1447
opioids alone has been associated with inadequate pain relief, tachyphylaxis with repeated doses, and considerable systemic absorption resulting in nausea, sedation, respiratory depression, pruritus, and effects on the newborn baby. Pethidine (meperidine) has shown more promise when used epidurally, but this effect
epidural administration,2,3
use
of
may be due to the weak local anaesthetic action of this
drug as much as to its opioid activity4 Duration of analgesia from a single dose is unpredictable,s but pethidine may have a role as a single large dose bolus, to be followed by local anaesthetic top-ups as
required ,6 There is more cause for optimism when opioids and
local anaesthetics are used in combination, because their complementary action means that each drug spares the other. The widest experience has been with the pethidine derivative fentanyl. Too short-acting for one-off use, this drug can be given in doses of 50 or 100 ug added to each top-up of bupivacaine/ or by addition to a continuous infusion at a concentration of 2-2-5 Ilg/ml.8-11 At its simplest, addition of fentanyl in this way allows for a halving of the concentration of bupivacaine without any diminution of pain relief.12 This, in turn, leads to a considerable reduction in the degree of motor block. Perhaps even more interesting is the ability of this combination to hasten the onset of analgesia,l1,13 prolong the effect of each top-Up/,13 and improve the relief of perineal pain.14 Reduction in local anaesthetic concentration might diminish the risk of hypotension and instrumental delivery. The newer opioids alfentanil and sufentanil have also been tried. Sufentanil, in particular, looks promising-a dose as low as 7-5 Ilg speeds bupivacaine onset time and significantly improves quality and duration of from a single top-up when added to boluses of 0-125% bupivacaine.1s Epidural diamorphine is commonly used for postoperative analgesia. The pharmacokinetic profile of this agent is more encouraging than that of morphine, and one study showed that, when given with 0-25%
analgesia
bupivacaine as a single 5 mg bolus, diamorphine considerably enhances the analgesia produced by a subsequent bupivacaine infusion.16 Diamorphine is also beneficial when used as an adjunct by infusion, 25 ug/ml being more effective than 2 Ilg/ml of fentanyl at relieving pain, especially in the second stage of labour.8 These benefits are not achieved without cost. Generalised pruritus is a well-recognised side-effect of epidural opioids, with a frequency as high as 70% when doses of diamorphine as large as 5 mg are used.16 Patients may also experience nausea, but both of these effects become less troublesome with low doses (eg,
diamorphine 0-2 mg/hour or fentanyl 15 pg/hour8), which seem to be as effective as the high doses used in earlier studies. Lipid-soluble opioids cross the placenta, and although the crude measure of the Apgar score seems unaffected, more work is needed with sensitive neurobehavioural scores to assess the
effect on the baby. The delayed respiratory depression occasionally seen with epidural morphine has not yet been observed with the newer agents, but the possibility must be borne in mind; systemic and epidural opioids should never be given in combination. Finally, the mixing of non-standard drug combinations by doctors or midwives increases the risk of administering the wrong dose or the wrong drug, and it may be that hospital pharmacies should be encouraged to prepare the mixtures under controlled conditions. Despite these few reservations the judicious use of opioids and local anaesthetics in combination can improve analgesia for labouring mothers even further. Opioids in labour are making a comeback. 1. Husemeyer RP, O’Connor MC, Davenport HT. Failure of epidural morphine to relieve pain in labour. Anaesthesia 1980; 35: 161-63. 2. Heytens L, Cammu H, Camu F. Extradural analgesia during labour using alfentanil. Br J Anaesth 1987; 59: 331-37. 3. Carrie LE, O’Sullivan GM, Seegobin R. Epidural fentanyl in labour. Anaesthesia 1981; 36: 965-69.
Husemeyer RP, Davenport HT, Cummings AJ, Rosankiewicz JR. Comparison of epidural and intramuscular pethidine for analgesia in labour. Br J Obstet Gynaecol 1981; 88: 711-17 5. Skjoldebrand A, Garle M, Gustafsson LL, Johansson H, Lunell NO, Rane A. Extradural pethidine with and without adrenaline during labour: wide variation in effect. Br J Anaesth 1982; 54: 415-20. 6. Baraka A, Maktabi M, Noueihid R. Epidural meperidine-bupivacaine for obstetric analgesia. Anaesth Analg 1982; 61: 652-56. 7. Celleno D, Capogna G. Epidural fentanyl plus bupivacaine 0·25% for labor: analgesic effects. Can J Anaesth 1988; 35: 375-78. 8. Enever GR, Noble HA, Kolditz D, Valentine S, Thomas TA. Epidural infusion of diamorphine with bupivacaine in labour. Anaesthesia 1991;
4.
46: 169-73. 9. Chestnut DH, Laszewski LJ, Pollack KL, Bates JN, Manago NK, Choi WW. Continuous epidural infusion of 0·0625% bupivacaine— 0·0002% fentanyl during the second stage of labor. Anesthesiology 1990; 72: 613-18. 10. Chestnut DH, Owen CL, Bates JN, Ostman LG, Choi WW, Geiger MW. Continuous infusion epidural analgesia during labor: a randomized, double-blind comparison of 0·0625% bupivacaine/ 0 0002% fentanyl versus 0·125% bupivacaine. Anesthesiology 1988; 68: 754-59. 11. Jones G, Paul DL, Elton RA, McClure JH. Comparison of bupivacaine and bupivacaine with fentanyl in continuous extradural analgesia during labour. Br J Anaesth 1989; 63: 254-59. 12. Yau G, Gregory MA, Gin T, Bogod DG, Oh TE. The addition of fentanyl to epidural bupivacaine in first stage labour Anaesth Intensive Care 1990; 18: 532-35. 13. Justins DM, Francis D, Houlton PG, Reynolds F. A controlled trial of extradural fentanyl in labour. Br J Anaesth 1982; 54: 409-14. 14. Reynolds F, O’Sullivan G. Epidural fentanyl and perineal pain in labour. Anaesthesia 1989; 44: 341-44. 15. Van Steenberge A, Debroux HC, Noorduin H. Extradural bupivacaine with sufentanil for vaginal delivery: a double-blind trial. Br J Anaesth 1987; 59: 1518-22. 16. McGrady EM, Brownhill DK, Davis AG. Epidural diamorphine and bupivacaine m labour. Anaesthesia 1989; 44: 400-03.
The
bleeding time
How should we react to a rigorous scientific reappraisal of a time-honoured clinical test? The skin
bleeding time, first described 90 years ago,l provides a clinical assessment of the platelet and small vessel contribution to haemostasis. This test is used in the detection of von Willebrand’s disease, some platelet function disorders, and as a predictor of clinically significant bleeding at operation or biopsy in certain diseases. We know that the result is affected by packed
1448
cell volume,
by uraemia, and by many drugs, especially aspirin; it may also be influenced by hypertension and by a raised serum bilirubin. Rodgers and Levin2have now re-examined more than 1000 published studies of the bleeding time. The conclusion from their thorough mathematical scrutiny is clear; there is very little scientific evidence to support the use of the bleeding time as a diagnostic test or as a predictor of clinically significant bleeding in individual patients. They review the much cited work of Harker and Slichter3concerning the relation between bleeding time and platelet count and question its general applicability. Although they concede that standardisation of the method would be in everyone’s interest, they could find no evidence that newer versions produce any improvement in the low sensitivity and specificity of the test. In the assessment of patients who may have a bleeding disorder, by far the most important thing is an accurate and complete history, including a drug history and details of the family. If the history is not informative and platelet count and coagulation tests are normal, a skin bleeding time is probably superfluous. Perhaps clinicians are reassured by watching haemostasis in action; if the wound stops bleeding before one’s eyes and one can see the strands of fibrin drawn out by the filter paper then it is tempting to believe that there should be no bleeding after, say, a renal biopsy. The evidence is very clear that this conclusion could be seriously wrong. Used judiciously,4 the bleeding time deserves to remain as part of the assessment of individual patients with histories suggestive of bleeding disorders. The test requires very little equipment and no laboratory facilities and therefore has a place in epidemiological field work. Careful prospective trials are still needed to determine whether the bleeding time can be a useful predictor of clinically significant bleeding; the variables affecting the test are known and welldesigned studies should give a clear answer. 1. Milian MG. Technique pour l’étude de la coagulation du sang. Bull Mem Soc Med Hop Paris 1901; 18: 777-83 (cited in ref 2). 2. Rodgers RPC, Levin J. A critical review of the bleeding time. Semin Thromb Hemost 1990; 16: 1-20. 3. Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med 1972; 287: 155-59. 4. Hamblin TJ. What about the bleeding time? Br Med J 1985; 291: 91.
Pulling British undergraduate medical education into the twentieth century At the May meeting of the General Medical Council (GMC), the education committee presented new directions for undergraduate medical education. Recognising that the 1980 Recommendations on Basic Medical Education1 have had very little impact, the GMC has approved a new set of proposals for consultation with the licensing bodies. The main thrusts are towards more integrated (and thus relevant, effective, and interesting) teaching, with
various threads specified throughout the five years of medical school, and towards a core-plus-options approach, to get away from the straitjacket2 of contemporary medical education. Although a few British medical schools have tried to develop curricula based on twentieth century needs and pedagogy, undergraduate medical education in the UK is still driven largely by tradition. The new proposals will ensure that the big departments in both basic science and clinical disciplines play a part determined less by traditional clout and more by educational need. The implications for some medical schools are greater than for others. They are perhaps greatest for the preclinical faculties in some of the older universities, who keep themselves very separate from the world of patients and "real" medicine. There are far more overwhelming implications for the GMC itself. Responsibility for implementing its education function—covering all stages of medical education (undergraduate, postgraduate, continuing) -is devolved to six administrators. Education took up 259 372 (49%) of the GMC’s annual expenditure for the year ending December, 1989. By comparison, the Association of American Medical Colleges (the nearest comparable body as regards education in the USA), which is funded mainly by dues from the medical schools and teaching hospitals, spent over$6 million in 1989/90 on educational matters and accreditation.3So the GMC must obtain the necessary skills and manpower to pursue this initiative, if necessary seeking to review its funding structure. Ordinary registered medical practitioners, whose annual fees are a major source of income for the GMC, may well ask why they have, in effect, to fund the reform of the medical schools. Educationists will be quick to realise an inevitable implication of the variety of medical education produced by a system of core courses and optionsthe need for a national assessment procedure. Such an arrangement will be required to monitor schools’ standards overall and also to guarantee individuals’ core knowledge and skills in the public interest. A national examination could be conducted either as an entry requirement to the final MB or as an additional prerequisite to registration. In the absence of a credible organisation that could represent all medical schools for this purpose, the GMC would need to take on an additional role. Contemporary final medical examinations, occasionally inspected for the GMC by a group of senior academics, have been criticised for being uninspired, inappropriate,4 and even incompetent. Thus most schools continue to use "long cases" as key components of finals,s despite overwhelming evidence that clinical skills of candidates vary considerably between cases.6Reliance on a single long case is thus unjust and unwise. A central examination body could help to devise the type of innovative certification procedures that are being developed in Canada,for
example.
opioids alone has been associated with inadequate pain relief, tachyphylaxis with repeated doses, and considerable systemic absorption resulting in nausea, sedation, respiratory depression, pruritus, and effects on the newborn baby. Pethidine (meperidine) has shown more promise when used epidurally, but this effect
epidural administration,2,3
use
of
may be due to the weak local anaesthetic action of this
drug as much as to its opioid activity4 Duration of analgesia from a single dose is unpredictable,s but pethidine may have a role as a single large dose bolus, to be followed by local anaesthetic top-ups as
required ,6 There is more cause for optimism when opioids and
local anaesthetics are used in combination, because their complementary action means that each drug spares the other. The widest experience has been with the pethidine derivative fentanyl. Too short-acting for one-off use, this drug can be given in doses of 50 or 100 ug added to each top-up of bupivacaine/ or by addition to a continuous infusion at a concentration of 2-2-5 Ilg/ml.8-11 At its simplest, addition of fentanyl in this way allows for a halving of the concentration of bupivacaine without any diminution of pain relief.12 This, in turn, leads to a considerable reduction in the degree of motor block. Perhaps even more interesting is the ability of this combination to hasten the onset of analgesia,l1,13 prolong the effect of each top-Up/,13 and improve the relief of perineal pain.14 Reduction in local anaesthetic concentration might diminish the risk of hypotension and instrumental delivery. The newer opioids alfentanil and sufentanil have also been tried. Sufentanil, in particular, looks promising-a dose as low as 7-5 Ilg speeds bupivacaine onset time and significantly improves quality and duration of from a single top-up when added to boluses of 0-125% bupivacaine.1s Epidural diamorphine is commonly used for postoperative analgesia. The pharmacokinetic profile of this agent is more encouraging than that of morphine, and one study showed that, when given with 0-25%
analgesia
bupivacaine as a single 5 mg bolus, diamorphine considerably enhances the analgesia produced by a subsequent bupivacaine infusion.16 Diamorphine is also beneficial when used as an adjunct by infusion, 25 ug/ml being more effective than 2 Ilg/ml of fentanyl at relieving pain, especially in the second stage of labour.8 These benefits are not achieved without cost. Generalised pruritus is a well-recognised side-effect of epidural opioids, with a frequency as high as 70% when doses of diamorphine as large as 5 mg are used.16 Patients may also experience nausea, but both of these effects become less troublesome with low doses (eg,
diamorphine 0-2 mg/hour or fentanyl 15 pg/hour8), which seem to be as effective as the high doses used in earlier studies. Lipid-soluble opioids cross the placenta, and although the crude measure of the Apgar score seems unaffected, more work is needed with sensitive neurobehavioural scores to assess the
effect on the baby. The delayed respiratory depression occasionally seen with epidural morphine has not yet been observed with the newer agents, but the possibility must be borne in mind; systemic and epidural opioids should never be given in combination. Finally, the mixing of non-standard drug combinations by doctors or midwives increases the risk of administering the wrong dose or the wrong drug, and it may be that hospital pharmacies should be encouraged to prepare the mixtures under controlled conditions. Despite these few reservations the judicious use of opioids and local anaesthetics in combination can improve analgesia for labouring mothers even further. Opioids in labour are making a comeback. 1. Husemeyer RP, O’Connor MC, Davenport HT. Failure of epidural morphine to relieve pain in labour. Anaesthesia 1980; 35: 161-63. 2. Heytens L, Cammu H, Camu F. Extradural analgesia during labour using alfentanil. Br J Anaesth 1987; 59: 331-37. 3. Carrie LE, O’Sullivan GM, Seegobin R. Epidural fentanyl in labour. Anaesthesia 1981; 36: 965-69.
Husemeyer RP, Davenport HT, Cummings AJ, Rosankiewicz JR. Comparison of epidural and intramuscular pethidine for analgesia in labour. Br J Obstet Gynaecol 1981; 88: 711-17 5. Skjoldebrand A, Garle M, Gustafsson LL, Johansson H, Lunell NO, Rane A. Extradural pethidine with and without adrenaline during labour: wide variation in effect. Br J Anaesth 1982; 54: 415-20. 6. Baraka A, Maktabi M, Noueihid R. Epidural meperidine-bupivacaine for obstetric analgesia. Anaesth Analg 1982; 61: 652-56. 7. Celleno D, Capogna G. Epidural fentanyl plus bupivacaine 0·25% for labor: analgesic effects. Can J Anaesth 1988; 35: 375-78. 8. Enever GR, Noble HA, Kolditz D, Valentine S, Thomas TA. Epidural infusion of diamorphine with bupivacaine in labour. Anaesthesia 1991;
4.
46: 169-73. 9. Chestnut DH, Laszewski LJ, Pollack KL, Bates JN, Manago NK, Choi WW. Continuous epidural infusion of 0·0625% bupivacaine— 0·0002% fentanyl during the second stage of labor. Anesthesiology 1990; 72: 613-18. 10. Chestnut DH, Owen CL, Bates JN, Ostman LG, Choi WW, Geiger MW. Continuous infusion epidural analgesia during labor: a randomized, double-blind comparison of 0·0625% bupivacaine/ 0 0002% fentanyl versus 0·125% bupivacaine. Anesthesiology 1988; 68: 754-59. 11. Jones G, Paul DL, Elton RA, McClure JH. Comparison of bupivacaine and bupivacaine with fentanyl in continuous extradural analgesia during labour. Br J Anaesth 1989; 63: 254-59. 12. Yau G, Gregory MA, Gin T, Bogod DG, Oh TE. The addition of fentanyl to epidural bupivacaine in first stage labour Anaesth Intensive Care 1990; 18: 532-35. 13. Justins DM, Francis D, Houlton PG, Reynolds F. A controlled trial of extradural fentanyl in labour. Br J Anaesth 1982; 54: 409-14. 14. Reynolds F, O’Sullivan G. Epidural fentanyl and perineal pain in labour. Anaesthesia 1989; 44: 341-44. 15. Van Steenberge A, Debroux HC, Noorduin H. Extradural bupivacaine with sufentanil for vaginal delivery: a double-blind trial. Br J Anaesth 1987; 59: 1518-22. 16. McGrady EM, Brownhill DK, Davis AG. Epidural diamorphine and bupivacaine m labour. Anaesthesia 1989; 44: 400-03.
The
bleeding time
How should we react to a rigorous scientific reappraisal of a time-honoured clinical test? The skin
bleeding time, first described 90 years ago,l provides a clinical assessment of the platelet and small vessel contribution to haemostasis. This test is used in the detection of von Willebrand’s disease, some platelet function disorders, and as a predictor of clinically significant bleeding at operation or biopsy in certain diseases. We know that the result is affected by packed
1448
cell volume,
by uraemia, and by many drugs, especially aspirin; it may also be influenced by hypertension and by a raised serum bilirubin. Rodgers and Levin2have now re-examined more than 1000 published studies of the bleeding time. The conclusion from their thorough mathematical scrutiny is clear; there is very little scientific evidence to support the use of the bleeding time as a diagnostic test or as a predictor of clinically significant bleeding in individual patients. They review the much cited work of Harker and Slichter3concerning the relation between bleeding time and platelet count and question its general applicability. Although they concede that standardisation of the method would be in everyone’s interest, they could find no evidence that newer versions produce any improvement in the low sensitivity and specificity of the test. In the assessment of patients who may have a bleeding disorder, by far the most important thing is an accurate and complete history, including a drug history and details of the family. If the history is not informative and platelet count and coagulation tests are normal, a skin bleeding time is probably superfluous. Perhaps clinicians are reassured by watching haemostasis in action; if the wound stops bleeding before one’s eyes and one can see the strands of fibrin drawn out by the filter paper then it is tempting to believe that there should be no bleeding after, say, a renal biopsy. The evidence is very clear that this conclusion could be seriously wrong. Used judiciously,4 the bleeding time deserves to remain as part of the assessment of individual patients with histories suggestive of bleeding disorders. The test requires very little equipment and no laboratory facilities and therefore has a place in epidemiological field work. Careful prospective trials are still needed to determine whether the bleeding time can be a useful predictor of clinically significant bleeding; the variables affecting the test are known and welldesigned studies should give a clear answer. 1. Milian MG. Technique pour l’étude de la coagulation du sang. Bull Mem Soc Med Hop Paris 1901; 18: 777-83 (cited in ref 2). 2. Rodgers RPC, Levin J. A critical review of the bleeding time. Semin Thromb Hemost 1990; 16: 1-20. 3. Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med 1972; 287: 155-59. 4. Hamblin TJ. What about the bleeding time? Br Med J 1985; 291: 91.
Pulling British undergraduate medical education into the twentieth century At the May meeting of the General Medical Council (GMC), the education committee presented new directions for undergraduate medical education. Recognising that the 1980 Recommendations on Basic Medical Education1 have had very little impact, the GMC has approved a new set of proposals for consultation with the licensing bodies. The main thrusts are towards more integrated (and thus relevant, effective, and interesting) teaching, with
various threads specified throughout the five years of medical school, and towards a core-plus-options approach, to get away from the straitjacket2 of contemporary medical education. Although a few British medical schools have tried to develop curricula based on twentieth century needs and pedagogy, undergraduate medical education in the UK is still driven largely by tradition. The new proposals will ensure that the big departments in both basic science and clinical disciplines play a part determined less by traditional clout and more by educational need. The implications for some medical schools are greater than for others. They are perhaps greatest for the preclinical faculties in some of the older universities, who keep themselves very separate from the world of patients and "real" medicine. There are far more overwhelming implications for the GMC itself. Responsibility for implementing its education function—covering all stages of medical education (undergraduate, postgraduate, continuing) -is devolved to six administrators. Education took up 259 372 (49%) of the GMC’s annual expenditure for the year ending December, 1989. By comparison, the Association of American Medical Colleges (the nearest comparable body as regards education in the USA), which is funded mainly by dues from the medical schools and teaching hospitals, spent over$6 million in 1989/90 on educational matters and accreditation.3So the GMC must obtain the necessary skills and manpower to pursue this initiative, if necessary seeking to review its funding structure. Ordinary registered medical practitioners, whose annual fees are a major source of income for the GMC, may well ask why they have, in effect, to fund the reform of the medical schools. Educationists will be quick to realise an inevitable implication of the variety of medical education produced by a system of core courses and optionsthe need for a national assessment procedure. Such an arrangement will be required to monitor schools’ standards overall and also to guarantee individuals’ core knowledge and skills in the public interest. A national examination could be conducted either as an entry requirement to the final MB or as an additional prerequisite to registration. In the absence of a credible organisation that could represent all medical schools for this purpose, the GMC would need to take on an additional role. Contemporary final medical examinations, occasionally inspected for the GMC by a group of senior academics, have been criticised for being uninspired, inappropriate,4 and even incompetent. Thus most schools continue to use "long cases" as key components of finals,s despite overwhelming evidence that clinical skills of candidates vary considerably between cases.6Reliance on a single long case is thus unjust and unwise. A central examination body could help to devise the type of innovative certification procedures that are being developed in Canada,for
example.
