforward as suggested in the case report by Greiff, Thompson and Langham. Failure to deploy the stent is not uncommon [3]. The need to convert to an open operation may occur in up to 35 % of patients. Although there is a definite learning curve with mortality being reduced the more experienced the team, perioperative mortality is approximately 10 % [4]. Late failure of the graft has also been described. There are several reasons for these problems. The technique is relatively new and during the early stages of development there is a tendency to use the technique in those patients where open surgery is very likely to result in the death of the patient. For example, the patient may have significant cardiovascular disease and death is a significant risk whatever the operation. As indicated in the article of Greiff, Thompson and Langham, the main advantage for patients is that when the procedure succeeds smoothly, the postoperative course is usually less complicated than after open surgery. The patient’s trachea can usually be extubated early and the patient may be mobilized early. This improved postoperative course may not, however, outweigh the risk of hypotension that occurs while the balloons are inflated to deploy the stent during the procedure. Studies examining the advantages of this technique compared with open surgery in

Correspondence different groups of patients are necessary and also studies evaluating the anaesthetic techniques used. A.P. BARANOWSKI M. ADISESHIAH UCL Hospitals London 1. Greiff JMC, Thompson MM, Langham BT. Anaesthetic implications of aortic stent surgery. British Journal of Anaesthesia 1995; 75: 779–781. 2. Adiseshiah M, Mcarthy T, Howling S, Lee W, Shaw P. A comparison of intraoperative angiographic estimation with 3D spiral reconstruction of aortic size for endoluminal repair of abdominal aortic aneurysm. Journal of Endovascular Surgery 1996; 3: 80–81. 3. Chuter TAM, Wendt G, Hopkinson BR, Scott RA, Risberg B, Walker PJ, White G. Transfemoral insertion of a bifurcated endovascular graft for aortic aneurysm repair: the first 22 patients. Cardiovascular Surgery 1995; 3: 121–128. 4. May J, White G, Yu W, Waugh RC, Stephen MS, McGahan T, Harris JP. Endoluminal grafting of aortic aneurysms: causes of failure and their prevention. Journal of Endovascular Surgery 1994; 1: 44–52. Sir,—We are grateful for the comments of Dr Baranowski and Mr Adiseshiah, and appreciate the opportunity to clarify several points. Numerous centres within the UK have preliminary experience of this technique, although it is probably true to say that only Leicester and Nottingham have a representative experience. It is certainly true that there is a definite learning curve to this procedure, but we are unaware of any data to support the assertion that mortality is reduced with increasing experience of the team. It is misleading to describe average mortality for this procedure as many of the patients in the larger series are elderly and unfit for routine conventional surgery [1–3]. It is suggested by Dr Baranowski and Mr Adiseshiah that endovascular aneurysm repair be used in those patients where open surgery is likely to result in patient mortality. It is our view that this is precisely the case in which endovascular surgery should be avoided until the learning curve of the procedure has been overcome and conversion to open operation occurs in a low percentage of patients. It is well documented in the literature that conversion during endovascular aneurysm repair results in a high mortality rare. If a failure to deploy the endograft appropriately is occurring in up to 35 % of cases, it may be appropriate to re-think the indications for endovascular repair in this group of patients. At present we feel that a randomized, controlled trial is required to examine procedural morbidity and mortality in patients suitable for both conventional and endovascular aneurysm repair. It must be determined if endovascular aneurysm repair is a safe procedure in “healthy” patients before its use can be advocated routinely in patients unsuitable for conventional transperitoneal surgery. We were interested to learn that the group at UCL uses significant procedural hypotension during deployment of the aortic stent. During deployment of a balloon expandable stent in our centre, we regard a mean arterial pressure of 70 mm Hg to be adequate. M. M. THOMPSON J. GREIFF Faculty of Medicine Univeristy of Leicester Leicester 1. May J, White GH, Yu W. Endoluminal grafting of abdominal aortic aneurysms: causes of failure and their prevention. Journal of Endovascular Surgery 1994; 1: 44–52. 2. Marin ML, Veith FJ, Cynamon J. Initial experience with transluminally placed endovascular grafts for the treatment of complex vascular lesions. Annals of Surgery 1995; 222: 449–469. 3. Parodi JC. Endovascular repair of abdominal aortic aneurysms and other arterial lesions. Journal of Vascular Surgery 1995; 21: 549–555.

Suxamethonium in children Sir,—The importance of recognizing subclinical myopathies in patients undergoing general anaesthesia was demonstrated clearly

883 many years ago [1] and has been stressed recently in the editorial by Hopkins [2]. When the problem of anaesthesia-induced rhabdomyolysis (AIR) is examined retrospectively, a surprising finding is that many clinical reports (including the most recent ones) lack preoperative evaluation of serum creatine kinase (CK) activity. This indicates that our attention to the problem is either poor or frustrated by the knowledge that serum CK activity is not invariably correlated with the presence or absence of myopathic conditions. The long preclinical phase of many dystrophinopathies, which are frequently involved in AIR [3], may be easily recognized or suspected on the basis of CK activity. In our experience, a definite decrease in postoperative serum CK activity may be expected in the majority of these patients if they receive general anaesthesia without the use of suxamethonium [4]. In rare circumstances, however, a life-threatening AIR may be observed even though suxamethonium has been avoided [5]. Whether or not these accidents define a particular subpopulation of dystrophinopathic patients or a particular pharmaco-metabolic condition caused by general anaesthesia is unknown. In our opinion, a poorly investigated problem is the metabolic derangement which might occur when the normal activity of the enzyme carnitine-palmitoyl-transferase is simultaneously stressed by increased lipolysis and by anaesthetic agents [6]. Preoperative fasting, anxiety and restlessness could be important in this regard. F. FIACCHINO F. CONSONNI A. DULCAMARA L. GRANDI Divisione di Neuroanestesia-Rianimazione Istituto Neurologico C. Besta Milano, Italy 1. Bennike KA, Jarnum S. Myoglobinuria with acute renal failure possibly induced by suxamethonium. A case report. British Journal of Anaesthesia 1964; 36: 730–736. 2. Hopkins PM. Use of suxamethonium in children. British Journal of Anaesthesia 1995; 75: 675–677. 3. Farrel PT. Anaesthesia-induced rhabdomyolysis causing cardiac arrest: case report and review of anaesthesia and dystrophinopathies. Anaesthesia and Intensive Care 1994; 22: 597–601. 4. Fiacchino F, Bricchi M, Gemma M, Regi B, Montolivo M, Crippa MT, Ferrazza C, Bruzzone E. Pre- and postoperative serum CK activity in 142 children submitted to “uneventful” anaesthesia for diagnostic muscle biopsy. Minerva Anestesiologica 1989; 55: 11–19. 5. Fiacchino F, Bricchi M, Balestrini MR, Ferrazza C, Montolivo M, Daniel S, Morandi L, Ariano C. Anaesthesiological rhabdomyolysis in muscular dystrophy. Minerva Anestesiologica 1984; 50: 521–526. 6. Zierz S, Schmitt U. Inhibition of carnitine palmitoyltransferase by malonyl-coA in human muscle is influenced by anesthesia. Anesthesiology 1989; 70: 373.

Sir,—Hopkins’ editorial [1] correctly asserts the advantages of suxamethonium but has not detailed the contraindications. There is evidence that it is the dystrophinopathies that account for the unexpected cardiac arrests that occur with suxamethonium [2]. The difficulty in clinical practice is to distinguish the mild, often subclinical, forms of dystrophinopathy, such as Becker’s, from normal patients. There may be no family history, and a specific history of muscle cramps with normal exercise, especially in males, may be the only clue to the underlying disorder. Hopkins’ observation that cardiac arrest occurred after inhalation induction and suxamethonium is very important, particularly as cardiac arrest has occurred after halothane and isoflurane, without suxamethonium, in patients with dystrophinopathies [3, 4]. On the basis of this evidence I believe the following recommendations can be made: (1) suxamethonium and the volatile anaesthetics are contraindicated in patients with known or suspected dystrophinopathies; (2) the use of suxamethonium should be limited to specific indications, especially in children; and (3) suxamethonium should be avoided after inhalation induction. Mortality from anaesthesia is very low. A further reduction

884 requires attention to the less frequent but known causes. Adhering to the above guidelines may help. P. T. FARRELL Department of Anaesthesia and Intensive Care John Hunter Hospital Newcastle NSW, Australia 1. Hopkins PM. Use of suxamethonium in children. British Journal of Anaesthesia 1995; 75: 675–677. 2. Farrell PT. Anaesthesia-induced rhabdomyolysis causing cardiac arrest: Case report and review of anaesthesia and the dystrophinopathies. Anaesthesia and Intensive Care 1994; 22: 597–601. 3. Rubiano R, Chang J-L, Carroll J, Sonbolian N, Larson CE. Acute rhabdomyolysis following halothane anesthesia without succinylcholine. Anesthesiology 1987; 67: 856–857. 4. Chalkiadis GA, Branch KG. Cardiac arrest after isoflurane anaesthesia in a patient with Duchenne’s muscular dystrophy. Anaesthesia 1990; 45: 22–25. Sir,—Fiacchino and colleagues appear to be advocating routine preoperative screening of creatine kinase (CK) activity and yet they observe that the sensitivity and specificity of this investigation for detecting subclinical myopathies is low. Given that the prevalence of myopathies in the population is low, the predictive value of estimating CK activity renders this an unhelpful screening test. If there are clinical features suggestive of myopathy, or there is a family history of such a condition, CK estimation may form part of the investigative process of the underlying condition, but a normal CK result does not exclude a myopathy and will not, therefore, influence short-term anaesthetic management. I am sympathetic towards Farrell’s views, but before concurring with such rigid and generalized recommendations, it is important to be sure that the necessary alternative techniques are likely to be safer in all situations. I believe that first, we should distinguish between those cases where the diagnosis of a myopathy has been made, or seems likely on the basis of clinical information, and those cases where the likelihood of a myopathy is low (no family history or clinical features). In the former group, it is generally accepted that the incidence and severity of complications attributable to suxamethonium (myotonia, postoperative ventilatory failure [1] and rhabdomyolysis) is so high as to outweigh the potential advantages of suxamethonium. When we consider the choice of maintenance drugs for general anaesthesia in these patients, the situation is not as clear. Hypermetabolic reactions and sudden massive rhabdomyolysis have been reported in dystrophic patients anaesthetized with volatile drugs without suxamethonium, but similar responses can occur in myopathic patients receiving total i.v. anaesthesia [2]. However, I believe that volatile anaesthetics do contribute directly to rhabdomyolysis [3, 4]. These disadvantages of volatile drugs need to be weighed against the detrimental cardiovascular effects of i.v, agents in patients who may have a severe cardiomyopathy. Symptoms of heart failure in patients with Duchenne dystrophy are deceivingly uncommon because of the enforced sedentary existence but myocardial dysfunction is common, as is evident from echocardiographic studies [5], which themselves can fail to detect patients with significant ventricular dysfunction [6]. One should also not ignore that there is, albeit anecdotal, great experience of the safe use of halothane in Duchenne patients. As I hoped was clear from my editorial [7], the overall incidence of cardiac arrest after suxamethonium is low, but by being meticulous in our preoperative assessment of children it is likely that we can further reduce this incidence. What we cannot quantify are the potential advantages of techniques using suxamethonium. There are no published studies that have adequately compared outcome with these and alternative techniques. Again, as argued in the editorial, such studies would need to be extremely large to achieve sufficient power to detect small, but clinically important differences. Neither are there likely to be published case reports of morbidity or mortality associated with failure to rapidly establish a secure airway when suxamethonium was not used. There will always be a risk with anaesthesia. For some individuals the risk varies according to the technique/drugs used, but there are many factors that can influence relative risk. It is my view, therefore, that rather than rely on rigid dictates, the anaesthetist must tailor the approach to clinical management to

British Journal of Anaesthesia the needs of the individual patient if anaesthetic mortality is to be minimized. This requires anaesthetists to be able physicians, trained to a high level of competence in a range of anaesthetic techniques. It also requires anaesthesia to be a strong academic discipline with practitioners motivated to establish the many strands of evidence required for objective clinical decision making, and with the ability to evaluate these in conjunction with other, often conflicting, priorities. In the absence of firm evidence, clinicians can only guess which approach, in their hands, is most likely to provide the best outcome for the patient: this is what we term “clinical judgement”. One aim of my editorial was to highlight that, until we can quantify the complete risk/benefit profile for suxamethonium, its use in children must remain a matter of clinical judgement. P. M. HOPKINS Academic Unit of Anaesthesia St James’s University Hospital Leeds 1. Smith CL, Bush GH. Anaesthesia and progressive muscular dystrophy. British Journal of Anaesthesia 1985; 57: 1113–1118. 2. Hopkins PM, Ellis FR, Halsall PJ. Hypermetabolism in arthrogryphosis multiplex congenita. Anaesthesia 1991; 46: 374–375. 3. Hopkins PM. A quantitative in vitro animal model of suxamethonium- and halothane-induced muscle damage. British Journal of Anaesthesia 1992; 68: 447P–448P. 4. Hopkins PM. The effects of caffeine and halothane on the [Ca2+]i of skeletal muscle in the absence and presence of extracellular calcium. Journal of Physiology (London) 1993; 459: 14P. 5. Goldberg S, Stern L, Feldman L. Serial two-dimensional echocardiography in Duchenne muscular dystrophy. Neurology 1982; 10: 1101–1105. 6. Sethna SF, Rockoff MA, Worthen HM, Rosnow JM. Anesthesia-related complications in children with Duchenne muscular dystrophy. Anesthesiology 1988; 68: 462–465. 7. Hopkins PM. Use of suxamethonium in children. British Journal of Anaesthesia 1995; 75: 675–677.

Isolated forearm technique Sir,—In reply to our original letter [1], Healy and Pomfrett [2] chastise us on several counts: that nitrous oxide-oxygen anaesthesia “represents a very specific anaesthetic scenario”, that we did not “allay public fears in a public forum” and that the isolated forearm technique (IFT) does not work. The first implies that nitrous oxide and opioid “anaesthesia” is a little-used, obscure technique, and thus attempts to undermine the significance of the finding that 44 % of patients are sufficiently aware to respond to command. Older readers will not need reminding that up until the late 1980s, nitrous oxide–opioid techniques were used commonly in the UK and an MDU anaesthetic adviser was prompted to discourage their use [3]. However, such techniques are still popular in continental Europe [4] and furthermore, studies using these methods continue to appear in reputable anaesthetic journals [5, 6]. Had the IFT been used more widely in the 1980s, British anaesthetists would have been aware much sooner as to how lightly “anaesthetized” their patients were. With regard to allaying public fears, the authors were interviewed, both individually and together, for various local, national and international radio and regional television networks. During these interviews it was made clear that in the UK today these anaesthetic techniques are used much less commonly than in the past. The single case of IFT failure [7] which Healy and Pomfrett make so much of occurred during Russell’s first study of the IFT when some of the technicalities were still being evaluated, and is only one of many hundreds of successful uses of the procedure. This compares well with technical failure rates of common electronic monitoring devices as a result of poor electrode contact–positioning or diathermy interference. Healy and Pomfrett suggest that because decerebrate rats show responses to surgical stimuli this invalidates the IFT. Nothing could be further from the truth. The possibility of such subcortical responses in humans is the sine qua non behind the necessity of ascertaining correctly the type of response occuring with the IFT, for example asking the patient to make conditional responses.

Correspondence Merely recording that the hand appeared to move is insufficient. Unfortunately, such unverified responses were used in the principal article quoted by Healy and Pomfrett to suggest that the IFT does not work [8]. Bogod and colleagues [8] used the IFT for the first 30 min of surgery and scored their responses as “nothing, non-specific or firm clenching/flexing”. They made no attempt to communicate with the patient. They used a command which asked the patient to open and close her hand if she could hear the message and would rather be more deeply asleep. Bogod and colleagues also classified their patients on the basis of dreams into light and deep groups and assumed that the IFT responses should bear some relationship to this split. Neither of the two patients reported as being aware [8] showed type-two responses (clenching–flexing responses) but there are major problems in interpreting these data as evidence of intraoperative awareness and failure of the IFT. Patients may not have wished to be more deeply asleep or, as the tape was not personalized with a name, the patients may not have realized the message was intended for them. More importantly, the IFT was used for only 30 min so both experiences (one described discomfort similar to a previous Caesarean section, the other a suffocating feeling) could easily have occurred after this period, particularly during the waking up and extubation period. It is true that ketamine is believed to disrupt cognitive function, but unlike thiopentone it also provides analgesia. Although the suggestion of Healy and Pomfrett that patients receiving ketamine do not respond to commands because they are conscious with impaired cognition is a possible explanation, it is much more likely that compared with thiopentone, patients who received ketamine were adequately anaesthetized [9]. Sometimes patients respond to a simple command, but do not respond appropriately to more complex commands. While such simple movements in respond to commands might not be a taxing test of cognitive function in the true psychological sense, we do not believe many anaesthetists would be likely to continue surgery without changes to their anaesthetic regimen when they observe a patient squeezing their fingers to a simple command or opening their eyes to command. In view of the data presented [10, 11], we accept that provided a volatile agent is used appropriately the majority of patients are unconscious during general anaesthesia, but such proof can only be provided by use of the IFT. There is no electronic monitor available which can give real-time quantification of depth of anaesthesia and in its absence we remain firmly of the view that the IFT is the only currently available, real-time, practical method of determining levels of consciousness during general anaesthesia involving neuromuscular block. I. F. RUSSELL Department of Anaesthesia Hull Royal Infirmary Kingston upon Hull M. WANG Clinical Psychology Unit University of Hull Kingston upon Hull 1. Russell IF, Wang M. Intraoperative awareness and the isolated forearm technique. British Journal of Anaesthesia 1995; 75: 819–820. 2. Healy TEJ, Pomfrett CJD. Intraoperative awareness and the isolated forearm technique. British Journal of Anaesthesia 1995; 75: 820–821. 3. Hargrove RL. Awareness under anaesthesia. Journal of the Medical Defence Union 1987; 3: 9–11. 4. Bonke B, Jelicic M, Bonebakker AE, De Roode A, Bovill JG. Information processing under anaesthesia. Anaesthesia 1993; 48: 820–821. 5. Head-Rapson AG, Devlin JC, Parker CJR, Hunter JM. Pharmacokinetics and pharmacodynamics of the three isomers of mivacurium in health, in end-stage renal failure and in patients with impaired renal function. British Journal of Anaesthesia 1995; 75: 31–36. 6. Slavov V, Khalil M, Merle JC, Agostini MM, Rugier R, Duvaldestin P. Comparison of duration of neuromuscular blocking effects of atracurium and vecuronium in young and elderly patients. British Journal of Anaesthesia 1995; 74: 709–711. 7. Russell IF. Auditory perception under anaesthesia. Anaesthesia 1979; 34: 211.

885 8. Bogod DG, Orton JK, Yau HM, Oh TE. Detecting awareness during general anaesthetic section. An evaluation of two methods. Anaesthesia 1990; 45; 279–284. 9. Baraka A, Louis F, Noueihid R, Diab M, Dabbous A, Sibai A. Awareness following different techniques of general anaesthesia for Caesarean section. British Journal of Anaesthesia 1989; 62: 645–648. 10. Wang M, Russell IF. Skin conductance as a measure of anaesthetic depth: typical profile and relation to isolated forearm responses. In: Proceedings of the Third International Symposium on Memory and Awareness in Anaesthesia, Rotterdam, June 8–10, 1995 (in press). 11. Russell IF, Wang M. Implicit and explicit memory for intraoperative word stimuli presented in the absence of isolated forearm responses. In: Proceedings of the Third International Symposium on Memory and Awareness in Anaesthesia, Rotterdam, June 8–10, 1995 (in press). Sir,—Thank you again for allowing us to answer yet another of Dr Wang and Dr Russell’s letters. Our original letter [1] to The Times sought not to chastise these researchers, but rather to temper the conclusions drawn from the original article by a correspondent for The Times during April, 1995 [2], which contained the sensational statement that “half of the patients on every operating list show evidence of wakefulness”. It is unfortunate that, despite their reported attempts to allay public anxiety in the media, Drs Wang and Russell did not also choose to write to The Times. We would then have seen their clarification of the facts, and would not have written any further letters on this subject. Our statement [3] that opioid anaesthesia “represents a very specific anaesthetic scenario” was not meant to infer that it is a little-used, obscure technique. It was mentioned only because the original article [2] in The Times did not mention the anaesthetic technique used, and its title inferred that half of all patients are awake during all anaesthetic procedures. We are glad to note that Drs Wang and Russell agree with us that this is not the case with appropriate levels of other anaesthetics. It is sad that they chose not to reassure readers of The Times about the outstanding efficacy of anaesthesia. It is interesting to note that the failures of the IFT reported in the literature, on which we based our statement “the IFT has been proved to be ineffective,” were all, according to Drs Wang and Russell, caused by methodological flaws. Our previous letter [3] discussed the findings of the groups who described the IFT to be ineffective in some detail, and we shall not repeat that discussion here. If we attempt to attribute something useful to this series of letters, at least they may serve to place the IFT into its proper context. The IFT is, at present, an adjunct to other anaesthetic research. One example of such research [4] used a carefully constructed procedure to define recovery of consciousness in 20 patients after a single dose of thiopentone. The patients were monitored using the IFT and a commercially available EEG monitor (Aspect A-1000). An initial orientating command (“squeeze my fingers”) was repeated every 30 s and followed, after a positive response, with a more complex test of cognition (“squeeze my fingers twice”). Only a response to the second condition was taken as proof of recovery of consciousness. This research suggested that the EEG monitor indicated consciousness at least as effectively as the IFT, but with the addition of a continuous, automatic and objective scale (bispectral index). However, neither the IFT nor the bispectral index answer what the anaesthetist really needs to know, that is what is the absolute depth of anaesthesia and is this sufficient to prevent various stimuli during surgery from causing the patient to awaken? As such a monitor, the IFT is ineffective. After all, it is too late if the patient is already awake. That is failure. T. E. J. HEALY C. J. D. POMFRETT University Department of Anaesthesia University of Manchester Manchester 1. Healy TEJ, Pomfrett CJD. Patients who remain awake during surgical operations. The Times April 18, 1995. 2. Laurance J, Half of patients “awake during surgery.” The Times April 5, 1995. 3. Healy TEJ, Pomfrett CJD. Intra-operative awareness and the

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isolated forearm technique. British Journal of Anaesthesia 1995; 75: 820–821. 4. Flashon R, Sebel PS, Singl J. Detection of consciousness following thiopental: Isolated forearm and bispectral EEG (BIS). In: Proceedings of the Third International Symposium on Memory and Awareness in Anaesthesia, Rotterdam, June 8–10, 1995 (in press).

CSF progesterone concentrations in pregnancy Sir,—I read with interest the article by Hirabayashi and colleagues [1] in which the authors showed that there was an increase in CSF progesterone concentrations in pregnancy and a greater cephalad spread of anaesthesia as pregnancy progressed. They were unable to demonstrate any correlation between CSF progesterone concentration and maximum cephalad spread of anaesthesia in any of the groups. However, they claimed that the data suggested that “not only a minimum level of progesterone in CSF but also a certain duration of exposure to elevated CSF progesterone concentrations may be necessary for enhancement of spread of spinal anaesthesia…”. Even though they were unable to show a relationship, they seem to want the reader to conclude that progesterone may be related in some way to the higher spread of spinal anaesthesia. They are suggesting causality without any evidence to support it. All patients had subarachnoid injection of hyperbaric solution which would tend to spread cephalad because of the natural curvature of the spine. One way to avoid the effect of “mechanical factors” on cephalad spread would have been to use an isobaric solution for injection. Spread of isobaric solution is not affected by the position of the patient and other mechanical factors to the same extent as a hyperbaric solution. The authors have cited several references which support the increased susceptibility of nerve tissue to block by local anaesthetic agents in pregnancy. Mechanisms which have been implicated are the direct effect of progesterone on membrane excitability, indirect actions of neurotransmitters, increased permeability of the neural sheath and potentiation of the analgesic effect of endogenous opioids. These studies can be used to explain an increase in the intensity of subarachnoid block with lignocaine but the references cited cannot explain an increase in cephalad spread of the block. N. BALIGA Department of Anesthesiology University of Michigan Medical Center Ann Arbor, MI, USA 1. Hirabayashi Y, Shimizu R, Saitoh K, Fukuda H. Cerebrospinal fluid progesterone in pregnant women. British Journal of Anaesthesia 1995; 75: 683–687. Sir,—In our article we demonstrated a time lag between an increase in CSF progesterone concentration and development of enhanced spread of spinal anaesthesia. In addition, enhanced cephalad spread of spinal anaesthesia was found to take place during the middle stage of pregnancy, in spite of its low CSF progesterone concentration. Hence, we concluded that not only a minimum level of progesterone in CSF but also a certain duration of exposure to elevated CSF progesterone concentrations may be necessary for enhanced spread of spinal anaesthesia. Because mechanical factors are insufficient to explain enhanced spread of spinal anaesthesia beginning at the middle stage of pregnancy, an increase in progesterone, as a non-mechanical factor, is expected to play an important role in the enhancement. In addition, our results showed that there was no significant correlation between CSF progesterone concentration and cephalad spread of spinal anaesthesia at any stage of pregnancy, and that cephalad spread did not differ between singletone and twin pregnancies in spite of significantly higher concentrations in CSF progesterone in parturients with twin pregnancies compared with those with singletons. From these data we concluded that the value of CSF progesterone concentration does not correlate directly with the degree of enhancement. This conclusion, however, does not deny involvement of progesterone with pregnancy-induced enhancement of spinal anaesthesia. We presume that a certain duration of exposure to elevated CSF progesterone concentrations causes enhancement of spinal anaesthesia beginning at the middle stage

of pregnancy, regardless of the values of CSF progesterone concentration. We agree with Dr Baliga’s suggestion that to avoid the effect of “mechanical factors” on cephalad spread, isobaric anaesthetic solutions are preferable to hyperbaric. Unfortunately, we do not have our own data on cephalad spread with isobaric solution, particularly with respect to pregnant women [1]. On the other hand, Russell and Holmqvist [2] compared the effects of isobaric with those of hyperbaric bupivacaine in parturients undergoing Caesarean section, and suggested that pregnancy enhances the spread of isobaric more than the spread of hyperbaric bupivacaine. Nonetheless, it remains unclear if pregnancy during the early and middle stages enhances the spread of isobaric anaesthetics. A hyperbaric solution injected into the mid-lumbar subarachnoid space spreads in both cephalad and caudal directions under the influence of gravity. In a cephalad direction, it pools in the lowest part of the thoracic hollow and then diffuses towards cephalad. The concentration of the anaesthetic agent in CSF at the cephalad part of the hollow should be lower than that at the bottom of the hollow. In this condition, a certain concentration that is devoid of local anaesthetic activity in non-pregnant women may cause conduction block in pregnant women who have an increased susceptibility of nerve tissue, resulting in an increase in cephalad spread of block. Thus increased susceptibility of nerve tissue during pregnancy may explain not only the increase in intensity of subarachnoid block but also the increase in cephalad spread of the block. The references cited in our article support the increased susceptibility of nerve tissue to block by local anaesthetics during pregnancy. The cellular mechanism of this effect, however, is not yet clear. Y. HIRABAYASHI R. SHIMIZU K. SAITOH H. FUKUDA Department of Anaesthesiology Jichi Medical School Tochigi, Japan 1. Hirabayashi Y, Shimizu R, Saitoh K, Fukuda H. Subarachnoid spread of isobaric tetracaine in adolescents. British Journal of Anaesthesia 1995; 75: 245–246. 2. Russell IF, Holmqvist LEO. Subarachnoid analgesia for Caesarean section. A double-blind comparison of plain and hyperbaric 0.5 % bupivacaine. British Journal of Anaesthesia 1989; 59: 347–353.

Extradural analgesia in the first stage of labour Sir,—We read with interest the article by Buggy and MacDowell [1] comparing an extradural mixture of clonidine and fentanyl with 0.25 % bupivacaine for the first stage of labour and wish to raise the following points. (1) While claiming that the power of the study was too low to detect a true difference in sedation scores (30 % power) and the incidence of hypotension (45 % power) between the groups, the authors conveniently omitted details of the study’s power to detect a difference in analgesic efficacy between the two groups, one of the stated aims of their study. The degree of analgesia, as assessed by visual analogue scores, was said to be similar in both groups, but considering there were only 14 patients in each group, we suspect that the study lacked sufficient power to reveal any difference. (2) Although the design of the study was said to be doubleblind, we believe that the anaesthetist performing the assessments in both groups could not have been truly blinded as to which drug regimen was being used. As the data revealed that eight patients in the 0.25 % bupivacaine group, not unexpectedly, developed significant leg weakness, presumably the anaesthetist could not have asked patients in this group to perform a Romberg’s test! (3) The authors found a median sensory level of T10 in both groups, but stated that all patients in the clonidine–fentanyl group had “preserved pinprick and temperature sensation”. Are both findings compatible? Perhaps other, unspecified, sensory tests were performed. (4) The authors stated that overall satisfaction with extradural analgesia after delivery was high in both groups: 79 % and 86 % in the clonidine–fentanyl and bupivacaine groups, respectively. The implication is that the clonidine–fentanyl mixture provided

Correspondence good analgesia overall. However, the single dose of clonidine– fentanyl used in group 1 provided analgesia only for a mean of 80 min during a much longer labour (median duration 6.4 h). Both groups subsequently received extradural infusions of 0.1 % bupivacaine in addition to further top-ups of 0.25 % bupivacaine if analgesia was inadequate. There is also no mention of the additional amounts of 0.25 % bupivacaine used in both groups. The implied overall satisfaction with the clonidine–fentanyl mixture must therefore be regarded with scepticism. (5) The authors stated in conclusion that it may be safer for patients receiving clonidine–fentanyl mixtures to walk during labour compared with a group receiving an ambulatory regimen of 0.1 % bupivacaine with fentanyl 2 ␮g ml91 because of reduced dorsal column impairment. However, it is unclear how many individual patients had abnormal dorsal column signs in the clonidine–fentanyl group. For example, did the four patients with impaired proprioception also have impaired vibration sense (n : 2) and a positive Romberg’s sign (n : 2)? Otherwise eight different patients (55 %) could have exhibited abnormal dorsal column signs, precluding ambulation. (6) Finally, neonatal assessment in the study was inadequate. Umbilical cord blood-gas values and possibly neurobehavioural scoring would have provided additional information on neonatal condition. R. FERNANDO M. G. PARRY Department of Anaesthesia Royal Free Hospital London 1. Buggy DJ, MacDowell C. Extradural analgesia with clonidine and fentanyl compared with 0.25 % bupivacaine in the first stage of labour. British Journal of Anaesthesia 1996; 76: 319–321. Sir,—We thank Drs Fernando and Parry for their interest in our article and respond to their comments sequentially. (1) Assuming that a reduction of 4 cm on the visual analogue scale (VAS) is a clinically significant reduction in pain intensity, and given a median interquartile range of 2.5 cm on the VAS from all our pain data, the power of our study to detect true differences in VAS scores was 82 %, for an alpha error of 0.05 and n : 14 in each group. The reason for our study’s apparent greater power to detect differences in pain scores compared with its relatively low power to detect differences in the incidences of side effects lies in the nature of the data: much greater power is required to detect differences in proportions between groups than for differences in data on an ordinal scale, especially when, as pointed out in our study, the incidence of these side effects was low (2) Our hospital pharmacist ensured that our study was doubleblind, using coded, labelled syringes. The table in our article indicated MRC
3, which may have been misleading. Motor weakness was taken as an MRC grade less than or equal to 3, and seven of the eight patients in this category were in fact MRC grade 3. All eight patients were able to stand and undertake Romberg’s test, although it was deemed abnormal in six. (3) Sensory level was obtained using a cold ethyl chloride spray, whereas dermatomal sensation was tested with the base of the tuning fork, in addition to pinprick. (4) All patients received an infusion of 0.1 % bupivacaine after a mean duration of 80 min on the test solutions alone, and although there were no statistically significant differences between the median amounts of bupivacaine infused, there is no doubt that overall patient satisfaction would have been influenced by the analgesia provided by this infusion. (5) The presence of posterior column signs does not preclude ambulation, as the experience of the Queen Charlotte’s group has demonstrated. We suggest a potential for greater safety in the reduction of these transient abnormalities, if the regimen can be shown in future studies to be effective and safe over a longer duration of labour. One patient in our clonidine–fentanyl group had impaired vibration sense alone, otherwise our patients with impaired proprioception also had other posterior column signs. (6) We accept that umbilical cord gases and neurobehavioural scores would indeed have provided additional information on neonatal condition. D. BUGGY C. MACDOWELL Beaumont Hospital Dublin, Ireland

887 Extradurals and infection Sir,—We read with interest the article by Jakobsen, Christensen and Carlsson [1] on extradural anaesthesia in the presence of infection. Following a case at St Helier Hospital, where there was microbiological evidence of infection in a patient receiving a continuous extradural infusion for postoperative pain relief, we undertook a survey to culture the tips from all non-obstetric catheters used for postoperative pain relief. During the first 6 months, all catheters were inserted with an aseptic nonstandardized technique, and during the second 6 months the catheters were inserted with a standardized technique. The total number of catheters inserted was 136. The overall incidence of contaminated catheters was 19.8 %. There was no significant difference in the incidence of contamination between the two techniques. There was no significant difference in the duration of the period in situ between those with a positive culture (mean 72 h) and those with a negative culture (mean 81.7 h). Specific organisms cultured included Staphylococcus epidermidis (most common), Coliform, Bacillus, Enterococcus and Diphtheroid. Except for the septicaemia seen in the patient described, we saw no other infective complications. Infected extradural catheters carry a serious risk of morbidity and mortality in terms of septicaemia, meningitis and abscess formation. In a review of the literature, we found 34 reported cases of extradural abscess [2–7] and six cases of meningitis [6, 8–14]. There were no reported cases of septicaemia. Intuitively we would expect the longer an extradural catheter is in situ the more likely the patient is to suffer infective complications, in a manner similar to indwelling i.v. catheters. However, this does not seem to be the case from our results or from a study by DuPenn and colleagues [15]. We were, however, surprised by the duration the authors left their catheters in situ, as Bromage [16] recommends that catheters should be changed every 72 h to prevent the occurrence of local tissue reactions. In view of our results, we feel that the use of indwelling extradural catheters in the management of patients who require repeated surgical procedures in the presence of infection cannot be justified as the benefits have not been shown to exceed the risks. C. M. BROSNAN St George’s Hospital London M. L. B. WOOD Queen Alexandra Hospital Portsmouth M. WHEILDON St Helier Hospital Carshalton, Surrey 1. Jakobsen KB, Christensen M-K, Carlsson PS. Extradural anaesthesia for repeated surgical treatment in the presence of infection. British Journal of Anaesthesia 1995; 75: 536–540. 2. Nigan Kee WD, Jones MR, Thomas P, Worth RJ. Extradural abscess complicating extradural anaesthesia for Caesarean section. British Journal of Anaesthesia 1992; 69: 647–652. 3. Bollenson E, Prange HW. An epidural spinal abscess as a lethal complication of peridural anaesthetic. Regional Anaesthesia 1991; 14: 101–103. 4. Ericsson M, Algers G, Schliamjer SE. Spinal epidural abscesses in adults: review and report of iatrogenic cases. Scandinavian Journal of Infectious Diseases 1990; 22: 249–257. 5. Kobayashi Y, Shiotani M, Osetok, Naganuma Y, Karasawa H. Six cases of epidural abscess probably caused by epidural block and examination by gadolinium MRI imaging. Japanese Journal of Anaesthesiology 1993; 42: 888–892. 6. Linneman MV, Bulow HH. Infections after insertion of epidural catheters. Vgeskrift for Laeger 1993; 155: 2350–2352. 7. Manourian AC, Dickman AC, Drager BP, Sonntag VK. Spinal epidural abscess: 3 cases following spinal epidural injection demonstrated with M.R.I. Anesthesiology 1993; 78: 204–207. 8. Shintani S, Tanaka H, Iriruni A, Mitoh Y, Udono H, Kaneda A, Shiigai T. Iatrogenic acute spinal abscess with septic meningitis, M.R. findings. Clinical Neurology and Neurosurgery 1992; 94: 253–255. 9. Berga S, Trierweiler MW. Bacterial meningitis following epidural anesthetic for vaginal delivery. A case report. Obstetrics and Gynecology 1989; 74: 437–439.

888 10. Davis L, Hargreaves C, Robinson PN. Postpartum meningitis. Anaesthesia 1993; 48: 788–789. 11. James FM, Geurse RH, Naiem H, White GJ. Bacteriologic aspects of epidural analgesia. Anesthesia and Analgesia 1976; 55: 187–190. 12. Barrets RS. Bacteriological culture of indwelling epidural catheters. Anesthesiology 1962; 23: 643–646. 13. Hunt JR, Rigor BM, Collins JR. The potential for contamination of continuous epidural catheters. Anesthesia and Analgesia 1973; 56: 222–225. 14. Ready LB, Helper D. Bacterial meningitis in parturients after epidural anesthesia. Anesthesiology 1989; 71: 988–990. 15. DuPenn SL, Petersson DG, Williams A, Bogosian AJ. Infection during chronic epidural catheterisation: diagnosis and treatment. Anesthesiology 1990; 73: 905–907. 16. Bromage PR. Epidural Analgesia. Philadelphia: WB Saunders Co, 1978.

Cervical haematoma and airway obstruction Sir,—We are grateful to Munro, Makin and Reid [1] for their report on cases of airway obstruction after carotid surgery. We have encountered similar problems after anterior cervical spine surgery. We agree with the authors that early intervention is to be encouraged and that deterioration of airway patency is unpredictable and can be rapid; fatalities have occurred in our hospital. The problem is that staff are reluctant to establish a tracheal airway until it is clearly necessary, because they know that the intervention may be difficult and they risk criticism of their management. Professor Eichorn has called anaesthesia a specialty with “zero tolerance for complications” [2]. Munro, Makin and Reid apologize for the use of i.v. induction and neuromuscular block in one of their cases, even though the patient’s trachea was intubated successfully. We have not found evidence in theirs or other reports [3] that i.v. induction and paralysis are less likely to be successful than inhalation induction. Airway patency nearly always deteriorates when anaesthesia is induced, for two reasons: (1) the glottic opening obstructs against the posterior pharyngeal wall as pharyngeal tone decreases [4, 5]; and (2) reflex glottic activity (coughing, breath-holding and laryngospasm). Obstruction may occur at light levels of anaesthesia in patients with upper airway pathology whatever method is used, including topical anaesthesia of the glottis [Calder, unpublished observations]. Deep general anaesthesia is required to obtund glottic reflex activity sufficiently to allow intubation. This can be difficult to obtain with an inhalation technique and may be impossible if the airway is obstructed. Our experience with halothane and spontaneous ventilation for fibreoptic tracheal intubation led us to abandon the technique. At least one patient in our series survived only because muscle paralysis and positive pressure ventilation were commenced [6]. In our experience a period of positive pressure ventilation is required to obtain sufficient glottic relaxation when halothane is used. The benefits of positive pressure, or at least CPAP, in the relief of severely obstructed airways have been mentioned by several authors [7–9], and positive pressure is the mainstay of treatment in obstructive sleep apnoea [10]. We do not seek to dissuade our colleagues from using an inhalation technique, but we suggest that it is no more likely to succeed than any other when severe airway obstruction is present. It is unhelpful to give the impression that the use of airway-friendly i.v. agents such as propofol or neuromuscular blockers may expose practitioners confronted with a desperate emergency to criticism. Our advice to practitioners treating patients with anterior cervical haematomas is: (1) be aware that complete airway obstruction can occur suddenly; (2) inhalation of nebulized adrenaline can improve the airway, but is not a substitute for securing the airway – we have had a fatality in a patient whose airway improved dramatically with adrenaline but obstructed completely some hours later; (3) have a surgeon standing by ready to perform a tracheotomy; (4) awake fibreoptic intubation in the sitting position is a good technique, but be aware that the airway can deteriorate during the procedure because of (1) above, and because lignocaine can provoke laryngospasm when applied to the glottis [11]; (5) insufflate oxygen via a nasal catheter; (6) have a laryngeal mask airway (LMA), a gum elastic bougie and also a 6.0mm diameter tube to allow through LMA intubation [12]; (7) use whatever method of induction with which you are comfortable

British Journal of Anaesthesia and give neuromuscular blockers if the patient may benefit; and (8) use a small tube (7.0-mm diameter maximum) and do not remove it for at least 24 h. Our aim should be to encourage early intervention by emphasizing that in the early stages any method is likely to be successful, and refraining from criticism if difficulty is encountered, because it is probable that pathology, not technique, is to blame. I. CALDER K. F. KOH Department of Neuroanaesthesia National Hospital for Neurology and Neurosurgery London 1. Munro FJ, Makin AP, Reid J. Airway problems after carotid endarterectomy. British Journal of Anaesthesia 1996; 76: 156–159. 2. Eichorn JE. Pulse oximetry as a standard of practice in anesthesia. Anesthesiology 1993; 66: 157–162. 3. O’Sullivan JC, Wells DG, Wells GR. Difficult airway management with neck swelling after carotid endarterectomy. Anaesthesia and Intensive Care 1986; 14: 460–464. 4. Boiden MP. Airway patency in the unconscious patient. British Journal of Anaesthesia 1985; 57: 306–310. 5. Nandi PR, Charlesworth CH, Taylor SJ, Nunn JF, Doré CJ. The effect of general anaesthesia on the pharynx. British Journal of Anaesthesia 1991; 66: 157–162. 6. Smith M, Calder I, Crockard HA, Isert P, Nicol ME. Oxygen saturation and cardiovascular changes during fibreoptic intubation under general anaesthesia. Anaesthesia 1992; 47: 158–161. 7. Sparks CJ. Ludwig’s angina causing respiratory arrest in the Solomon Islands. Anaesthesia and Intensive Care 1993; 21: 460–462. 8. Riazi J. The difficult pediatric airway. In: Benumof JL, ed. Airway Management—Principle and Practice. New York: Mosby, 1995; 585–637. 9. King CJ, Davey AJ, Chandradeva K. Emergency use of the laryngeal mask airway in severe upper airway obstruction caused by supraglottic oedema. British Journal of Anaesthesia 1995; 75: 785–786. 10. Hanning CD. Obsructive sleep apnoea. British Journal of Anaesthesia 1989; 63: 477–488. 11. Sidhu VS, Whitehead EM, Ainsworth QP, Smith M, Calder I. A technique of awake fibreoptic intubation. Experience in patients with cervical spine disease. Anaesthesia 1993; 48: 910–914. 12. Silk JM, Hill HM, Calder I. Difficult intubation and the laryngeal mask. European Journal of Anaesthesiology 1991; (Suppl. 4): 47–51.

Sir,—We thank Dr Calder and Dr Koh for their interest in our report. We appreciate that the safest and most appropriate management of a difficult airway is usually that method with which the anaesthetist feels most confident. However, regarding i.v. induction and paralysis we feel that this may not be as successful, as one or our original references indicates [1]. In a series of six cases, in the four who were paralysed, the lungs could not be ventilated by hand. Two of these patients became asystolic and two suffered bradycardia of which one was less than 10 beat min91. Of these one had an emergency tracheotomy and in the other three, the trachea was intubated blindly. The two other cases underwent inhalation induction, one after ensuring the ability to hand ventilate was paralysed, and in both the trachea was intubated with comparative ease. We agree that early intervention is to be encouraged, however, in such cases the degree of airway distortion should never be underestimated, and that a surgical airway may be a safe alternative. F. J. MUNRO A. P. MAKIN J. REID Western Infirmary Glasgow

Correspondence 1. O’Sullivan JC, Wells DG, Wells GR. Difficult airway management with neck swelling after carotid endarterectomy. Anaesthesia and Intensive Care 1986; 14: 460–464.

Management of pre-eclampsia Sir,—We read with interest the recent review article by Mushambi, Halligan and Williamson [1] on recent developments in the pathophysiology of eclampsia, and wish to draw attention to a recent case who responded dramatically to Centoxin. It raises several interesting questions and possibilities for future research and management of these patients, particularly in respect of liver damage and possible gastrointestinal failure, some aspects of which were not included in this review article. The case was a 31-yr-old primigravida who was delivered of a live infant under extradural anaesthesia by Ventouse extraction. She had had an uneventful antenatal course with no sign of pregnancy-induced hypertension, although 2;⬘ protein were recorded in the urine throughout labour. Three hours after delivery she started to complain of headaches and epigastric pains, at this time she was found to be mildly hypertensive (165/95 mm Hg). Simple analgesia and baseline investigations were ordered. Six hours after delivery she convulsed. Further episodes occurred 1 and 2 h later. While observed on the delivery ward she was given phenytoin and diazepam, but additional treatment with Heminevrin and thiopentone (at low doses) were required to control the convulsions. Unfortunately, there were no intensive care beds available at the time and so management was continued in the delivery suite. Central venous pressure was monitored and urine output (with heavy proteinuria) maintained with careful boluses of human albumin solution. The patient continued to deteriorate, becoming febrile with tachycardia, and a labile arterial pressure, and she showed signs of pulmonary oedema. Serum blood glucose concentration became unstable (reaching as low as 1.2 mmol litre91 at one time) and required supplementary glucose. Biochemical and haematological evidence of worsening multi-organ failure became evident, as her LFT became elevated and haemoglobin decreased to 8.8 g litre91 with a platelet count of 58 109 litre91. It was thought that an ensuing systemic inflammatory reaction syndrome (SIRS) was developing. It was thought unlikely that any products of conception were retained, her urine was clear of organisms and therefore perhaps significant translocation of gut bacteria and endotoxins was occurring. With deranged liver function, especially the reticuloendothelial aspect, it was possible that this was causing significant endotoxaemia. After much discussion with the intensivists it was decided to administer Centoxin (HA-1A) to this patient (she was already receiving cefuroxime and metronidazole). Within 4 h she became demonstrably more stable and less agitated. Sedation was stopped and arterial pressure became normal; blood glucose concentration became less erratic. Over the next 8 h the clinical signs of pulmonary oedema stabilized (she had demonstrable cardiomegaly on the chest x-ray) and her temperature returned to normal. All cultures failed to grow organisms. Despite persisting albuminuria, peripheral oedema stabilized over the next 24 h and blood glucose concentrations became normal. Although it could be argued that this eclamptic patient would have stabilized as rapidly without Centoxin, as she had delivered the fetal–placental unit, it does suggest that significant endotoxaemia was occurring (although we have no proof). Perhaps the phrase “toxaemia of pregnancy” should be retained? It may well be that a form of systemic inflammatory reaction is occurring in this disease as a result of the immunological insult outlined in the review article. There is limited evidence in animal models that gut translocation can contribute to the pathophysiology of eclampsia [2, 3], although little human evidence has yet been published [4]. Clearly, liver impairment contributes to endotoxaemia (and other forms of sepsis from gut organisms), and often this liver damage is neglected in pre-eclamptic and eclamptic patients until severe failure has occurred. Perhaps the “fatty liver of pregnancy” is one form of end-organ failure caused by the same pre-eclamptic process, another being the more easily recognized HELLP syndrome? In this unit we observe carefully for liver impairment and monitor blood glucose concentrations regularly. Other forms of liver support can then be given as needed for acute liver failure [5]. This aspect of end-organ damage was overlooked in the review article and we commend regular blood glucose estimation as the minimum for monitoring liver dysfunction; regular clotting

889 screen and protein–albumin concentrations should also be undertaken. Perhaps the gastrointestinal tract itself should be encompassed in the list of end-organs to fail? Another form of end-organ damage which may also be part of the pre-eclamptic disease process is that of the heart failure seen in severe eclamptics; perhaps this is part of “cardiomyopathy of pregnancy” and instituted by a similar immunological stimulus. Clearly more studies are required into the specific immunological problems and complex processes that occur in preeclampsia, but perhaps the role of endotoxins could be defined further. J. E. H. WARD J. A. CAUNT J. ALDERSON Northern General Hospital Sheffield 1. Mushambi MC, Halligan AW, Williamson K. Recent developments in the pathophysiology and management of preeclampsia. British Journal of Anaesthesia 1996; 76: 133–148. 2. Faas MM, Schuiling GA, Baller JF, Visscher CA, Bakker WW. A new animal model for human preeclampsia: ultra-lowdose endotoxin infusion in pregnant rats. American Journal of Obstetrics and Gynecology 1994; 171: 158–164. 3. Collins JG, Smith MA, Arnold RR, Offenbecher S. Effects of Escherichia coli and Porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster. Infection and Immunology 1994; 62: 4652–4655. 4. Laham N, Brennecke SP, Bendtzen K, Rice GE. Tumour necrosis factor alpha during human pregnancy and labour; maternal plasma and amniotic fluid concentrations and release from intrauterine tissues. European Journal of Endocrinology 1994; 131: 607–614. 5. Stanley AJ, Lee A, Haynes PC. Management of acute liver failure; aetiology, complications and management. British Journal of Intensive Care 1995; 5: 8–15.

Sir,—We thank Drs Ward, Caunt and Alderson for their interest in our review article and are grateful for their comments. We are unable to comment on their theory of endotoxaemia or the role of Centoxin, but we wish to make some points. First, Centoxin was withdrawn from use in 1993. This raises the question of why it was used, unless of course the case described occurred before 1993. We also wish to question their management of eclampsia using phenytoin, diazepam, chlormethiazole (Heminevrin) and “lowdose” thiopentone. The use of magnesium sulphate in this patient would have been a preferable choice of drug. Compared with diazepam and phenytoin, magnesium sulphate has been shown to control convulsions, reduce recurrent convulsions and cause fewer side effects [1]. The use of chlormethiazole in the treatment of eclampsia is unacceptable because of the problem of fluid overload and oversedation. Magnesium sulphate is now the drug of choice in patients with eclampsia. From the clinical signs described and laboratory findings stated, it is most likely that the above patient had HELLP syndrome, and hypoglycaemia is a known complication of this syndrome, as stated in our article [2, 3]. Pulmonary oedema in patients with pre-eclampsia results commonly from fluid overload and less frequently from left ventricular dysfunction. Unfortunately the letter does not indicate the type or amount of fluid their patient received, her urine output or central venous or pulmonary wedge pressures; these data would have been helpful in determining the cause of her pulmonary oedema. Unfortunately, pre-eclampsia is still a disease for which many theoretical and improved aetiologies abound and because it is a multisystem disorder, it has many ways of presenting. M. C. MUSHAMBI A. W. HALLIGAN K. WILLIAMSON Leicester Royal Infirmary Leicester 1. The Eclampsia Trial Collaborative Group. Which anti-

890 convulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995; 345: 1455–1463. 2. Egley CC, Guthlip JA, Bowes WA. Severe hypoglycemia associated with HELLP syndrome. American Journal of Obstetrics and Gynecology 1985; 152: 576–577.

British Journal of Anaesthesia 3. Mushambi MC, Halligan AW, Williamson K. Recent developments in the pathophysiology and management of preeclampsia. British Journal of Anaesthesia 1996; 76: 133–148.

ERRATUM British Journal of Anaesthesia 1996; 76: 284–291 p. 287. In the legend for figure 2, “……elevated initial Fa O (0.08)” should read “……elevated initial Fa CO2 (0.08)” 2

We apologize to the authors for this confusion which arose during the editorial process.