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Epidural anaesthesia for caesarean section in an achondroplastic dwarf
British Journal of Anaesthesia 82 (2): 299–308 (1999)
Correspondence Malignant hyperpyrexic syndrome Editor,—The letter to the Lancet by Denborough and Lovell in 1960 and the report of Denborough and colleagues in 1962 are, as pointed out in the commentary by Ellis,1 landmarks for the recognition of malignant hyperthermia (MH) in medical anaesthesia. However, it may be of interest that the syndrome in pigs was, in fact, first described by Hall and colleagues2 and subsequently investigated by the same group3–5 before Harrison’s publication in 1975. Gainsford Harrison visited Cambridge to discuss these investigations and it became obvious that there was a significant difference between the pigs he used (Landrace breed) and the LandraceX pigs in the UK. For example, in South Africa, the experimental condition could be set up in the pure-bred Landrace pigs after induction of general anaesthesia with thiopental whereas in the LandraceX pigs, thiopental appeared to protect from the induction of the syndrome. This led to difficulties in the detailed study of the syndrome in the UK, but indicated that genetic makeup might be implicated in its manifestation. Unfortunately, lack of funding then prevented further work in the UK. It is greatly to Harrison’s credit that he recognized the potential of dantrolene in the prevention and treatment of MH in both pigs and humans but it is perhaps a sad reflexion of our times that it took more than 5 yr before the place of this drug came to be appreciated in medical anaesthesia. Could this have been related to the cost of the drug and its relatively short shelf-life coupled with the failure of those on UK grant-awarding bodies to recognize the need to investigate the potential of this drug in saving lives? L. W. Hall Cambridge, UK 1 Ellis FR. Commentary. Br J Anaesth 1998; 81: 625 2 Hall LW, Woolf N, Bradley JWP, Jolly DW. Unusual reaction to suxamethonium chloride. BMJ 1966; ii: 1305 3 Woolf N, Hall LW, Thorne C, Down M, Walker RG. Serum creatine–phosphokinase levels in pigs reacting abnormally to halogenated anaesthetics. BMJ 1970; iii: 386–7 4 Hall LW, Trim CM, Woolf N. Further studies of porcine malignant hyperthermia. BMJ 1972; ii: 145–8 5 Bradley WG, Ward M, Murchison D, Hall LW, Woolf N. Clinical, electrophysiological and pathological studies in malignant hyperpyrexia. Proc R Soc Med 1973; 66: 67–8
Editor,—I’m pleased Dr Leslie Hall has put on record his own important contributions to our knowledge of malignant
hyperthermia (MH), especially in pigs. His description of succinylcholine-induced MH in 1966 was of course a landmark in this field, although difficult to interpret in the light of later findings. He points out the discrepancies in the pig research and this indeed highlights that there are important discrepancies between the pig syndrome and MH in humans. F. R. Ellis University of Leeds St James’s University Hospital Leeds, UK
Early clinical experience with a newly formulated hydroxyethyl starch—Hextend Editor,—We would like to report our early experience with a newly formulated hydroxyethyl starch (HES), Hextend (BioTime Inc, Berkeley, CA, USA). Currently, clinicians are re-evaluating their blood transfusion policies with both economic and safety issues driving the reduction in use of donated human blood products. Increasing surgical demands have increased the volumes of artificial colloids to which patients are exposed. New concerns about the uses of human albumin solution1 intensify the search for a ‘colloid of choice’. Hextend is a medium molecular weight HES (450 kDa) formulated with mixed electrolytes (sodium 141 mmol litre–1, chloride 124 mmol litre–1, potassium 3.0 mmol litre–1, calcium 2.55 mmol litre–1, magnesium 0.9 mmol litre–1), lactate and glucose to preserve a more ‘plasma-like’ physiological milieu than in other comparable artificial colloids. In previously presented HES solutions, the suspending medium was 0.9% saline solution with chloride 154 mmol litre–1. It is becoming apparent that our ability to tolerate a high chloride load is imperfect and that, particularly in the presence of renal compromise, such a load can lead to the development of acid–base disturbance.2 In an open label study, Hextend was administered for the first time to humans to evaluate its efficacy and safety. Five patients have so far received Hextend 500–3150 ml, administered according to a treatment algorithm. It proved to be an effective volume expander achieving the algorithm goals which triggered infusion. Changes in measured electrolytes outside normal limits were not seen in any patient. We performed detailed in vitro coagulation studies and observed predictable changes in factor VIII moieties from previous experience with HES of molecular weight 450 kDa. There were no idiosyncratic effects observed.
© British Journal of Anaesthesia
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The HES component of Hextend represents a return to higher molecular weight moieties. Lower molecular weight HES have been reported to have less effect on the coagulation system, particularly factor VIII associated proteins, although the clinical significance of this in terms of bleeding is vague.3 The prolonged intravascular persistence of a higher molecular weight HES may offer advantages in isovolaemic haemodilution which outweigh its poorly defined effect on blood coagulation in this type of application. We suggest that this agent may be a useful adjuvant to volume therapy and that further evaluation may identify the importance of physiological balance in large volume transfusion of artificial colloid. R. L. Woolf M. V. Chapman M. G. Mythen Department of Anaesthesia University College London Hospitals London, UK
additional opioids in the doses mentioned. Any differences between study groups may be too small to detect in a small number of patients. We agree with the authors1 that a clinically useful application of pre-emptive analgesia with morphine may not be possible because of the need for the return of spontaneous respiration at the end of surgery. Whether use of drugs such as remifentanil, which would allow a greater dose and antinociceptive effect during operation, will demonstrate pre-emptive analgesia remains to be seen. N. A. Randhawa P. P. Bapat Department of Anaesthetics West Middlesex University Hospital Isleworth, Middlesex, UK 1 Millar AY, Mansfield MD, Kinsella J. Influence of timing of morphine administration on postoperative pain and analgesic consumption. Br J Anaesth 1998; 81: 373–6 2 Finck AD, Samaniego E, Nagai SH. Nitrous oxide selectively releases Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 into canine third ventricular cerebrospinal fluid. Anesth Analg 1995; 80: 664–70 3 Yang JC, Clark WC, Ngai SH. Antagonism of nitrous oxide analgesia by naloxone in man. Anesthesiology 1980; 52: 424–7 4 Goto T, Marota JJ, Crosby G. Nitrous oxide induces preemptive analgesia in the rat that is antagonized by halothane. Anesthesiology 1994; 80: 409–16 5 O’Connor TC, Abram SE. Inhibition of nociception induced spinal sensitisation by anesthetic agents. Anesthesiology 1995; 82: 259–66
1 Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ 1998; 317: 235–40 2 Mathes DD, Morell RC, Rohr MS. Dilutional acidosis: is it a real clinical entity? Anesthesiology 1997; 86: 501–3 3 Treib J, Haass A, Pindur G. Influence on intravascular molecular weight of hydroxyethyl starch on platelets during a long term haemodilution. Thromb Haemost 1997; 78: 974–83
Pre-emptive analgesia—why the evidence is Editor,—We accept the possibility that the use of nitrous oxide may act as a confounding variable when looking conflicting for a pre-emptive analgesic effect using another analgesic. Editor,—We read with interest the article by Millar, Mansfield and Kinsella1 and would like to raise some points for discussion. They have given several reasons for failure to demonstrate pre-emptive analgesia in various studies. Another potential reason may be the inclusion of nitrous oxide in the design of all clinical studies. The analgesic effect of nitrous oxide is probably a result of involvement of the proenkephalin derived family of endogenous opioids.2 This finding is further supported by the fact that naloxone antagonizes the analgesic effect of nitrous oxide.3 Nitrous oxide has been shown to produce pre-emptive analgesia in rats.4 Interestingly, in the same study, it was reported that halothane antagonized the analgesic effect of nitrous oxide. However, another animal study5 showed inhibition of nociception-induced spinal sensitization by most anaesthetic agents, except halothane. Whether a similar effect occurs in humans is not known. It is not inconceivable that the use of 66% nitrous oxide has a pre-emptive effect which is not greatly improved by
However, we do not think this is a valid concern for the following reasons. First, in humans, nitrous oxide is a very weak analgesic and it is difficult to believe that it alone could prevent noxious stimuli from having an effect on the spinal cord. Second, if nitrous oxide were to have a pre-emptive influence, we might expect that those subjects anaesthetized with nitrous oxide would have reduced analgesic requirements after operation compared with those anaesthetized breathing air–oxygen mixtures. This was not noted in our clinical experience and has not been demonstrated when studied in humans.1 2 A.Y. Millar J. Kinsella Directorate of Anaesthesia Glasgow Royal Infirmary Glasgow, UK
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1 Krogh B, Jorn Jensen P, Henneberg SW, Hole P, Kronborg O. Nitrous oxide does not influence operating conditions or
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postoperative course in colonic surgery. Br J Anaesth 1994; 72: 55–7 2 Jensen AG, Prevedoros H, Kullman E, Anderberg B, Lennmarken C. Peroperative nitrous oxide does not influence recovery after laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1993; 37: 683–6
Cisatracurium in a patient with atypical plasma cholinesterase Editor,—Cisatracurium is one of the 10 stereoisomers that constitute atracurium. As with atracurium, cisatracurium undergoes spontaneous non-organ-dependent Hofmann degradation at physiological pH and temperature. Unlike atracurium, non-specific ester hydrolysis does not appear to play a significant role in the degradation of cisatracurium1–6: 80% of a dose of cisatracurium is cleared by non-organdependent Hofmann elimination. With both drugs, the liver and kidneys play only a minor role in elimination.1–5 The non-specific ester hydrolysis of atracurium is independent of plasma cholinesterase activity. In vitro experiments have shown that the rates of breakdown of atracurium are not different when the drug is incubated in normal plasma or in plasma obtained from genetically deficient homozygous patients with virtually no plasma cholinesterase activity.7 This finding has been confirmed clinically; we have shown, using electromyography, a normal response to atracurium in a homozygous patient with atypical cholinesterase activity.8 The following case report investigates the neuromuscular blocking effect of cisatracurium in a patient with atypical plasma cholinesterase activity. A 57-yr-old male, weighing 100 kg, was scheduled for nasoplasty. During previous surgery, he received succinylcholine 75 mg for tracheal intubation, which was followed by prolonged neuromuscular block lasting 7 h. Because of this history, plasma cholinesterase concentrations and dibucaine number were estimated before the present operation. Plasma cholinesterase activity was 2.3 units (normal value 2.5–4.5 units) and dibucaine number was 35, suggesting homozygote atypical plasma cholinesterase activity. The patient was premedicated with glycopyrrolate 0.2 mg i.m. and diazepam 5 mg orally. Anaesthesia was induced with propofol 2 mg kg–1, lidocaine 1 mg kg–1 and fentanyl 1.5 µg kg–1. Neuromuscular transmission was monitored using a Datex electromyograph. The ulnar nerve was stimulated supramaximally at the wrist every 20 s using the trainof-four (TOF) twitch technique at a stimulus rate of 2 Hz. A bolus dose of cisatracurium 0.15 mg kg–1 (3 3 ED95) was then given. Complete neuromuscular block was achieved after 120 s, when tracheal intubation was performed easily. Anaesthesia was maintained with 1% isoflurane and 66% nitrous oxide in oxygen. After 20 min, 25% recovery of the first twitch of the TOF was observed, and a maintenance dose of cisatracurium
0.05 mg kg–1 was given. At the end of surgery, which lasted 60 min, 50% recovery of the first twitch of the TOF was observed. Residual neuromuscular block was antagonized successfully using neostigmine 0.05 mg kg– 1 and glycopyrrolate 0.01 mg kg–1. The twitch response was restored completely, and tetanus was maintained with no post-tetanic facilitation. This report confirms that cisatracurium, in common with atracurium,8 can be used safely in patients with atypical plasma cholinesterase. A. Baraka A. Soueidi C. Berzina Department of Anesthesiology American University of Beirut Beirut, Lebanon 1 Lien CA, Schmith VD, Belmont MR, Kisor D, Savarese JJ. Pharmacokinetics/dynamics of 51W89 in patients during opioid anesthesia. Anesthesiology 1994; 81: A1090 2 Ornstein E, Lien CA, Matteo RS, et al. Pharmacodynamics and pharmacokinetics of 51W89 in geriatric surgical patients. Anesthesiology 1994; 81: A1075 3 Dewolf AM, Freeman F, Scott V, et al. Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end stage liver disease undergoing liver transplantation. Anesthesiology 1994; 81: A1075 4 Eastwood NB, Boyd AH, Parker MA, Hunter JM. Pharmacokinetics of 1R-cis 19R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure. Br J Anaesth 1995; 74: 400–4 5 Boyd AH, Eastwood NB, Parker CJR, Hunter JM. A comparison of the pharmacodynamics and pharmacokinetics of an infusion of cisatracurium (51W89) or atracurium in critically ill patients undergoing mechanical ventilation in the intensive therapy unit. Br J Anaesth 1996; 76: 382–8 6 Kisor D, Wargin WA, Schmith VD, Cook DR, Ornstein E. Organ independent elimination of 51W89. Pharmacol Res 1994; 11: S335 7 Merrett RA, Thompson CW, Webb FW. In vitro degradation of atracurium in human plasma. Br J Anaesth 1983; 55: 61–6 8 Baraka A, Abu Jaoude C. Atracurium in a parturient with atypical cholinesterase. Br J Anaesth 1984; 56: 930–1
Epidural anaesthesia for Caesarean section in an achondroplastic dwarf Editor,—We were interested to read the case report by Morrow and Black1 describing the anaesthetic management of an achondroplastic dwarf undergoing Caesarean section. As the authors stated, such patients present a significant challenge for the anaesthetist, and yet there is little information in the literature to guide effective management. Most of the published work consists of case reports and, in common with the present account, relate to anaesthesia for elective Caesarean section where time is available to
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perform central neural block using an epidural or microspinal catheter. Having recently found ourselves in a similar situation,2 we would be interested in how the authors might have managed their case for an emergency Caesarean section, when time constraints may preclude the use of an incremental technique, and yet the patient is keen to be awake for delivery. A. Ravenscroft C. Rout Department of Anaesthesia University of Natal Durban, South Africa 1 Morrow MJ, Black IH. Epidural anaesthesia for Caesarean section in an achondroplastic dwarf. Br J Anaesth 1998; 81: 619–21 2 Ravenscroft AJ, Govendor T, Rout C. Spinal anaesthesia for emergency caesarean section in an achondroplastic dwarf. Anaesthesia 1998; 53: 1236–7
Editor,—We appreciate the interest in our article1 shown by Drs Ravenscroft and Rout and are grateful for the opportunity to reply. There are few guidelines on the use of epidural or spinal anaesthesia in the gravid achondroplastic dwarf; most of the available data are derived from a small number of case reports. In one such letter, Crawford and Dutton2 reported that infusion of 0.5% hyperbaric bupivacaine 0.5 ml intrathecally resulted in bilateral block to T6 within 20 min, and that the block was associated with significant hypotension. The intra-abdominal position of the uterus in patients with achondroplasia may result in particularly severe aorto-caval compression.3–5 When this problem is compounded by the sudden onset of central neural block, there is the possibility that catastrophic hypotension may result. In a series of patients of normal stature undergoing elective Caesarean section, Robson and colleagues demonstrated that a marked decrease in cardiac output occurs after spinal anaesthesia,6 but that such a decrease is not associated with epidural anaesthesia or an incremental spinal technique.7 It is debatable whether this work is applicable to patients with achondroplasia. However, in the absence of data indicating otherwise, it would seem reasonable to assume that a similar, if not greater, reduction in cardiac output may result when rapid onset of spinal block occurs in this subgroup of patients. We considered initially the use of a ‘single-shot’ spinal technique but decided against this approach when it became apparent that the combination of factors outlined above made it potentially hazardous, particularly if general anaesthesia was required in the event of a failed spinal block. Before siting the epidural, we decided that in the event of accidental dural puncture, the operator would pass the epidural catheter into the subarachnoid space and we would perform the procedure under incremental spinal anaesthesia. Faced with a similar situation to that described
by Drs Ravenscroft and Rout, our choice would be to perform an elective dural puncture using an 18-gauge Tuohy needle, pass the catheter intrathecally and establish spinal block using a small dose of 0.5% hyperbaric bupivacaine. An initial dose of 0.3 ml, followed by 0.1 ml increments as required to achieve surgical block would be our approach. Invasive arterial pressure monitoring would be advisable. We feel that the use of intrathecal opioids should be treated with extreme caution in this situation, in view of the potential for unpredictable spread of the injectate within the cerebrospinal fluid in achondroplastic patients. The relatively small time delay involved in the use of this approach would, in our opinion, outweigh the potential risks of severe hypotension and unpredictable block height (with the consequent need for general anaesthesia) that could result from the use of a ‘single-shot’ spinal injection. We believe that the use of an incremental technique should not necessarily be ruled out in the emergency situation. The amount of time spent establishing an incremental surgical block should account for a relatively small proportion of the overall anaesthetic time spent in patient preparation and accessing the subarachnoid space, and would add to the overall safety of the procedure. Obviously, the use of such an approach would result in a higher risk of post-dural puncture headache and the use of standard guidelines aimed at minimizing its occurrence should be adopted. Should the need arise, epidural blood patching may be attempted at a later date under less stressful conditions. Adequate preparation time for any form of central neural block is fundamental to the successful outcome of the procedure, and the role of good communication between all members of the team involved in the perinatal care of this group of patients is of the utmost importance. M. J. Morrow Royal Maternity Hospital Grosvenor Road Belfast, Northern Ireland I. H. Black Antrim Area Hospital Antrim, Northern Ireland
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1 Morrow MJ, Black IH. Epidural anaesthesia for Caesarean section in an achondroplastic dwarf. Br J Anaesth 1998; 81: 619–21 2 Crawford M, Dutton DA. Spinal anaesthesia for caesarean section in an achondroplastic dwarf. Anaesthesia 1992; 47: 1007 3 Brimacombe JR, Caunt JA. Anaesthesia in a gravid achondroplastic dwarf. Anesthesia 1990; 45: 132–4 4 Cohen SE. Anaesthesia for Cesarean section in achondroplastic dwarfs. Anesthesiology 1980; 52: 264–6 5 Wardall GJ, Frame WT. Extradural anaesthesia for Caesarean section in achondroplasia. Br J Anaesth 1990; 64: 367–70 6 Robson SC, Boys RJ, Rodeck C, Morgan B. Maternal and fetal haemodynamic effects of spinal and extradural anaesthesia for elective Caesarean section. Br J Anaesth 1992; 68: 54–9
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7 Robson SC, Samsoon G, Boys RJ, Rodeck C, Morgan B. Incremental spinal anaesthesia for elective Caesarean section: maternal and fetal haemodynamic effects. Br J Anaesth 1993; 70: 634–8
Inadvertent inhalation anaesthesia during surgery under retrobulbar eye block Editor,—I read with concern Dr Smith’s case report on inadvertent inhalation anaesthesia during surgery under retrobulbar eye block.1 It is axiomatic that equipment should not be used without first being checked. It is clear that the anaesthetic machine used in the case described had not been checked before use. It is just as clear that this arose from its being used by someone other than an anaesthetist. This must be identified as the sole cause of the near fatal accident. We do not allow anyone to drive or fly without a licence. We should not allow anyone to use an anaesthetic machine except an anaesthetist. A wall mounted oxygen flow meter, such as is used routinely in recovery and ICU, should be the sole method by which non-anaesthetists are allowed to administer oxygen in theatre. I would not even allow its mounting on the anaesthetic machine, as shown in Dr Smith’s photograph. There should be no exceptions. C. P. H. Heneghan Nevill Hall Hospital Abergavenny, UK
recruited were elderly (age range 54–81 yr) and some had severe disease (ASA III), warrants comment. The authors stated that ‘short-term NSAIDs for surgical patients does not seem to induce irreversible renal failure’. However, NSAIDs are implicated in up to 15.6% of druginduced reports of acute renal failure (ARF),2 and although most patients recover with appropriate management, the relatively rare complications of papillary necrosis and interstitial nephritis can be irreversible. NSAID-induced ARF is often pre-renal. Known risk factors include old age, volume depletion from diuretics and other causes such as postoperative bleeding, congestive heart failure, diabetes mellitus and renal impairment; risk is also dose-dependent.3 For these reasons, the manufacturers of all three drugs recommend a reduction in dose when these drugs are used in the elderly. For instance, the maximum recommended dose of ketorolac is 60 mg in 24 h, which is half the dose used in this study. Indeed, the incidence of serious and fatal adverse events reported with ketorolac has decreased since revision of dosage guidelines.4 Finally, recent guidelines on the use of NSAIDs in the perioperative period advise that they should be used with caution in these conditions and that renal function should be monitored regularly in patients after major surgery.5 F. A. M. Gibson Department of Anaesthesia St Thomas’s Hospital London, UK 1 Kostamovaara PA, Hendolin H, Kokki H, Nuutinen LS. Ketorolac, diclofenac and ketoprofen are equally efficacious for pain relief after total hip replacement. Br J Anaesth 1998; 81: 369–72 2 Delmas PD. Non-steroidal anti-inflammatory drugs and renal function. Br J Rheumatol 1995; 34 (Suppl. 1): 25–8 3 Perez Gutthann S, Garcia Rodriguez LA, Raiford DS, Duque OA, Ris Romeu J. Non-steroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure. Arch Intern Med 1996; 156: 2433–9 4 Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 1997; 53: 139–88 5 Guidelines for the Use of Non-Steroidal Anti-inflammatory Drugs in the Peri-operative Period. London: Royal College of Anaesthetists, 1998
1 Smith WQ. Inadvertent inhalation anaesthesia during surgery under retrobulbar eye block. Br J Anaesth 1998; 81: 793–4
Editor,—Thank you for the opportunity to respond to Dr Heneghan’s letter. He has succinctly summarized a corollary of the conclusions in my case report: that if surgery is undertaken in the absence of an anaesthetist, then it is the operating surgeon who bears the full responsibility for the total care of that patient. While this apportions responsibility, undoubtedly it would be more appropriate for an anaesthetist to be in attendance in such circumstances. Q. Smith City Hospitals Sunderland Sunderland Royal Hospital Sunderland, UK
Reduce dose of NSAIDs in the elderly Editor,—I read with interest the article by Kostamovaara and colleagues comparing ketorolac, diclofenac and ketoprofen for pain relief after total hip surgery.1 The authors’ use of the ‘recommended maximal daily doses provided by the manufacturers’, even though the majority of patients
Editor,—Thank you for the opportunity to comment on Dr Gibson’s letter. We agree with the suggestions made about the use of NSAID in the perioperative period. At the time we planned our study on a comparison of the analgesic properties of ketoprofen, diclofenac and ketorolac, there was not enough information available on the dose-dependent complications of NSAID, and the maximum doses recommended in Finland were those mentioned in our article. Our primary aim was to compare the analgesic properties of NSAID and to assess if one was superior to the others. During the study, patients were either in the recovery room or in the intensive care unit to allow adequate
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1 James KS, McGrady E, Quasim I, Patrick A. Comparison of extradural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labour. Br J Anaesth 1998; 81: 507–10 2 Beilin Y, Zahn J, Bernstein HH, Zucker-Pinchoff B, Zenzen WJ, Andres LA. Treatment of incomplete analgesia after placement of an epidural catheter and administration of local anesthetic for women in labor. Anesthesiology 1998; 88: 1502–6 3 Morrison LMM, Buchan AS. Comparison of complications with single-holed and multi-holed extradural catheters. Br J Anaesth 1990; 64: 181–3
observation of analgesia and vital functions, including haemodynamic variables and urinary excretion. We have since substantially reduced the dose of NSAID we use in elderly people to those given in the Royal College of Anaesthetists’ guidelines. P. Kostamovaara L. Nuutinen Department of Anaesthesiology Oulu University Hospital Oulu, Finland H. Kokki H. Hendolin Department of Anaesthesiology and Intensive Care Kuopio University Hospital Kuopio, Finland
Epidural analgesia during labour Editor,—While reading the article by James and colleagues,1 comparing 0.25% bupivacaine with 0.1% bupivacaine– 0.0002% fentanyl for epidural analgesia during labour, it would seem that in their enthusiasm for the lower concentration of local anaesthetic mixture, they have overlooked the importance of some of the more negative results of the study. They stated that a total of seven patients were excluded from the study because of failure to maintain analgesic requirements. Five of these were from the mixed bupivacaine and fentanyl group (12.5%); only two were from the plain bupivacaine group (5%). All patients needed bolus doses of 0.5% bupivacaine to obtain satisfactory analgesia, and had deliveries complicated by intervention. Recent emphasis has been placed increasingly on using less local anaesthetic, in combination with an opioid, to produce good or better quality analgesia for the pain of labour. But we must be cautious that we do not ignore the times when the lower doses do not work, and make plans in advance for that inevitable and relatively common event. Almost all articles on the subject show a degree of failure which may be as high as 10–15%,2 3 although this is rarely emphasized. In this study, where the assessment of patient satisfaction was one of the primary goals, it would seem crucial that failures in either technique should be included in the final analysis. Otherwise, we risk advocating analgesic regimens that have an increasing need for the provision of bolus doses of high concentrations of local anaesthetics for increasingly common episodes of breakthrough pain. This would have the potential to re-introduce all the problems and risks that we are striving to avoid. B. M. Miller Manchester Regional Rotation Manchester, UK
Editor,—We read with interest the paper by James and colleagues.1 Ever since the popularization of the mobile epidural by the Queen Charlotte’s group,2 it has been anticipated that the lack of motor block would lead to a lower rate of instrumental deliveries. Up to now this has been hard to demonstrate. Our own study,3 which was very similar in design to that of James and colleagues,1 found no difference, nor did Russell and Reynolds4 or Nageotte and colleagues5 in the USA. Before accepting the conclusion that minimal motor block ‘may influence the progress of labour . . . and incidence of instrumental delivery’ we would raise several points. First, obstetricians are becoming increasingly reluctant to perform mid-cavity or rotational forceps and tend to perform Caesarean section instead. The important outcome is therefore the intervention rate (Caesarean section or forceps) or conversely, the spontaneous vaginal delivery rate (SVD). Second, withdrawing patients from a study such as this may be confounding. In this study, seven women were withdrawn because they requested more than two top-ups within 1 h. In effect, this is selecting out those with particularly painful labours and it is no surprise that six went on to Caesarean section and one to forceps delivery. It would have been better to analyse the data on an intentionto-treat basis, in which case Table 3 would read:
SVD Instrumental Caesarean section
Group A (n J 40)
Group B (n J 40)
27 2 11
22 10 8
In deriving a P value of 0.03 for the instrumental delivery group, the authors appeared to have compared that group with SVD and Caesarean section combined. Even if this is statistically valid it makes no sense clinically. We would suggest that a better way to analyse their data is to compare SVD with interventions (Caesarean section plus instrumental). When analysing all data on an intention-to-treat basis, and hypothesizing that group B will have a higher intervention rate, Fisher’s exact test (one-tailed) yields P 5 0.1794. The studies quoted3–5 all compared a low dose ‘mobile’ epidural with a standard one in a randomized manner and studied 197, 399 and 761 women, respectively. James and colleagues studied only 80 women. While we would con-
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gratulate them on achieving a significantly shorter second stage and showing that, as in other studies, women prefer the mobility of the low-dose epidural, we do not agree that they have demonstrated the decrease in obstetric interventions that it was always hoped would flow from the mobile technique.
P. N. Robinson Department of Anaesthesia Northwick Park and St Mark’s Hospital Harrow, UK 1 James KS, McGrady E, Quasim I, Patrick A. Comparison of epidural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labour. Br J Anaesth 1998; 81: 507–10 2 Robinson PN, Salmon P, Yentis SM. Maternal satisfaction. Int J Obstet Anaesth 1998; 7: 32–7
W. Aveling D. W. L. Davies J. Cooper Department of Anaesthesia University College London Hospitals London, UK 1 James KF, McGrady E, Quasim I, Patrick A. Comparison of epidural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labour. Br J Anaesth 1998; 81: 507–10 2 Collis RE, Baxendall ML, Srikantharajah ID, Edge G, Kadim MY, Morgan BM. Combined spinal epidural with the ability to walk throughout labour. Lancet 1993; 341: 767–8 3 Collis RE, Davies DWL, Aveling W. Randomised comparison of combined spinal–epidural and standard epidural analgesia in labour. Lancet 1995; 343: 1413–16 4 Russell R, Reynolds F. Epidural infusion of low-dose bupivacaine and opioid in labour. Does reducing motor block increase the spontaneous delivery rate? Anaesthesia 1996; 51: 266–73 5 Nageotte MP, Larson D, Rumney PJ, Sidhu M, Hollenbach K. Epidural analgesia compared with combined spinal–epidural analgesia during labor in nulliparous women. N Engl J Med 1997; 337: 1715–19
Editor,—James and colleagues1 deserve congratulations on performing a difficult study comparing a low-dose epidural regimen with 0.25% plain bupivacaine for pain relief in labour. This study supports the existing evidence that lowdose epidural regimens are the techniques of choice in labouring parturients. The value of this study would have been improved if maternal arterial pressure and fetal cardiotocograph (CTG) data had been included, as with both techniques maternal hypotension and subsequent CTG abnormalities may ensue. The first epidural dose in both groups was 15 ml; however, we would suggest that 15 ml of a low-dose solution is not equipotent to 15 ml of 0.25% plain bupivacaine. In our experience, the risk of maternal hypotension developing after a bolus dose of 15 ml of 0.25% plain bupivacaine is very real. Furthermore, 0.25% bupivacaine 15 ml is not a commonly used starting dose in contemporary practice. Concluding that overall maternal satisfaction with the experience of labour is enhanced when assessing only one dimension of the whole process is misleading and erroneous. Measurement by visual analogue scales when assessing maternal satisfaction is not open to meaningful interpretation.2 J. S. Nickells D. J. A. Vaughan D. N. Lucas
Editor,—Thank you for the authors’ comments on our study and the opportunity to reply to these letters. Dr Miller appeared concerned that we advocate the use of low-dose bupivacaine–fentanyl mixtures at the cost of an increased incidence of breakthrough pain. We would like to state that there was no significant difference in the number of women who did not achieve adequate analgesia in the two groups. Also, the proportion of women who required the 0.5% bupivacaine solution or the number of women who ultimately required Caesarean section was no different to what we see in everyday obstetric anaesthetic practice. Every labour ward should have, as we do, guidelines for the management of inadequate epidural analgesia. Dr Aveling and colleagues expressed concern that we are claiming our technique reduces the instrumental delivery rate. What we were suggesting is that low-dose techniques may affect the instrumental delivery rate, which is an altogether different statement; indeed, we could have also selectively quoted the literature as they have done, to support our conclusions.1 2 We should like to point out that our procedure was quite rigid and women were removed from the study if they requested more than two epidural top-ups within a 1-h period, even if they initially had reported pain-free contractions. When these women were removed from the study they were treated quite differently from the remaining study patients and therefore it makes sense not to include them in the final analyses. Our original aim in this study was to compare the analgesic efficacy of the two epidural solutions and not the rate of obstetric interventions. We chose to study 80 patients because our power calculation predicted that we needed 70 patients to have 90% power of detecting a difference of 10 mm in VAS scores for pain during labour. The reduction in instrumental delivery rate was an incidental finding which we thought merited mentioning. If we had undertaken a much larger study it would have reduced our ability to assess the women ourselves during labour; by studying 80 women we were able to adhere meticulously to our procedure. Finally, can we assure Nickells and colleagues that maternal arterial pressure and CTG traces were monitored throughout labour and there was no difference in the incidence of maternal hypotension or CTG abnormalities,
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despite using a 15-ml initial bolus dose. It was necessary to use 15 ml in both arms of the study to facilitate blinding of the operator. We believe that 15 ml of 0.25% bupivacaine is not an excessive dose and that up to 30% of women require this quantity to establish good analgesia. We would also argue that the results of our study demonstrated that 15 ml of a low-dose solution is equipotent to 0.25% bupivacaine 15 ml as all women in the study reported painfree contractions by 30 min. The primary aim of our study was not to compare maternal satisfaction between the two groups; this was a secondary issue and although there are undoubtedly limitations when interpreting VAS, it is still a commonly used technique. If the end-point had been maternal satisfaction, then more detailed analysis would have been appropriate. Again, we would like to state that our reasons for setting up this study were to demonstrate if it was possible to both establish and maintain adequate epidural analgesia using low concentrations of bupivacaine and fentanyl. E. McGrady I. Quasim K. S. James Department of Anaesthetics Glasgow Royal Maternity Hospital Glasgow, Scotland 1 Vertommen JD, et al. The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia during labour and on the incidence of instrumental deliveries. Anesthesiology 1991; 74: 809–14 2 Olofsson C, et al. Obstetric outcome following epidural analgesia with bupivacaine–adrenaline 0.25% or bupivacaine 0.125% with sufentanil—a prospective randomised controlled study in 1000 parturients. Acta Anaesthesiol Scand 1998; 42: 284–92
20 deaths, five re-amputations (excluded from further study) and four patients were not contactable. Furthermore, the effect of preoperative epidural analgesia on stump sensation was studied on a mean number of 19 patients for each modality (range 15–28 patients) with correspondingly small numbers in both the block and control groups. Patient characteristics before operation may also have affected the outcome in both studies. A larger number of patients in the block than in the control group had previous contralateral amputations (seven vs three), a greater median pain score on visual analogue scale (51 mm vs 44 mm) and greater median opioid consumption on admission (50 vs 30 mg morphine/day). This raises the possibility that the block group had greater preoperative central neural sensitization than the control group, which could influence the degree of postoperative pain. Previous studies have suggested a reduction in postoperative phantom limb pain from pre-emptive epidural analgesia.4–7 Although these studies can be criticized for their design and small patient numbers, the study by Nikolajsen, Ilkjaer and Jensen did not provide conclusive evidence against the use of preoperative epidural block in the prevention of phantom limb pain. V. A. Skelton Department of Anaesthesia King’s College Hospital London, UK 1 Nikolajsen L, Ilkjaer S, Jensen TS. Effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees. Br J Anaesth 1998; 81: 348–54 2 Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS. Pain after amputation. Br J Anaesth 1998; 81: 486 3 Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet 1997; 350: 1353–7 4 Katz J. Prevention of phantom-limb pain by regional anaesthesia. Lancet 1997; 349: 519–20 5 Jahangiri M, Bradley JWP, Jayatunga AP, Dark CH. Prevention of phantom limb pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. Ann R Coll Surg Engl 1994; 76: 324–6 6 Bach S, Noreng MF, Tjellden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988; 33: 297–301 7 Schug SA, Burrell R, Payne J, Tester P. Pre-emptive epidural analgesia may prevent phantom limb pain. Reg Anaesth 1995; 20: 256
Epidural bupivacaine and morphine on stump sensation in lower limb amputees Editor,—I was surprised to read the strongly negative conclusion of the recent article on the effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees.1 The same group, in the same issue, corresponded that ‘extradural block . . . does not prevent phantom or stump pain.2 While I accept that the original study on which the article and correspondence were based3 was the most carefully controlled study to date on pre-emptive analgesia in phantom limb pain, the power of the original study was eroded by the high number of patients lost to follow-up; this was not taken into account in the original calculations of the number of patients who needed to be investigated. In the study of the effects of bupivacaine on phantom limb pain, 29 of the original 56 patients (52%) were not followed up; there were
Editor,—Dr Skelton’s main concern seems to be the statistical power of our studies.1 2 Sixty patients were included in the study which examined the effect of preoperative epidural block on phantom pain.1 This number was based on an estimate that a sample size of 27 patients per group would be required (type 1 error rate 0.05; type 2 error rate 0.2; power 5 0.8). After 1 week, 54 patients
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were followed-up: 14 (52%) patients in the epidural block group and 15 (56%) patients in the control group had phantom pain. Mainly because of deaths, a smaller number of patients were followed-up in the later interviews (37, 36 and 28 patients after 3, 6 and 12 months, respectively). At all later interviews, the incidence of phantom pain was slightly higher, although not significantly, in the block group compared with the control group. Dr Skelton quotes four studies which have suggested a reduction in phantom pain from preoperative epidural analgesia.3–6 Katz3 presented no original new data in his commentary but only a short review of previous studies on the subject. In a letter to the editor, Schug and colleagues4 presented data based on 23 patients. The incidence of phantom pain was lower among eight patients who received epidural analgesia before, during and after operation compared with eight patients who received systemic analgesia. Jahangiri and colleagues5 followed prospectively 24 patients who received epidural analgesia before, during and after amputation (n 5 14) or conventional analgesia (n 5 11). The incidence of phantom pain was reduced in the epidural treatment group. Bach, Noreng, Tje´llden6 carried out the only randomized study of 25 patients. None of 11 patients who had received epidural bupivacaine and morphine for 3 days before amputation had phantom pain after 6 months, whereas five patients in the control group had pain. Calculation of statistical power was not presented in any of these studies. We realize that the number of patients was small in our study on the effect of preoperative epidural analgesia on stump sensation.2 Previous studies which claimed an effect of pre-emptive treatment on hyperalgesia and allodynia after surgery examined 20–27 patients.7–9 We cannot exclude the fact that patient characteristics before operation may have influenced the outcome in both studies. However, patients in the block group were treated to freedom from pain during the epidural treatment period, and after amputation the consumption of opioids was similar in both groups. Our studies1 2 do not present conclusive evidence against the use of preoperative epidural block in the prevention of post-amputation pain, hyperalgesia and allodynia. We cannot exclude the possibility that preoperative epidural block for a longer period (1–2 weeks) would prevent these phenomena from developing, but this is not realistic. L. Nikolajsen T. S. Jensen S. Ilkjær University Hospital of Aarhus Aarhus, Denmark 1 Nikolajsen L, Ilkjær S, Christensen JH, Krøner K, Jensen TS. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet 1997; 350: 1353–7 2 Nikolajsen L, Ilkjaer S, Jensen TS. Effect of preoperative extradural
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bupivacaine and morphine on stump sensation in lower limb amputees. Br J Anaesth 1998; 81: 348–54 Katz J. Prevention of phantom-limb pain by regional anaesthesia. Lancet 1997; 349: 519–20 Schug SA, Burrell R, Payne J, Tester P. Pre-emptive epidural analgesia may prevent phantom limb pain. Reg Anaesth 1995; 20: 256 Jahangiri M, Jayatunga AP, Bradley JWP, Dark CH. Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. Ann R Coll Surg Engl 1994; 76: 324–6 Bach S, Noreng MF, Tje´llden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988; 33: 297–301 Stubhaug A, Breivik H, Eide PK, Kreunen M, Foss A. Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization following surgery. Acta Anaesthesiol Scand 1997; 41: 1124–32 Richmond CE, Bromley LM, Woolf CJ. Preoperative morphine pre-empts postoperative pain. Lancet 1993; 342: 73–5 Tverskoy M, Oz Y, Isakson A, Finger J, Bradley EL jr, Kissin I. Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg 1994; 78: 205–9
Postoperative cognitive deficit in the elderly surgical patient Editor,—We read with interest the review article on postoperative cognitive deficit in the elderly surgical patient.1 We agree with the authors that cognitive dysfunction after surgery and anaesthesia is common and persistent, and should be considered seriously. Among other risk factors, cardiopulmonary bypass (CPB) has been blamed for these neurological and neuropsychological deficits. The incidence of neurological abnormalities is quoted to be as high as 61% in the early postoperative period and 17% at the time of discharge from hospital. The incidence of neuropsychological deficits is even higher: 79% in the postoperative period and 38% at the time of discharge.1 The incidence of frank stroke is reported to be as high as 4.8–5.2% overall and in patients who are more than 75 yr of age it approaches 9%.2 In recent years, nuclear medicine has made tremendous advances in studying physiological changes in the brain. Positron emission tomography (PET) and single photon emission computerized tomography (SPECT) provide information on cerebral metabolism and regional cerebral blood flow, respectively. These techniques have been used successfully in studying pathophysiology in patients with neurological and psychiatric illnesses such as Alzheimer’s disease, dementia, Parkinson’s disease and stroke.3 They are also being used in oncology for diagnosis, determining prognosis and guiding treatment. More recently, PET and SPECT scanning have been found to be useful in studying the effects of CPB on cerebral function in patients undergoing cardiac surgery.4 It would be interesting to see if it
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is possible to demonstrate any changes in cerebral metabolism and regional cerebral blood flow in CPB patients and to see how these variables are related to neuropsychological function. R. H. Rehman Department of Anaesthesia P. Kemp Department of Nuclear Medicine Southampton General Hospital Southampton, UK 1 Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth 1998; 81: 449–62 2 Breuer AC, Furlan AJ, Hanson MR, et al. Central nervous system complications of coronary bypass graft surgery: prospective analysis of 421 patients. Stroke 1983; 14: 682–7 3 Ell PJ, Costa DC The role of nuclear medicine in neurology and psychiatry. Curr Opin Neurol Neurosurg 1992; 5: 863–9 4 Marochnick S, Alexandrov AV, Anthone D, Lewin C, Caldwell CB, Pullicino PM. Feasibility of SPECT for studies of brain perfusion during cardiopulmonary bypass. J Neuroimaging 1996; 6: 243–5
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Correspondence Malignant hyperpyrexic syndrome Editor,—The letter to the Lancet by Denborough and Lovell in 1960 and the report of Denborough and colleagues in 1962 are, as pointed out in the commentary by Ellis,1 landmarks for the recognition of malignant hyperthermia (MH) in medical anaesthesia. However, it may be of interest that the syndrome in pigs was, in fact, first described by Hall and colleagues2 and subsequently investigated by the same group3–5 before Harrison’s publication in 1975. Gainsford Harrison visited Cambridge to discuss these investigations and it became obvious that there was a significant difference between the pigs he used (Landrace breed) and the LandraceX pigs in the UK. For example, in South Africa, the experimental condition could be set up in the pure-bred Landrace pigs after induction of general anaesthesia with thiopental whereas in the LandraceX pigs, thiopental appeared to protect from the induction of the syndrome. This led to difficulties in the detailed study of the syndrome in the UK, but indicated that genetic makeup might be implicated in its manifestation. Unfortunately, lack of funding then prevented further work in the UK. It is greatly to Harrison’s credit that he recognized the potential of dantrolene in the prevention and treatment of MH in both pigs and humans but it is perhaps a sad reflexion of our times that it took more than 5 yr before the place of this drug came to be appreciated in medical anaesthesia. Could this have been related to the cost of the drug and its relatively short shelf-life coupled with the failure of those on UK grant-awarding bodies to recognize the need to investigate the potential of this drug in saving lives? L. W. Hall Cambridge, UK 1 Ellis FR. Commentary. Br J Anaesth 1998; 81: 625 2 Hall LW, Woolf N, Bradley JWP, Jolly DW. Unusual reaction to suxamethonium chloride. BMJ 1966; ii: 1305 3 Woolf N, Hall LW, Thorne C, Down M, Walker RG. Serum creatine–phosphokinase levels in pigs reacting abnormally to halogenated anaesthetics. BMJ 1970; iii: 386–7 4 Hall LW, Trim CM, Woolf N. Further studies of porcine malignant hyperthermia. BMJ 1972; ii: 145–8 5 Bradley WG, Ward M, Murchison D, Hall LW, Woolf N. Clinical, electrophysiological and pathological studies in malignant hyperpyrexia. Proc R Soc Med 1973; 66: 67–8
Editor,—I’m pleased Dr Leslie Hall has put on record his own important contributions to our knowledge of malignant
hyperthermia (MH), especially in pigs. His description of succinylcholine-induced MH in 1966 was of course a landmark in this field, although difficult to interpret in the light of later findings. He points out the discrepancies in the pig research and this indeed highlights that there are important discrepancies between the pig syndrome and MH in humans. F. R. Ellis University of Leeds St James’s University Hospital Leeds, UK
Early clinical experience with a newly formulated hydroxyethyl starch—Hextend Editor,—We would like to report our early experience with a newly formulated hydroxyethyl starch (HES), Hextend (BioTime Inc, Berkeley, CA, USA). Currently, clinicians are re-evaluating their blood transfusion policies with both economic and safety issues driving the reduction in use of donated human blood products. Increasing surgical demands have increased the volumes of artificial colloids to which patients are exposed. New concerns about the uses of human albumin solution1 intensify the search for a ‘colloid of choice’. Hextend is a medium molecular weight HES (450 kDa) formulated with mixed electrolytes (sodium 141 mmol litre–1, chloride 124 mmol litre–1, potassium 3.0 mmol litre–1, calcium 2.55 mmol litre–1, magnesium 0.9 mmol litre–1), lactate and glucose to preserve a more ‘plasma-like’ physiological milieu than in other comparable artificial colloids. In previously presented HES solutions, the suspending medium was 0.9% saline solution with chloride 154 mmol litre–1. It is becoming apparent that our ability to tolerate a high chloride load is imperfect and that, particularly in the presence of renal compromise, such a load can lead to the development of acid–base disturbance.2 In an open label study, Hextend was administered for the first time to humans to evaluate its efficacy and safety. Five patients have so far received Hextend 500–3150 ml, administered according to a treatment algorithm. It proved to be an effective volume expander achieving the algorithm goals which triggered infusion. Changes in measured electrolytes outside normal limits were not seen in any patient. We performed detailed in vitro coagulation studies and observed predictable changes in factor VIII moieties from previous experience with HES of molecular weight 450 kDa. There were no idiosyncratic effects observed.
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The HES component of Hextend represents a return to higher molecular weight moieties. Lower molecular weight HES have been reported to have less effect on the coagulation system, particularly factor VIII associated proteins, although the clinical significance of this in terms of bleeding is vague.3 The prolonged intravascular persistence of a higher molecular weight HES may offer advantages in isovolaemic haemodilution which outweigh its poorly defined effect on blood coagulation in this type of application. We suggest that this agent may be a useful adjuvant to volume therapy and that further evaluation may identify the importance of physiological balance in large volume transfusion of artificial colloid. R. L. Woolf M. V. Chapman M. G. Mythen Department of Anaesthesia University College London Hospitals London, UK
additional opioids in the doses mentioned. Any differences between study groups may be too small to detect in a small number of patients. We agree with the authors1 that a clinically useful application of pre-emptive analgesia with morphine may not be possible because of the need for the return of spontaneous respiration at the end of surgery. Whether use of drugs such as remifentanil, which would allow a greater dose and antinociceptive effect during operation, will demonstrate pre-emptive analgesia remains to be seen. N. A. Randhawa P. P. Bapat Department of Anaesthetics West Middlesex University Hospital Isleworth, Middlesex, UK 1 Millar AY, Mansfield MD, Kinsella J. Influence of timing of morphine administration on postoperative pain and analgesic consumption. Br J Anaesth 1998; 81: 373–6 2 Finck AD, Samaniego E, Nagai SH. Nitrous oxide selectively releases Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 into canine third ventricular cerebrospinal fluid. Anesth Analg 1995; 80: 664–70 3 Yang JC, Clark WC, Ngai SH. Antagonism of nitrous oxide analgesia by naloxone in man. Anesthesiology 1980; 52: 424–7 4 Goto T, Marota JJ, Crosby G. Nitrous oxide induces preemptive analgesia in the rat that is antagonized by halothane. Anesthesiology 1994; 80: 409–16 5 O’Connor TC, Abram SE. Inhibition of nociception induced spinal sensitisation by anesthetic agents. Anesthesiology 1995; 82: 259–66
1 Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ 1998; 317: 235–40 2 Mathes DD, Morell RC, Rohr MS. Dilutional acidosis: is it a real clinical entity? Anesthesiology 1997; 86: 501–3 3 Treib J, Haass A, Pindur G. Influence on intravascular molecular weight of hydroxyethyl starch on platelets during a long term haemodilution. Thromb Haemost 1997; 78: 974–83
Pre-emptive analgesia—why the evidence is Editor,—We accept the possibility that the use of nitrous oxide may act as a confounding variable when looking conflicting for a pre-emptive analgesic effect using another analgesic. Editor,—We read with interest the article by Millar, Mansfield and Kinsella1 and would like to raise some points for discussion. They have given several reasons for failure to demonstrate pre-emptive analgesia in various studies. Another potential reason may be the inclusion of nitrous oxide in the design of all clinical studies. The analgesic effect of nitrous oxide is probably a result of involvement of the proenkephalin derived family of endogenous opioids.2 This finding is further supported by the fact that naloxone antagonizes the analgesic effect of nitrous oxide.3 Nitrous oxide has been shown to produce pre-emptive analgesia in rats.4 Interestingly, in the same study, it was reported that halothane antagonized the analgesic effect of nitrous oxide. However, another animal study5 showed inhibition of nociception-induced spinal sensitization by most anaesthetic agents, except halothane. Whether a similar effect occurs in humans is not known. It is not inconceivable that the use of 66% nitrous oxide has a pre-emptive effect which is not greatly improved by
However, we do not think this is a valid concern for the following reasons. First, in humans, nitrous oxide is a very weak analgesic and it is difficult to believe that it alone could prevent noxious stimuli from having an effect on the spinal cord. Second, if nitrous oxide were to have a pre-emptive influence, we might expect that those subjects anaesthetized with nitrous oxide would have reduced analgesic requirements after operation compared with those anaesthetized breathing air–oxygen mixtures. This was not noted in our clinical experience and has not been demonstrated when studied in humans.1 2 A.Y. Millar J. Kinsella Directorate of Anaesthesia Glasgow Royal Infirmary Glasgow, UK
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1 Krogh B, Jorn Jensen P, Henneberg SW, Hole P, Kronborg O. Nitrous oxide does not influence operating conditions or
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postoperative course in colonic surgery. Br J Anaesth 1994; 72: 55–7 2 Jensen AG, Prevedoros H, Kullman E, Anderberg B, Lennmarken C. Peroperative nitrous oxide does not influence recovery after laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1993; 37: 683–6
Cisatracurium in a patient with atypical plasma cholinesterase Editor,—Cisatracurium is one of the 10 stereoisomers that constitute atracurium. As with atracurium, cisatracurium undergoes spontaneous non-organ-dependent Hofmann degradation at physiological pH and temperature. Unlike atracurium, non-specific ester hydrolysis does not appear to play a significant role in the degradation of cisatracurium1–6: 80% of a dose of cisatracurium is cleared by non-organdependent Hofmann elimination. With both drugs, the liver and kidneys play only a minor role in elimination.1–5 The non-specific ester hydrolysis of atracurium is independent of plasma cholinesterase activity. In vitro experiments have shown that the rates of breakdown of atracurium are not different when the drug is incubated in normal plasma or in plasma obtained from genetically deficient homozygous patients with virtually no plasma cholinesterase activity.7 This finding has been confirmed clinically; we have shown, using electromyography, a normal response to atracurium in a homozygous patient with atypical cholinesterase activity.8 The following case report investigates the neuromuscular blocking effect of cisatracurium in a patient with atypical plasma cholinesterase activity. A 57-yr-old male, weighing 100 kg, was scheduled for nasoplasty. During previous surgery, he received succinylcholine 75 mg for tracheal intubation, which was followed by prolonged neuromuscular block lasting 7 h. Because of this history, plasma cholinesterase concentrations and dibucaine number were estimated before the present operation. Plasma cholinesterase activity was 2.3 units (normal value 2.5–4.5 units) and dibucaine number was 35, suggesting homozygote atypical plasma cholinesterase activity. The patient was premedicated with glycopyrrolate 0.2 mg i.m. and diazepam 5 mg orally. Anaesthesia was induced with propofol 2 mg kg–1, lidocaine 1 mg kg–1 and fentanyl 1.5 µg kg–1. Neuromuscular transmission was monitored using a Datex electromyograph. The ulnar nerve was stimulated supramaximally at the wrist every 20 s using the trainof-four (TOF) twitch technique at a stimulus rate of 2 Hz. A bolus dose of cisatracurium 0.15 mg kg–1 (3 3 ED95) was then given. Complete neuromuscular block was achieved after 120 s, when tracheal intubation was performed easily. Anaesthesia was maintained with 1% isoflurane and 66% nitrous oxide in oxygen. After 20 min, 25% recovery of the first twitch of the TOF was observed, and a maintenance dose of cisatracurium
0.05 mg kg–1 was given. At the end of surgery, which lasted 60 min, 50% recovery of the first twitch of the TOF was observed. Residual neuromuscular block was antagonized successfully using neostigmine 0.05 mg kg– 1 and glycopyrrolate 0.01 mg kg–1. The twitch response was restored completely, and tetanus was maintained with no post-tetanic facilitation. This report confirms that cisatracurium, in common with atracurium,8 can be used safely in patients with atypical plasma cholinesterase. A. Baraka A. Soueidi C. Berzina Department of Anesthesiology American University of Beirut Beirut, Lebanon 1 Lien CA, Schmith VD, Belmont MR, Kisor D, Savarese JJ. Pharmacokinetics/dynamics of 51W89 in patients during opioid anesthesia. Anesthesiology 1994; 81: A1090 2 Ornstein E, Lien CA, Matteo RS, et al. Pharmacodynamics and pharmacokinetics of 51W89 in geriatric surgical patients. Anesthesiology 1994; 81: A1075 3 Dewolf AM, Freeman F, Scott V, et al. Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end stage liver disease undergoing liver transplantation. Anesthesiology 1994; 81: A1075 4 Eastwood NB, Boyd AH, Parker MA, Hunter JM. Pharmacokinetics of 1R-cis 19R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure. Br J Anaesth 1995; 74: 400–4 5 Boyd AH, Eastwood NB, Parker CJR, Hunter JM. A comparison of the pharmacodynamics and pharmacokinetics of an infusion of cisatracurium (51W89) or atracurium in critically ill patients undergoing mechanical ventilation in the intensive therapy unit. Br J Anaesth 1996; 76: 382–8 6 Kisor D, Wargin WA, Schmith VD, Cook DR, Ornstein E. Organ independent elimination of 51W89. Pharmacol Res 1994; 11: S335 7 Merrett RA, Thompson CW, Webb FW. In vitro degradation of atracurium in human plasma. Br J Anaesth 1983; 55: 61–6 8 Baraka A, Abu Jaoude C. Atracurium in a parturient with atypical cholinesterase. Br J Anaesth 1984; 56: 930–1
Epidural anaesthesia for Caesarean section in an achondroplastic dwarf Editor,—We were interested to read the case report by Morrow and Black1 describing the anaesthetic management of an achondroplastic dwarf undergoing Caesarean section. As the authors stated, such patients present a significant challenge for the anaesthetist, and yet there is little information in the literature to guide effective management. Most of the published work consists of case reports and, in common with the present account, relate to anaesthesia for elective Caesarean section where time is available to
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perform central neural block using an epidural or microspinal catheter. Having recently found ourselves in a similar situation,2 we would be interested in how the authors might have managed their case for an emergency Caesarean section, when time constraints may preclude the use of an incremental technique, and yet the patient is keen to be awake for delivery. A. Ravenscroft C. Rout Department of Anaesthesia University of Natal Durban, South Africa 1 Morrow MJ, Black IH. Epidural anaesthesia for Caesarean section in an achondroplastic dwarf. Br J Anaesth 1998; 81: 619–21 2 Ravenscroft AJ, Govendor T, Rout C. Spinal anaesthesia for emergency caesarean section in an achondroplastic dwarf. Anaesthesia 1998; 53: 1236–7
Editor,—We appreciate the interest in our article1 shown by Drs Ravenscroft and Rout and are grateful for the opportunity to reply. There are few guidelines on the use of epidural or spinal anaesthesia in the gravid achondroplastic dwarf; most of the available data are derived from a small number of case reports. In one such letter, Crawford and Dutton2 reported that infusion of 0.5% hyperbaric bupivacaine 0.5 ml intrathecally resulted in bilateral block to T6 within 20 min, and that the block was associated with significant hypotension. The intra-abdominal position of the uterus in patients with achondroplasia may result in particularly severe aorto-caval compression.3–5 When this problem is compounded by the sudden onset of central neural block, there is the possibility that catastrophic hypotension may result. In a series of patients of normal stature undergoing elective Caesarean section, Robson and colleagues demonstrated that a marked decrease in cardiac output occurs after spinal anaesthesia,6 but that such a decrease is not associated with epidural anaesthesia or an incremental spinal technique.7 It is debatable whether this work is applicable to patients with achondroplasia. However, in the absence of data indicating otherwise, it would seem reasonable to assume that a similar, if not greater, reduction in cardiac output may result when rapid onset of spinal block occurs in this subgroup of patients. We considered initially the use of a ‘single-shot’ spinal technique but decided against this approach when it became apparent that the combination of factors outlined above made it potentially hazardous, particularly if general anaesthesia was required in the event of a failed spinal block. Before siting the epidural, we decided that in the event of accidental dural puncture, the operator would pass the epidural catheter into the subarachnoid space and we would perform the procedure under incremental spinal anaesthesia. Faced with a similar situation to that described
by Drs Ravenscroft and Rout, our choice would be to perform an elective dural puncture using an 18-gauge Tuohy needle, pass the catheter intrathecally and establish spinal block using a small dose of 0.5% hyperbaric bupivacaine. An initial dose of 0.3 ml, followed by 0.1 ml increments as required to achieve surgical block would be our approach. Invasive arterial pressure monitoring would be advisable. We feel that the use of intrathecal opioids should be treated with extreme caution in this situation, in view of the potential for unpredictable spread of the injectate within the cerebrospinal fluid in achondroplastic patients. The relatively small time delay involved in the use of this approach would, in our opinion, outweigh the potential risks of severe hypotension and unpredictable block height (with the consequent need for general anaesthesia) that could result from the use of a ‘single-shot’ spinal injection. We believe that the use of an incremental technique should not necessarily be ruled out in the emergency situation. The amount of time spent establishing an incremental surgical block should account for a relatively small proportion of the overall anaesthetic time spent in patient preparation and accessing the subarachnoid space, and would add to the overall safety of the procedure. Obviously, the use of such an approach would result in a higher risk of post-dural puncture headache and the use of standard guidelines aimed at minimizing its occurrence should be adopted. Should the need arise, epidural blood patching may be attempted at a later date under less stressful conditions. Adequate preparation time for any form of central neural block is fundamental to the successful outcome of the procedure, and the role of good communication between all members of the team involved in the perinatal care of this group of patients is of the utmost importance. M. J. Morrow Royal Maternity Hospital Grosvenor Road Belfast, Northern Ireland I. H. Black Antrim Area Hospital Antrim, Northern Ireland
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1 Morrow MJ, Black IH. Epidural anaesthesia for Caesarean section in an achondroplastic dwarf. Br J Anaesth 1998; 81: 619–21 2 Crawford M, Dutton DA. Spinal anaesthesia for caesarean section in an achondroplastic dwarf. Anaesthesia 1992; 47: 1007 3 Brimacombe JR, Caunt JA. Anaesthesia in a gravid achondroplastic dwarf. Anesthesia 1990; 45: 132–4 4 Cohen SE. Anaesthesia for Cesarean section in achondroplastic dwarfs. Anesthesiology 1980; 52: 264–6 5 Wardall GJ, Frame WT. Extradural anaesthesia for Caesarean section in achondroplasia. Br J Anaesth 1990; 64: 367–70 6 Robson SC, Boys RJ, Rodeck C, Morgan B. Maternal and fetal haemodynamic effects of spinal and extradural anaesthesia for elective Caesarean section. Br J Anaesth 1992; 68: 54–9
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7 Robson SC, Samsoon G, Boys RJ, Rodeck C, Morgan B. Incremental spinal anaesthesia for elective Caesarean section: maternal and fetal haemodynamic effects. Br J Anaesth 1993; 70: 634–8
Inadvertent inhalation anaesthesia during surgery under retrobulbar eye block Editor,—I read with concern Dr Smith’s case report on inadvertent inhalation anaesthesia during surgery under retrobulbar eye block.1 It is axiomatic that equipment should not be used without first being checked. It is clear that the anaesthetic machine used in the case described had not been checked before use. It is just as clear that this arose from its being used by someone other than an anaesthetist. This must be identified as the sole cause of the near fatal accident. We do not allow anyone to drive or fly without a licence. We should not allow anyone to use an anaesthetic machine except an anaesthetist. A wall mounted oxygen flow meter, such as is used routinely in recovery and ICU, should be the sole method by which non-anaesthetists are allowed to administer oxygen in theatre. I would not even allow its mounting on the anaesthetic machine, as shown in Dr Smith’s photograph. There should be no exceptions. C. P. H. Heneghan Nevill Hall Hospital Abergavenny, UK
recruited were elderly (age range 54–81 yr) and some had severe disease (ASA III), warrants comment. The authors stated that ‘short-term NSAIDs for surgical patients does not seem to induce irreversible renal failure’. However, NSAIDs are implicated in up to 15.6% of druginduced reports of acute renal failure (ARF),2 and although most patients recover with appropriate management, the relatively rare complications of papillary necrosis and interstitial nephritis can be irreversible. NSAID-induced ARF is often pre-renal. Known risk factors include old age, volume depletion from diuretics and other causes such as postoperative bleeding, congestive heart failure, diabetes mellitus and renal impairment; risk is also dose-dependent.3 For these reasons, the manufacturers of all three drugs recommend a reduction in dose when these drugs are used in the elderly. For instance, the maximum recommended dose of ketorolac is 60 mg in 24 h, which is half the dose used in this study. Indeed, the incidence of serious and fatal adverse events reported with ketorolac has decreased since revision of dosage guidelines.4 Finally, recent guidelines on the use of NSAIDs in the perioperative period advise that they should be used with caution in these conditions and that renal function should be monitored regularly in patients after major surgery.5 F. A. M. Gibson Department of Anaesthesia St Thomas’s Hospital London, UK 1 Kostamovaara PA, Hendolin H, Kokki H, Nuutinen LS. Ketorolac, diclofenac and ketoprofen are equally efficacious for pain relief after total hip replacement. Br J Anaesth 1998; 81: 369–72 2 Delmas PD. Non-steroidal anti-inflammatory drugs and renal function. Br J Rheumatol 1995; 34 (Suppl. 1): 25–8 3 Perez Gutthann S, Garcia Rodriguez LA, Raiford DS, Duque OA, Ris Romeu J. Non-steroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure. Arch Intern Med 1996; 156: 2433–9 4 Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 1997; 53: 139–88 5 Guidelines for the Use of Non-Steroidal Anti-inflammatory Drugs in the Peri-operative Period. London: Royal College of Anaesthetists, 1998
1 Smith WQ. Inadvertent inhalation anaesthesia during surgery under retrobulbar eye block. Br J Anaesth 1998; 81: 793–4
Editor,—Thank you for the opportunity to respond to Dr Heneghan’s letter. He has succinctly summarized a corollary of the conclusions in my case report: that if surgery is undertaken in the absence of an anaesthetist, then it is the operating surgeon who bears the full responsibility for the total care of that patient. While this apportions responsibility, undoubtedly it would be more appropriate for an anaesthetist to be in attendance in such circumstances. Q. Smith City Hospitals Sunderland Sunderland Royal Hospital Sunderland, UK
Reduce dose of NSAIDs in the elderly Editor,—I read with interest the article by Kostamovaara and colleagues comparing ketorolac, diclofenac and ketoprofen for pain relief after total hip surgery.1 The authors’ use of the ‘recommended maximal daily doses provided by the manufacturers’, even though the majority of patients
Editor,—Thank you for the opportunity to comment on Dr Gibson’s letter. We agree with the suggestions made about the use of NSAID in the perioperative period. At the time we planned our study on a comparison of the analgesic properties of ketoprofen, diclofenac and ketorolac, there was not enough information available on the dose-dependent complications of NSAID, and the maximum doses recommended in Finland were those mentioned in our article. Our primary aim was to compare the analgesic properties of NSAID and to assess if one was superior to the others. During the study, patients were either in the recovery room or in the intensive care unit to allow adequate
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1 James KS, McGrady E, Quasim I, Patrick A. Comparison of extradural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labour. Br J Anaesth 1998; 81: 507–10 2 Beilin Y, Zahn J, Bernstein HH, Zucker-Pinchoff B, Zenzen WJ, Andres LA. Treatment of incomplete analgesia after placement of an epidural catheter and administration of local anesthetic for women in labor. Anesthesiology 1998; 88: 1502–6 3 Morrison LMM, Buchan AS. Comparison of complications with single-holed and multi-holed extradural catheters. Br J Anaesth 1990; 64: 181–3
observation of analgesia and vital functions, including haemodynamic variables and urinary excretion. We have since substantially reduced the dose of NSAID we use in elderly people to those given in the Royal College of Anaesthetists’ guidelines. P. Kostamovaara L. Nuutinen Department of Anaesthesiology Oulu University Hospital Oulu, Finland H. Kokki H. Hendolin Department of Anaesthesiology and Intensive Care Kuopio University Hospital Kuopio, Finland
Epidural analgesia during labour Editor,—While reading the article by James and colleagues,1 comparing 0.25% bupivacaine with 0.1% bupivacaine– 0.0002% fentanyl for epidural analgesia during labour, it would seem that in their enthusiasm for the lower concentration of local anaesthetic mixture, they have overlooked the importance of some of the more negative results of the study. They stated that a total of seven patients were excluded from the study because of failure to maintain analgesic requirements. Five of these were from the mixed bupivacaine and fentanyl group (12.5%); only two were from the plain bupivacaine group (5%). All patients needed bolus doses of 0.5% bupivacaine to obtain satisfactory analgesia, and had deliveries complicated by intervention. Recent emphasis has been placed increasingly on using less local anaesthetic, in combination with an opioid, to produce good or better quality analgesia for the pain of labour. But we must be cautious that we do not ignore the times when the lower doses do not work, and make plans in advance for that inevitable and relatively common event. Almost all articles on the subject show a degree of failure which may be as high as 10–15%,2 3 although this is rarely emphasized. In this study, where the assessment of patient satisfaction was one of the primary goals, it would seem crucial that failures in either technique should be included in the final analysis. Otherwise, we risk advocating analgesic regimens that have an increasing need for the provision of bolus doses of high concentrations of local anaesthetics for increasingly common episodes of breakthrough pain. This would have the potential to re-introduce all the problems and risks that we are striving to avoid. B. M. Miller Manchester Regional Rotation Manchester, UK
Editor,—We read with interest the paper by James and colleagues.1 Ever since the popularization of the mobile epidural by the Queen Charlotte’s group,2 it has been anticipated that the lack of motor block would lead to a lower rate of instrumental deliveries. Up to now this has been hard to demonstrate. Our own study,3 which was very similar in design to that of James and colleagues,1 found no difference, nor did Russell and Reynolds4 or Nageotte and colleagues5 in the USA. Before accepting the conclusion that minimal motor block ‘may influence the progress of labour . . . and incidence of instrumental delivery’ we would raise several points. First, obstetricians are becoming increasingly reluctant to perform mid-cavity or rotational forceps and tend to perform Caesarean section instead. The important outcome is therefore the intervention rate (Caesarean section or forceps) or conversely, the spontaneous vaginal delivery rate (SVD). Second, withdrawing patients from a study such as this may be confounding. In this study, seven women were withdrawn because they requested more than two top-ups within 1 h. In effect, this is selecting out those with particularly painful labours and it is no surprise that six went on to Caesarean section and one to forceps delivery. It would have been better to analyse the data on an intentionto-treat basis, in which case Table 3 would read:
SVD Instrumental Caesarean section
Group A (n J 40)
Group B (n J 40)
27 2 11
22 10 8
In deriving a P value of 0.03 for the instrumental delivery group, the authors appeared to have compared that group with SVD and Caesarean section combined. Even if this is statistically valid it makes no sense clinically. We would suggest that a better way to analyse their data is to compare SVD with interventions (Caesarean section plus instrumental). When analysing all data on an intention-to-treat basis, and hypothesizing that group B will have a higher intervention rate, Fisher’s exact test (one-tailed) yields P 5 0.1794. The studies quoted3–5 all compared a low dose ‘mobile’ epidural with a standard one in a randomized manner and studied 197, 399 and 761 women, respectively. James and colleagues studied only 80 women. While we would con-
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gratulate them on achieving a significantly shorter second stage and showing that, as in other studies, women prefer the mobility of the low-dose epidural, we do not agree that they have demonstrated the decrease in obstetric interventions that it was always hoped would flow from the mobile technique.
P. N. Robinson Department of Anaesthesia Northwick Park and St Mark’s Hospital Harrow, UK 1 James KS, McGrady E, Quasim I, Patrick A. Comparison of epidural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labour. Br J Anaesth 1998; 81: 507–10 2 Robinson PN, Salmon P, Yentis SM. Maternal satisfaction. Int J Obstet Anaesth 1998; 7: 32–7
W. Aveling D. W. L. Davies J. Cooper Department of Anaesthesia University College London Hospitals London, UK 1 James KF, McGrady E, Quasim I, Patrick A. Comparison of epidural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with 0.0002% fentanyl for analgesia during labour. Br J Anaesth 1998; 81: 507–10 2 Collis RE, Baxendall ML, Srikantharajah ID, Edge G, Kadim MY, Morgan BM. Combined spinal epidural with the ability to walk throughout labour. Lancet 1993; 341: 767–8 3 Collis RE, Davies DWL, Aveling W. Randomised comparison of combined spinal–epidural and standard epidural analgesia in labour. Lancet 1995; 343: 1413–16 4 Russell R, Reynolds F. Epidural infusion of low-dose bupivacaine and opioid in labour. Does reducing motor block increase the spontaneous delivery rate? Anaesthesia 1996; 51: 266–73 5 Nageotte MP, Larson D, Rumney PJ, Sidhu M, Hollenbach K. Epidural analgesia compared with combined spinal–epidural analgesia during labor in nulliparous women. N Engl J Med 1997; 337: 1715–19
Editor,—James and colleagues1 deserve congratulations on performing a difficult study comparing a low-dose epidural regimen with 0.25% plain bupivacaine for pain relief in labour. This study supports the existing evidence that lowdose epidural regimens are the techniques of choice in labouring parturients. The value of this study would have been improved if maternal arterial pressure and fetal cardiotocograph (CTG) data had been included, as with both techniques maternal hypotension and subsequent CTG abnormalities may ensue. The first epidural dose in both groups was 15 ml; however, we would suggest that 15 ml of a low-dose solution is not equipotent to 15 ml of 0.25% plain bupivacaine. In our experience, the risk of maternal hypotension developing after a bolus dose of 15 ml of 0.25% plain bupivacaine is very real. Furthermore, 0.25% bupivacaine 15 ml is not a commonly used starting dose in contemporary practice. Concluding that overall maternal satisfaction with the experience of labour is enhanced when assessing only one dimension of the whole process is misleading and erroneous. Measurement by visual analogue scales when assessing maternal satisfaction is not open to meaningful interpretation.2 J. S. Nickells D. J. A. Vaughan D. N. Lucas
Editor,—Thank you for the authors’ comments on our study and the opportunity to reply to these letters. Dr Miller appeared concerned that we advocate the use of low-dose bupivacaine–fentanyl mixtures at the cost of an increased incidence of breakthrough pain. We would like to state that there was no significant difference in the number of women who did not achieve adequate analgesia in the two groups. Also, the proportion of women who required the 0.5% bupivacaine solution or the number of women who ultimately required Caesarean section was no different to what we see in everyday obstetric anaesthetic practice. Every labour ward should have, as we do, guidelines for the management of inadequate epidural analgesia. Dr Aveling and colleagues expressed concern that we are claiming our technique reduces the instrumental delivery rate. What we were suggesting is that low-dose techniques may affect the instrumental delivery rate, which is an altogether different statement; indeed, we could have also selectively quoted the literature as they have done, to support our conclusions.1 2 We should like to point out that our procedure was quite rigid and women were removed from the study if they requested more than two epidural top-ups within a 1-h period, even if they initially had reported pain-free contractions. When these women were removed from the study they were treated quite differently from the remaining study patients and therefore it makes sense not to include them in the final analyses. Our original aim in this study was to compare the analgesic efficacy of the two epidural solutions and not the rate of obstetric interventions. We chose to study 80 patients because our power calculation predicted that we needed 70 patients to have 90% power of detecting a difference of 10 mm in VAS scores for pain during labour. The reduction in instrumental delivery rate was an incidental finding which we thought merited mentioning. If we had undertaken a much larger study it would have reduced our ability to assess the women ourselves during labour; by studying 80 women we were able to adhere meticulously to our procedure. Finally, can we assure Nickells and colleagues that maternal arterial pressure and CTG traces were monitored throughout labour and there was no difference in the incidence of maternal hypotension or CTG abnormalities,
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despite using a 15-ml initial bolus dose. It was necessary to use 15 ml in both arms of the study to facilitate blinding of the operator. We believe that 15 ml of 0.25% bupivacaine is not an excessive dose and that up to 30% of women require this quantity to establish good analgesia. We would also argue that the results of our study demonstrated that 15 ml of a low-dose solution is equipotent to 0.25% bupivacaine 15 ml as all women in the study reported painfree contractions by 30 min. The primary aim of our study was not to compare maternal satisfaction between the two groups; this was a secondary issue and although there are undoubtedly limitations when interpreting VAS, it is still a commonly used technique. If the end-point had been maternal satisfaction, then more detailed analysis would have been appropriate. Again, we would like to state that our reasons for setting up this study were to demonstrate if it was possible to both establish and maintain adequate epidural analgesia using low concentrations of bupivacaine and fentanyl. E. McGrady I. Quasim K. S. James Department of Anaesthetics Glasgow Royal Maternity Hospital Glasgow, Scotland 1 Vertommen JD, et al. The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia during labour and on the incidence of instrumental deliveries. Anesthesiology 1991; 74: 809–14 2 Olofsson C, et al. Obstetric outcome following epidural analgesia with bupivacaine–adrenaline 0.25% or bupivacaine 0.125% with sufentanil—a prospective randomised controlled study in 1000 parturients. Acta Anaesthesiol Scand 1998; 42: 284–92
20 deaths, five re-amputations (excluded from further study) and four patients were not contactable. Furthermore, the effect of preoperative epidural analgesia on stump sensation was studied on a mean number of 19 patients for each modality (range 15–28 patients) with correspondingly small numbers in both the block and control groups. Patient characteristics before operation may also have affected the outcome in both studies. A larger number of patients in the block than in the control group had previous contralateral amputations (seven vs three), a greater median pain score on visual analogue scale (51 mm vs 44 mm) and greater median opioid consumption on admission (50 vs 30 mg morphine/day). This raises the possibility that the block group had greater preoperative central neural sensitization than the control group, which could influence the degree of postoperative pain. Previous studies have suggested a reduction in postoperative phantom limb pain from pre-emptive epidural analgesia.4–7 Although these studies can be criticized for their design and small patient numbers, the study by Nikolajsen, Ilkjaer and Jensen did not provide conclusive evidence against the use of preoperative epidural block in the prevention of phantom limb pain. V. A. Skelton Department of Anaesthesia King’s College Hospital London, UK 1 Nikolajsen L, Ilkjaer S, Jensen TS. Effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees. Br J Anaesth 1998; 81: 348–54 2 Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS. Pain after amputation. Br J Anaesth 1998; 81: 486 3 Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet 1997; 350: 1353–7 4 Katz J. Prevention of phantom-limb pain by regional anaesthesia. Lancet 1997; 349: 519–20 5 Jahangiri M, Bradley JWP, Jayatunga AP, Dark CH. Prevention of phantom limb pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. Ann R Coll Surg Engl 1994; 76: 324–6 6 Bach S, Noreng MF, Tjellden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988; 33: 297–301 7 Schug SA, Burrell R, Payne J, Tester P. Pre-emptive epidural analgesia may prevent phantom limb pain. Reg Anaesth 1995; 20: 256
Epidural bupivacaine and morphine on stump sensation in lower limb amputees Editor,—I was surprised to read the strongly negative conclusion of the recent article on the effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees.1 The same group, in the same issue, corresponded that ‘extradural block . . . does not prevent phantom or stump pain.2 While I accept that the original study on which the article and correspondence were based3 was the most carefully controlled study to date on pre-emptive analgesia in phantom limb pain, the power of the original study was eroded by the high number of patients lost to follow-up; this was not taken into account in the original calculations of the number of patients who needed to be investigated. In the study of the effects of bupivacaine on phantom limb pain, 29 of the original 56 patients (52%) were not followed up; there were
Editor,—Dr Skelton’s main concern seems to be the statistical power of our studies.1 2 Sixty patients were included in the study which examined the effect of preoperative epidural block on phantom pain.1 This number was based on an estimate that a sample size of 27 patients per group would be required (type 1 error rate 0.05; type 2 error rate 0.2; power 5 0.8). After 1 week, 54 patients
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were followed-up: 14 (52%) patients in the epidural block group and 15 (56%) patients in the control group had phantom pain. Mainly because of deaths, a smaller number of patients were followed-up in the later interviews (37, 36 and 28 patients after 3, 6 and 12 months, respectively). At all later interviews, the incidence of phantom pain was slightly higher, although not significantly, in the block group compared with the control group. Dr Skelton quotes four studies which have suggested a reduction in phantom pain from preoperative epidural analgesia.3–6 Katz3 presented no original new data in his commentary but only a short review of previous studies on the subject. In a letter to the editor, Schug and colleagues4 presented data based on 23 patients. The incidence of phantom pain was lower among eight patients who received epidural analgesia before, during and after operation compared with eight patients who received systemic analgesia. Jahangiri and colleagues5 followed prospectively 24 patients who received epidural analgesia before, during and after amputation (n 5 14) or conventional analgesia (n 5 11). The incidence of phantom pain was reduced in the epidural treatment group. Bach, Noreng, Tje´llden6 carried out the only randomized study of 25 patients. None of 11 patients who had received epidural bupivacaine and morphine for 3 days before amputation had phantom pain after 6 months, whereas five patients in the control group had pain. Calculation of statistical power was not presented in any of these studies. We realize that the number of patients was small in our study on the effect of preoperative epidural analgesia on stump sensation.2 Previous studies which claimed an effect of pre-emptive treatment on hyperalgesia and allodynia after surgery examined 20–27 patients.7–9 We cannot exclude the fact that patient characteristics before operation may have influenced the outcome in both studies. However, patients in the block group were treated to freedom from pain during the epidural treatment period, and after amputation the consumption of opioids was similar in both groups. Our studies1 2 do not present conclusive evidence against the use of preoperative epidural block in the prevention of post-amputation pain, hyperalgesia and allodynia. We cannot exclude the possibility that preoperative epidural block for a longer period (1–2 weeks) would prevent these phenomena from developing, but this is not realistic. L. Nikolajsen T. S. Jensen S. Ilkjær University Hospital of Aarhus Aarhus, Denmark 1 Nikolajsen L, Ilkjær S, Christensen JH, Krøner K, Jensen TS. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet 1997; 350: 1353–7 2 Nikolajsen L, Ilkjaer S, Jensen TS. Effect of preoperative extradural
3 4
5
6
7
8 9
bupivacaine and morphine on stump sensation in lower limb amputees. Br J Anaesth 1998; 81: 348–54 Katz J. Prevention of phantom-limb pain by regional anaesthesia. Lancet 1997; 349: 519–20 Schug SA, Burrell R, Payne J, Tester P. Pre-emptive epidural analgesia may prevent phantom limb pain. Reg Anaesth 1995; 20: 256 Jahangiri M, Jayatunga AP, Bradley JWP, Dark CH. Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. Ann R Coll Surg Engl 1994; 76: 324–6 Bach S, Noreng MF, Tje´llden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988; 33: 297–301 Stubhaug A, Breivik H, Eide PK, Kreunen M, Foss A. Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization following surgery. Acta Anaesthesiol Scand 1997; 41: 1124–32 Richmond CE, Bromley LM, Woolf CJ. Preoperative morphine pre-empts postoperative pain. Lancet 1993; 342: 73–5 Tverskoy M, Oz Y, Isakson A, Finger J, Bradley EL jr, Kissin I. Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg 1994; 78: 205–9
Postoperative cognitive deficit in the elderly surgical patient Editor,—We read with interest the review article on postoperative cognitive deficit in the elderly surgical patient.1 We agree with the authors that cognitive dysfunction after surgery and anaesthesia is common and persistent, and should be considered seriously. Among other risk factors, cardiopulmonary bypass (CPB) has been blamed for these neurological and neuropsychological deficits. The incidence of neurological abnormalities is quoted to be as high as 61% in the early postoperative period and 17% at the time of discharge from hospital. The incidence of neuropsychological deficits is even higher: 79% in the postoperative period and 38% at the time of discharge.1 The incidence of frank stroke is reported to be as high as 4.8–5.2% overall and in patients who are more than 75 yr of age it approaches 9%.2 In recent years, nuclear medicine has made tremendous advances in studying physiological changes in the brain. Positron emission tomography (PET) and single photon emission computerized tomography (SPECT) provide information on cerebral metabolism and regional cerebral blood flow, respectively. These techniques have been used successfully in studying pathophysiology in patients with neurological and psychiatric illnesses such as Alzheimer’s disease, dementia, Parkinson’s disease and stroke.3 They are also being used in oncology for diagnosis, determining prognosis and guiding treatment. More recently, PET and SPECT scanning have been found to be useful in studying the effects of CPB on cerebral function in patients undergoing cardiac surgery.4 It would be interesting to see if it
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is possible to demonstrate any changes in cerebral metabolism and regional cerebral blood flow in CPB patients and to see how these variables are related to neuropsychological function. R. H. Rehman Department of Anaesthesia P. Kemp Department of Nuclear Medicine Southampton General Hospital Southampton, UK 1 Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth 1998; 81: 449–62 2 Breuer AC, Furlan AJ, Hanson MR, et al. Central nervous system complications of coronary bypass graft surgery: prospective analysis of 421 patients. Stroke 1983; 14: 682–7 3 Ell PJ, Costa DC The role of nuclear medicine in neurology and psychiatry. Curr Opin Neurol Neurosurg 1992; 5: 863–9 4 Marochnick S, Alexandrov AV, Anthone D, Lewin C, Caldwell CB, Pullicino PM. Feasibility of SPECT for studies of brain perfusion during cardiopulmonary bypass. J Neuroimaging 1996; 6: 243–5
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