- Email: [email protected]
Awareness of awareness during general anaesthesia
COMMENTARY
documented episodes of cerebral malaria and each used a paired case-control design to look for cognitive impairments that could be associated with the previous illness. In the Gambian study,3 the proportion of children with a cognitive or sensorimotor disability did not differ between cases and controls. In a more recent study from Kenya,4 there were significantly more children with cognitive impairment among the cases (12/87) than among the controls (3/87). What is to be made of these discrepant findings? Both groups used a battery of tests of intellectual, sensorimotor, and behavioural functions that had been piloted locally and adapted to the local language and culture. The tests were given on two separate occasions in the home of each individual. Differences in the actual tests applied could have affected the results. Moreover, the children in the Gambian study were older (mean age 42 months) than those in the Kenyan study (mean age 26 months) at the time of the original episode of cerebral malaria. Another important difference between the studies is that the Gambian investigators included only children who had no detectable neurological sequelae at the end of their original illness. Among the 75 children in the Kenyan study without initial sequelae, five were cognitively impaired at the time of the follow-up assessment, compared with three of the 87 controls; five of 12 children with neurological sequelae at the end of their original illness had no detectable neurological or cognitive deficit a few years later. To know for certain the risk and extent of cognitive impairment in children who recover from cerebral malaria with no detectable neurological deficit, larger studies would be needed. These are difficult to achieve. The impressive studies described above required the long-term presence of research teams and close and continuing access to communities. Meanwhile, there are enough reasons to do all that is possible to prevent cerebral malaria and, when it occurs, to treat it promptly and effectively. The above studies, and others observing the gross neurological sequelae of cerebral malaria,5,6 have identified features of the original illness that are prognostic of later cerebral impairment; among these factors, depth of coma and repeated or prolonged seizures have emerged in almost all studies as being prognostically important. Do seizures of themselves contribute to brain damage, or merely reflect the severity of underlying abnormality? This question, with its important implications for the management of cerebral malaria, can be determined only by an intervention specifically directed against seizures. But what is an effective measure for prevention of seizures in children with cerebral malaria? In this issue of The Lancet, Jane Crawley and colleagues report a trial of one such measure in children with cerebral malaria admitted to a district hospital in Kilifi, Kenya. In a double-blind study, they randomly allocated 340 children phenobarbital 20 mg/kg or placebo by intramuscular injection, then treated all with appropriate antimalarial, antibiotic, and anticonvulsant drugs and supportive therapy. They recorded clinical developments, including seizures during the illness, and outcomes. An interim analysis, the results of which were not disclosed to the investigators, showed that children in the phenobarbital group had significantly fewer seizures and neurological sequelae than the placebo group; a trend of more deaths in the phenobarbital group did not reach statistical significance. Had the study been stopped accordingly at this point, phenobarbital 20 mg/kg may have been 672
recommended throughout Africa as being beneficial against convulsions in cerebral malaria, with potentially disastrous consequences. The monitors in this study correctly continued the study, which then showed a significantly higher mortality in the phenobarbital group than in the placebo group. Was the excess of deaths due to phenobarbital, or to the additional effect of three or more doses of diazepam in some of these patients? The study cannot provide an answer, since those children needing additional diazepam are likely to have had more severe disease, and may have been more susceptible to phenobarbital for that reason alone. Studies are still needed to guide the use of anticonvulsants in cerebral malaria. Whether smaller doses of phenobarbital, or alternative drug(s), are evaluated, numbers must be large enough to detect an effect on seizures and on mortality and sequelae. Numbers must be even larger if patients are to be followed over several years to detect benefit against subtle impairments that may persist in the long term. Malcolm E Molyneux Wellcome Trust Research Laboratories, College of Medicine, University of Malawi, Box 30096, Blantyre 3, Malawi; and School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, UK 1 2 3
4
5
6
Brewster DR, Kwiatkowski D,White NJ. Neurological sequelae of cerebral malaria in children. Lancet 1990; 336: 1039–43. Bondi FS.The incidence and outcome of neurological abnormalities in childhood cerebral malaria. Trans R Soc Trop Med Hyg 1992; 86: 17–19. Muntendam AH, Jaffar S, Bleichrodt N, van Hensbroek MB. Absence of neuropsychological sequelae following cerebral malaria in Gambian children. Trans R Soc Trop Med Hyg 1996; 90: 391–94. Holding PA, Stevenson J, Peshu N, Marsh K. Cognitive sequelae of severe malaria with impaired consciousness. Trans R Soc Trop Med Hyg 1999; 93: 529–34. Molyneux ME, Taylor TE,Wirima JJ, Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 1989; 71: 441–59. Van Hensbroek MB, Palmer A, Jaffar S, Schneider G, Kwiatkowski D. Residual neurological sequelae after childhood cerebral malaria. J Pediatr 1997; 131: 125–29.
Awareness of awareness during general anaesthesia See page 707 Io non mori’, e non rimasi vivo; Pensa omai per te, s’hai fior d’ingegno, Qual io divenni, d’uno e d’altro privo. [Neither did I die, nor did I remain alive; Imagine yourself, if your spirit is fine, what I came to be, deprived of both.] —Dante, Inferno XXXIV, 25–27.
Within the indeterminate state called anaesthesia, awareness can persist or re-emerge. Semantically a contradiction (unawareness is part of the definition of anaesthesia), logically a paradox, awareness during general anaesthesia is a pitfall for the anaesthetist, a horror for the patient, an invitation for the prosecutor. Since awareness during general anaesthesia came into being on the very days that inhalational anaesthetics were inaugurated—the first patients given nitrous oxide by Horace Wells in 1845 and ether by William TG Morton in 1846 were “half-awake” and reported feeling pain during surgery—the topic of Rolf Sandin and colleagues’ report of their large and thorough study in today’s Lancet is hardly novel. Wherein lies the interest in this paper?
THE LANCET • Vol 355 • February 26, 2000
COMMENTARY
In 1997 and 1998 Sandin and colleagues questioned almost all (97%) surgical patients aged over 15 years in two Swedish hospitals about explicit recall of intraoperative events (ie, awareness during anaesthesia). Together these patients had undergone a wide range of procedures, and nearly all had received inhalational anaesthetics (two-thirds of them sevoflurane, a third isoflurane). Sandin and colleagues found 18 cases of awareness among nearly 12 000 patients. How does this rate of 0·15% compare with previous reports? Measurements depend on what is measured and how it is measured. Sandin restricted his inquiry to explicit forms of memory—ie, conscious awareness with spontaneous recall of events. Dreaming and implicit memory (the recondite realm of unconscious perceptions, learning, and absorption of “advertising” messages during anaesthesia1) were not explored. Hypnotists can extract recollections of intraoperative events in a high proportion of patients (four out of ten patients in a famous case-series reported by Levinson2 who, however, could not repeat the feat 30 years later). Sandin and colleagues did not use hypnosis. Patients were interviewed on leaving the recovery room, 1–3 days later, and 1–2 weeks later. The first interview detected only half the cases of awareness eventually identified. Although other anaesthetists fear that “it is easy for patients to imagine more than they actually experienced if considerable time elapsed between the anaesthetic and the [interview]”,3 Sandin’s findings suggest that accurate explicit recall of intraoperative events may be delayed. The overall percentage of people reporting awareness in Sandin and colleagues’ paper is lower than that found in previous surveys in similar mixed surgical settings.4–6 The Swedish surgical cohort did not include cardiacsurgery patients (whose brains may be awake because they are sometimes anaesthetised such as to spare the heart) but it included trauma victims and patients who underwent caesarean sections (groups also classically semi-dormient, the former because anaesthetic agents, commonly cardiovascular depressants, may worsen shock, the latter so that strongly crying babies are extracted). The finding of only one case of awareness among the caesarean group may be because the women were put under adequate general anaesthesia7 or because most of them were delivered under spinal or epidural anaesthesia—ie, under a state of deliberate painless awareness. The curare-like drugs were introduced in the 1940s and 1950s and ever since the publication of the first reports of awake-paralysed patients (those who receive muscle relaxants together with inadequate amounts of anaesthetic drugs),8 it has generally been accepted that “spontaneous recall” during general anaesthesia is confined almost entirely to such patients.9 However, non-paralysed patients may be aware-awake too; in Sandin’s study patients not given muscle relaxants had a lower, albeit not zero, risk of awareness than did those given neuromuscular blocking agents (0·18% vs 0·10%). Delayed neurotic symptoms (post-traumatic stress disorder) can follow awareness during general anaesthesia.10 As recognised since the first reports of this complication after general anaesthesia 25 years ago, neurotic symptoms in the Swedish surgical patients who reported awareness during general anaesthesia were more likely among those who were paralysed than among those who were not paralysed by neuromuscular
THE LANCET • Vol 355 • February 26, 2000
blocking agents, and when the patient had experienced intense pain while under anaesthesia. A striking finding in Sandin’s study is the relation between delayed neurotic symptoms and the patient’s inability to understand what was actually happening during undesired wakefulness. This point raises the question of whether the possibility of awareness should be discussed with the patient preoperatively to reduce the likelihood of neurotic symptoms, or whether doing so would worry too many patients unnecessarily. With the anaesthetist’s explanations and reassurance, reiterated until the patient was satisfied, neuropsychiatric symptoms in all of the patients resolved within 3 weeks, without psychiatric support. Patients in other reports have been less lucky,9 perhaps because explanation and reassurance were not as timely. Since most cases of awareness are due to faulty apparatus of technique,11 prevention justifiably focuses on equipment and training. In addition, various monitoring devices have been proposed for assessment of the state of awareness, or the depth of anaesthesia, to find out whether a patient is not really asleep when he or she ought to be.3 Sandin and colleagues’ findings cast doubt on the belief that one of these methods —namely, monitoring of expiratory anaesthetic-gas concentration—helps avoid awareness. And they suggest caution before adopting novel neurophysiological monitoring techniques allegedly capable of reducing the likelihood of awareness. Assessment of the reliability of these methods would require huge clinical trials. When it comes to rare events, evidence-based anaesthesia is hard to achieve. Another accepted dogma challenged by Sandin and colleagues’ findings is that benzodiazepines do not afford protection from awareness, and they rightly question the use of these drugs to prevent patients from remembering awareness should it occur. That no case of awareness in Sandin’s study was due to equipment failure is a favourable reflection of anaesthetic practice at the two Swedish hospitals. Another commendable feature of practice there, which reflects concern for patients’ comfort, is that the anaesthetists routinely ask patients about awareness. Awareness may be accepted by anaesthetists as an inevitable occurrence, but it is not acceptable to the patient, even if he is himself an anaesthetist.12 Awareness of awareness is the first step out. Bruno Simini Ospedale, 55100 Lucca, Italy 1 Anonymous. Advertising during anaesthesia? Lancet 1986; ii: 1019–20. 2 Levinson BW. States of awareness during general anaesthesia. Br J Anaesth 1965; 37: 544–46. 3 Bailey AR, Jones JG. Patients’ memories of events during general anaesthesia. Anaesthesia 1997; 52: 460–76. 4 Liu WHD, Thorp TAS, Graham SG, Aitkenhead AR. Incidence of awareness with recall during general anaesthesia. Anaesthesia 1991; 46: 435–37. 5 Sandin R, Nordström O. Awareness during total iv anaesthesia. Br J Anaesth 1993; 71: 782–87. 6 Ranta SO-V, Laurila R, Saario J, Ali-Melkkilä T, Hynynen M. Awareness with recall during general anesthesia: incidence and risk factors. Anesth Analg 1998; 86: 1084–89. 7 Reynolds F. Anaesthesia for caesarean section: no need for nightmares. Anesthesia 1986; 41: 652. 8 Anonymous. Awareness during anaesthesia. Lancet 1973; ii: 1305. 9 Aitkenhead AR. Awareness during anaesthesia: when is an anaesthetic not an anaesthetic? Can J Anaesth 1996; 43: 206–11.
673
COMMENTARY 10 Schwender D, Kunze-Kronawitter H, Dietrich P, Klasing S, Forst H, Madler C. Perceptions, emotions, cognition and reactions. Br J Anaesth 1998; 80: 133–39. 11 Brighouse D, Norman J. To wake in fright. BMJ 1992; 304: 1327–28. 12 Peduto VA, Silvetti L, Piga M. [An anaesthetized anaesthetist tells his experience of waking up accidentally during an operation]. Minerva Anestesiol 1994; 60: 1–5.
Jelly-beans, only a colourful distraction from gestational glucose-challenge tests In 1993 John Jarrett questioned the very existence of gestational diabetes,1 and today the debate on whether pregnant women should be screened for glucose intolerance continues.2 Those against universal screening point to the lack of randomised controlled studies showing any tangible benefit in terms of perinatal mortality and morbidity derived from screening for or treatment of glucose intolerance.3,4 Meanwhile the screening process itself, they argue, creates an obstetric environment that promotes unnecessary operative deliveries for women whose only risk factor is asymptomatic hyperglycaemia.5 The opponents of screening are commonly epidemiologists and publichealth physicians who live their life according to the credo of evidence-based medicine, and as a group are rarely left holding the macrosomic baby or dealing with a difficult shoulder delivery. Those in favour are more likely to be obstetric physicians with a wealth of anecdotal experience of dealing with the emotional aftermath of stillbirth and birth trauma, which, rightly or wrongly, have been attributed to gestational diabetes. For these obstetricians, not to screen is tantamount to negligence. They highlight the point that the higher the maternal blood-glucose concentrations in women with pre-gestational diabetes, the stronger the association with perinatal mortality and morbidity, childhood obesity, and diabetes in early adult life.6–8 With a certain leap of faith they extrapolate downwards to lesser degrees of glucose intolerance, to conclude that there is a continuum of risk between maternal blood-glucose concentrations and adverse pregnancy outcome that extends into the normal glycaemic range. So what next? The answer has to be to sit back, be patient, and wait until 2003, when the results of the HAPO (Hyperglycaemia Adverse Pregnancy Outcome) Study, funded by the US National Institutes of Health, become available.9 This study will involve 16 centres, three continents, and 25 000 unselected pregnant women who will undergo a 75 g oral glucose-tolerance test at 28 weeks of pregnancy. Only women who fulfil the WHO criteria for diabetes will be treated, so all lesser degrees of hyperglycaemia can be correlated with shortterm variables of pregnancy outcome. Follow-up studies will allow the examination of the medium-term and long-term effects of maternal hyperglycaemia on the future health of the mother and her child. Only after this study will the threshold of maternal blood-glucose concentration that carries no added risk to pregnancy be known. Until then no effort should be made to rewrite and redefine the screening and diagnostic criteria for gestational diabetes. It is against this background that one needs to consider the recent paper by Michael Lamar and colleagues10 on the use of jelly beans for screening for gestational diabetes. Lamar and colleagues purport that a fistful of 28 jelly beans (nine colours and ten flavours) 674
is a more mother-friendly screening test for gestational diabetes than the usual 50 g oral glucose drink, because it causes less nausea, headache, and sweating. They compared the 1 h serum glucose value after a 50 g oral glucose drink with that after a 50 g glucose load as found in 28 jelly beans. 136 women, who were 24–28 weeks pregnant, participated in both screening tests, and all subsequently underwent a diagnostic 3 h oral glucose-tolerance test.11 Of the 136 women five had gestational diabetes; two of these had screened positive with the jelly-bean test and four with the glucose drink, giving sensitivity values for these screening tests of 40% and 80%, respectively. The positive predictive values of these two tests would be expected to become even more discrepant among populations with higher prevalence rates of gestational diabetes. Hence the jelly-bean jar should remain firmly shut, and any temptation to develop confectionery screening should be discouraged, whether it be with jelly beans, jelly babies, or humbugs, at least until the HAPO study shows whether gestational diabetes is worth screening for. *Anne Dornhorst, Gary Frost Departments of *Metabolic Medicine and Nutrition and Dietetics, Imperial College School of Medicine at Hammersmith Hospital, London W12 ONN, UK 1
Jarrett RJ. Gestational diabetes: a non-entity? BMJ 1993; 306: 37–38. 2 Jarrett RJ, Castro-Soares J, Dornhorst A, Beard R. Should we screen for gestational diabetes? BMJ 1997; 315: 736–39. 3 Walkinshaw SA. Dietary regulation for gestational diabetes. In: Cochrane Library, Issue 4. Oxford: Update Software, 1999. 4 Walkinshaw SA. Very tight versus tight control for diabetes in pregnancy. In: Cochrane Library, Issue 1. Oxford: Update Software, 2000. 5 Naylor CD, Sermer M, Chen E, Sykora K, for the Toronto Trihospital Gestational Diabetes Investigators. Cesarean delivery in relation to birthweight and gestational glucose tolerance: pathophysiology or practice style? JAMA 1996; 275: 1165–70. 6 Hanson U, Persson B. Outcome of pregnancies complicated by type 1 insulin-dependent diabetes in Sweden: acute pregnancy complications, neonatal mortality and morbidity. Am J Perinatol 1993; 10: 330–33. 7 Silverman BL, Metzger BE, Cho NH, Leob CA. Impaired glucose tolerance in adolescents offspring of diabetic mothers. Diabetes Care 1995; 18: 611–17. 8 Pettitt DJ, Bennett PH, Knowler WC, Baird HR, Aleck KA. Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Long-term effects on obesity and glucose tolerance in the offspring. Diabetes 1985; 34 (suppl 2): 119–22. 9 http://www.hapo.nwu.edu (password required to access site). 10 Lamar ME, Kuehl TJ, Cooney AT, Gayle LJ, Holleman S, Allen SR. Jelly beans as an alternative to a fifty-gram glucose beverage for gestational diabetes screening. Am J Obstet Gynecol 1999; 181: 1154–57. 11 American Diabetes Association position statement: gestational diabetes. Diabetes Care 1999; 22 (suppl 1): S74–76.
Lancet peer reviewers Without expert external advisers, a peer-reviewed journal such as The Lancet would not be viable. Today we list on our website our 2700 or so helpers for 1999. This number is an increase on 1998, when we called on just over 2200 advisers for their opinion. Peer reviewers work for little reward—we provide a part-subscription for clinicians or scientists, or a small cash sum for our statistical advisers.With today’s listing go the thanks of the journal’s editors. David McNamee The Lancet, London WC1X 8RR, UK
THE LANCET • Vol 355 • February 26, 2000
documented episodes of cerebral malaria and each used a paired case-control design to look for cognitive impairments that could be associated with the previous illness. In the Gambian study,3 the proportion of children with a cognitive or sensorimotor disability did not differ between cases and controls. In a more recent study from Kenya,4 there were significantly more children with cognitive impairment among the cases (12/87) than among the controls (3/87). What is to be made of these discrepant findings? Both groups used a battery of tests of intellectual, sensorimotor, and behavioural functions that had been piloted locally and adapted to the local language and culture. The tests were given on two separate occasions in the home of each individual. Differences in the actual tests applied could have affected the results. Moreover, the children in the Gambian study were older (mean age 42 months) than those in the Kenyan study (mean age 26 months) at the time of the original episode of cerebral malaria. Another important difference between the studies is that the Gambian investigators included only children who had no detectable neurological sequelae at the end of their original illness. Among the 75 children in the Kenyan study without initial sequelae, five were cognitively impaired at the time of the follow-up assessment, compared with three of the 87 controls; five of 12 children with neurological sequelae at the end of their original illness had no detectable neurological or cognitive deficit a few years later. To know for certain the risk and extent of cognitive impairment in children who recover from cerebral malaria with no detectable neurological deficit, larger studies would be needed. These are difficult to achieve. The impressive studies described above required the long-term presence of research teams and close and continuing access to communities. Meanwhile, there are enough reasons to do all that is possible to prevent cerebral malaria and, when it occurs, to treat it promptly and effectively. The above studies, and others observing the gross neurological sequelae of cerebral malaria,5,6 have identified features of the original illness that are prognostic of later cerebral impairment; among these factors, depth of coma and repeated or prolonged seizures have emerged in almost all studies as being prognostically important. Do seizures of themselves contribute to brain damage, or merely reflect the severity of underlying abnormality? This question, with its important implications for the management of cerebral malaria, can be determined only by an intervention specifically directed against seizures. But what is an effective measure for prevention of seizures in children with cerebral malaria? In this issue of The Lancet, Jane Crawley and colleagues report a trial of one such measure in children with cerebral malaria admitted to a district hospital in Kilifi, Kenya. In a double-blind study, they randomly allocated 340 children phenobarbital 20 mg/kg or placebo by intramuscular injection, then treated all with appropriate antimalarial, antibiotic, and anticonvulsant drugs and supportive therapy. They recorded clinical developments, including seizures during the illness, and outcomes. An interim analysis, the results of which were not disclosed to the investigators, showed that children in the phenobarbital group had significantly fewer seizures and neurological sequelae than the placebo group; a trend of more deaths in the phenobarbital group did not reach statistical significance. Had the study been stopped accordingly at this point, phenobarbital 20 mg/kg may have been 672
recommended throughout Africa as being beneficial against convulsions in cerebral malaria, with potentially disastrous consequences. The monitors in this study correctly continued the study, which then showed a significantly higher mortality in the phenobarbital group than in the placebo group. Was the excess of deaths due to phenobarbital, or to the additional effect of three or more doses of diazepam in some of these patients? The study cannot provide an answer, since those children needing additional diazepam are likely to have had more severe disease, and may have been more susceptible to phenobarbital for that reason alone. Studies are still needed to guide the use of anticonvulsants in cerebral malaria. Whether smaller doses of phenobarbital, or alternative drug(s), are evaluated, numbers must be large enough to detect an effect on seizures and on mortality and sequelae. Numbers must be even larger if patients are to be followed over several years to detect benefit against subtle impairments that may persist in the long term. Malcolm E Molyneux Wellcome Trust Research Laboratories, College of Medicine, University of Malawi, Box 30096, Blantyre 3, Malawi; and School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, UK 1 2 3
4
5
6
Brewster DR, Kwiatkowski D,White NJ. Neurological sequelae of cerebral malaria in children. Lancet 1990; 336: 1039–43. Bondi FS.The incidence and outcome of neurological abnormalities in childhood cerebral malaria. Trans R Soc Trop Med Hyg 1992; 86: 17–19. Muntendam AH, Jaffar S, Bleichrodt N, van Hensbroek MB. Absence of neuropsychological sequelae following cerebral malaria in Gambian children. Trans R Soc Trop Med Hyg 1996; 90: 391–94. Holding PA, Stevenson J, Peshu N, Marsh K. Cognitive sequelae of severe malaria with impaired consciousness. Trans R Soc Trop Med Hyg 1999; 93: 529–34. Molyneux ME, Taylor TE,Wirima JJ, Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 1989; 71: 441–59. Van Hensbroek MB, Palmer A, Jaffar S, Schneider G, Kwiatkowski D. Residual neurological sequelae after childhood cerebral malaria. J Pediatr 1997; 131: 125–29.
Awareness of awareness during general anaesthesia See page 707 Io non mori’, e non rimasi vivo; Pensa omai per te, s’hai fior d’ingegno, Qual io divenni, d’uno e d’altro privo. [Neither did I die, nor did I remain alive; Imagine yourself, if your spirit is fine, what I came to be, deprived of both.] —Dante, Inferno XXXIV, 25–27.
Within the indeterminate state called anaesthesia, awareness can persist or re-emerge. Semantically a contradiction (unawareness is part of the definition of anaesthesia), logically a paradox, awareness during general anaesthesia is a pitfall for the anaesthetist, a horror for the patient, an invitation for the prosecutor. Since awareness during general anaesthesia came into being on the very days that inhalational anaesthetics were inaugurated—the first patients given nitrous oxide by Horace Wells in 1845 and ether by William TG Morton in 1846 were “half-awake” and reported feeling pain during surgery—the topic of Rolf Sandin and colleagues’ report of their large and thorough study in today’s Lancet is hardly novel. Wherein lies the interest in this paper?
THE LANCET • Vol 355 • February 26, 2000
COMMENTARY
In 1997 and 1998 Sandin and colleagues questioned almost all (97%) surgical patients aged over 15 years in two Swedish hospitals about explicit recall of intraoperative events (ie, awareness during anaesthesia). Together these patients had undergone a wide range of procedures, and nearly all had received inhalational anaesthetics (two-thirds of them sevoflurane, a third isoflurane). Sandin and colleagues found 18 cases of awareness among nearly 12 000 patients. How does this rate of 0·15% compare with previous reports? Measurements depend on what is measured and how it is measured. Sandin restricted his inquiry to explicit forms of memory—ie, conscious awareness with spontaneous recall of events. Dreaming and implicit memory (the recondite realm of unconscious perceptions, learning, and absorption of “advertising” messages during anaesthesia1) were not explored. Hypnotists can extract recollections of intraoperative events in a high proportion of patients (four out of ten patients in a famous case-series reported by Levinson2 who, however, could not repeat the feat 30 years later). Sandin and colleagues did not use hypnosis. Patients were interviewed on leaving the recovery room, 1–3 days later, and 1–2 weeks later. The first interview detected only half the cases of awareness eventually identified. Although other anaesthetists fear that “it is easy for patients to imagine more than they actually experienced if considerable time elapsed between the anaesthetic and the [interview]”,3 Sandin’s findings suggest that accurate explicit recall of intraoperative events may be delayed. The overall percentage of people reporting awareness in Sandin and colleagues’ paper is lower than that found in previous surveys in similar mixed surgical settings.4–6 The Swedish surgical cohort did not include cardiacsurgery patients (whose brains may be awake because they are sometimes anaesthetised such as to spare the heart) but it included trauma victims and patients who underwent caesarean sections (groups also classically semi-dormient, the former because anaesthetic agents, commonly cardiovascular depressants, may worsen shock, the latter so that strongly crying babies are extracted). The finding of only one case of awareness among the caesarean group may be because the women were put under adequate general anaesthesia7 or because most of them were delivered under spinal or epidural anaesthesia—ie, under a state of deliberate painless awareness. The curare-like drugs were introduced in the 1940s and 1950s and ever since the publication of the first reports of awake-paralysed patients (those who receive muscle relaxants together with inadequate amounts of anaesthetic drugs),8 it has generally been accepted that “spontaneous recall” during general anaesthesia is confined almost entirely to such patients.9 However, non-paralysed patients may be aware-awake too; in Sandin’s study patients not given muscle relaxants had a lower, albeit not zero, risk of awareness than did those given neuromuscular blocking agents (0·18% vs 0·10%). Delayed neurotic symptoms (post-traumatic stress disorder) can follow awareness during general anaesthesia.10 As recognised since the first reports of this complication after general anaesthesia 25 years ago, neurotic symptoms in the Swedish surgical patients who reported awareness during general anaesthesia were more likely among those who were paralysed than among those who were not paralysed by neuromuscular
THE LANCET • Vol 355 • February 26, 2000
blocking agents, and when the patient had experienced intense pain while under anaesthesia. A striking finding in Sandin’s study is the relation between delayed neurotic symptoms and the patient’s inability to understand what was actually happening during undesired wakefulness. This point raises the question of whether the possibility of awareness should be discussed with the patient preoperatively to reduce the likelihood of neurotic symptoms, or whether doing so would worry too many patients unnecessarily. With the anaesthetist’s explanations and reassurance, reiterated until the patient was satisfied, neuropsychiatric symptoms in all of the patients resolved within 3 weeks, without psychiatric support. Patients in other reports have been less lucky,9 perhaps because explanation and reassurance were not as timely. Since most cases of awareness are due to faulty apparatus of technique,11 prevention justifiably focuses on equipment and training. In addition, various monitoring devices have been proposed for assessment of the state of awareness, or the depth of anaesthesia, to find out whether a patient is not really asleep when he or she ought to be.3 Sandin and colleagues’ findings cast doubt on the belief that one of these methods —namely, monitoring of expiratory anaesthetic-gas concentration—helps avoid awareness. And they suggest caution before adopting novel neurophysiological monitoring techniques allegedly capable of reducing the likelihood of awareness. Assessment of the reliability of these methods would require huge clinical trials. When it comes to rare events, evidence-based anaesthesia is hard to achieve. Another accepted dogma challenged by Sandin and colleagues’ findings is that benzodiazepines do not afford protection from awareness, and they rightly question the use of these drugs to prevent patients from remembering awareness should it occur. That no case of awareness in Sandin’s study was due to equipment failure is a favourable reflection of anaesthetic practice at the two Swedish hospitals. Another commendable feature of practice there, which reflects concern for patients’ comfort, is that the anaesthetists routinely ask patients about awareness. Awareness may be accepted by anaesthetists as an inevitable occurrence, but it is not acceptable to the patient, even if he is himself an anaesthetist.12 Awareness of awareness is the first step out. Bruno Simini Ospedale, 55100 Lucca, Italy 1 Anonymous. Advertising during anaesthesia? Lancet 1986; ii: 1019–20. 2 Levinson BW. States of awareness during general anaesthesia. Br J Anaesth 1965; 37: 544–46. 3 Bailey AR, Jones JG. Patients’ memories of events during general anaesthesia. Anaesthesia 1997; 52: 460–76. 4 Liu WHD, Thorp TAS, Graham SG, Aitkenhead AR. Incidence of awareness with recall during general anaesthesia. Anaesthesia 1991; 46: 435–37. 5 Sandin R, Nordström O. Awareness during total iv anaesthesia. Br J Anaesth 1993; 71: 782–87. 6 Ranta SO-V, Laurila R, Saario J, Ali-Melkkilä T, Hynynen M. Awareness with recall during general anesthesia: incidence and risk factors. Anesth Analg 1998; 86: 1084–89. 7 Reynolds F. Anaesthesia for caesarean section: no need for nightmares. Anesthesia 1986; 41: 652. 8 Anonymous. Awareness during anaesthesia. Lancet 1973; ii: 1305. 9 Aitkenhead AR. Awareness during anaesthesia: when is an anaesthetic not an anaesthetic? Can J Anaesth 1996; 43: 206–11.
673
COMMENTARY 10 Schwender D, Kunze-Kronawitter H, Dietrich P, Klasing S, Forst H, Madler C. Perceptions, emotions, cognition and reactions. Br J Anaesth 1998; 80: 133–39. 11 Brighouse D, Norman J. To wake in fright. BMJ 1992; 304: 1327–28. 12 Peduto VA, Silvetti L, Piga M. [An anaesthetized anaesthetist tells his experience of waking up accidentally during an operation]. Minerva Anestesiol 1994; 60: 1–5.
Jelly-beans, only a colourful distraction from gestational glucose-challenge tests In 1993 John Jarrett questioned the very existence of gestational diabetes,1 and today the debate on whether pregnant women should be screened for glucose intolerance continues.2 Those against universal screening point to the lack of randomised controlled studies showing any tangible benefit in terms of perinatal mortality and morbidity derived from screening for or treatment of glucose intolerance.3,4 Meanwhile the screening process itself, they argue, creates an obstetric environment that promotes unnecessary operative deliveries for women whose only risk factor is asymptomatic hyperglycaemia.5 The opponents of screening are commonly epidemiologists and publichealth physicians who live their life according to the credo of evidence-based medicine, and as a group are rarely left holding the macrosomic baby or dealing with a difficult shoulder delivery. Those in favour are more likely to be obstetric physicians with a wealth of anecdotal experience of dealing with the emotional aftermath of stillbirth and birth trauma, which, rightly or wrongly, have been attributed to gestational diabetes. For these obstetricians, not to screen is tantamount to negligence. They highlight the point that the higher the maternal blood-glucose concentrations in women with pre-gestational diabetes, the stronger the association with perinatal mortality and morbidity, childhood obesity, and diabetes in early adult life.6–8 With a certain leap of faith they extrapolate downwards to lesser degrees of glucose intolerance, to conclude that there is a continuum of risk between maternal blood-glucose concentrations and adverse pregnancy outcome that extends into the normal glycaemic range. So what next? The answer has to be to sit back, be patient, and wait until 2003, when the results of the HAPO (Hyperglycaemia Adverse Pregnancy Outcome) Study, funded by the US National Institutes of Health, become available.9 This study will involve 16 centres, three continents, and 25 000 unselected pregnant women who will undergo a 75 g oral glucose-tolerance test at 28 weeks of pregnancy. Only women who fulfil the WHO criteria for diabetes will be treated, so all lesser degrees of hyperglycaemia can be correlated with shortterm variables of pregnancy outcome. Follow-up studies will allow the examination of the medium-term and long-term effects of maternal hyperglycaemia on the future health of the mother and her child. Only after this study will the threshold of maternal blood-glucose concentration that carries no added risk to pregnancy be known. Until then no effort should be made to rewrite and redefine the screening and diagnostic criteria for gestational diabetes. It is against this background that one needs to consider the recent paper by Michael Lamar and colleagues10 on the use of jelly beans for screening for gestational diabetes. Lamar and colleagues purport that a fistful of 28 jelly beans (nine colours and ten flavours) 674
is a more mother-friendly screening test for gestational diabetes than the usual 50 g oral glucose drink, because it causes less nausea, headache, and sweating. They compared the 1 h serum glucose value after a 50 g oral glucose drink with that after a 50 g glucose load as found in 28 jelly beans. 136 women, who were 24–28 weeks pregnant, participated in both screening tests, and all subsequently underwent a diagnostic 3 h oral glucose-tolerance test.11 Of the 136 women five had gestational diabetes; two of these had screened positive with the jelly-bean test and four with the glucose drink, giving sensitivity values for these screening tests of 40% and 80%, respectively. The positive predictive values of these two tests would be expected to become even more discrepant among populations with higher prevalence rates of gestational diabetes. Hence the jelly-bean jar should remain firmly shut, and any temptation to develop confectionery screening should be discouraged, whether it be with jelly beans, jelly babies, or humbugs, at least until the HAPO study shows whether gestational diabetes is worth screening for. *Anne Dornhorst, Gary Frost Departments of *Metabolic Medicine and Nutrition and Dietetics, Imperial College School of Medicine at Hammersmith Hospital, London W12 ONN, UK 1
Jarrett RJ. Gestational diabetes: a non-entity? BMJ 1993; 306: 37–38. 2 Jarrett RJ, Castro-Soares J, Dornhorst A, Beard R. Should we screen for gestational diabetes? BMJ 1997; 315: 736–39. 3 Walkinshaw SA. Dietary regulation for gestational diabetes. In: Cochrane Library, Issue 4. Oxford: Update Software, 1999. 4 Walkinshaw SA. Very tight versus tight control for diabetes in pregnancy. In: Cochrane Library, Issue 1. Oxford: Update Software, 2000. 5 Naylor CD, Sermer M, Chen E, Sykora K, for the Toronto Trihospital Gestational Diabetes Investigators. Cesarean delivery in relation to birthweight and gestational glucose tolerance: pathophysiology or practice style? JAMA 1996; 275: 1165–70. 6 Hanson U, Persson B. Outcome of pregnancies complicated by type 1 insulin-dependent diabetes in Sweden: acute pregnancy complications, neonatal mortality and morbidity. Am J Perinatol 1993; 10: 330–33. 7 Silverman BL, Metzger BE, Cho NH, Leob CA. Impaired glucose tolerance in adolescents offspring of diabetic mothers. Diabetes Care 1995; 18: 611–17. 8 Pettitt DJ, Bennett PH, Knowler WC, Baird HR, Aleck KA. Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Long-term effects on obesity and glucose tolerance in the offspring. Diabetes 1985; 34 (suppl 2): 119–22. 9 http://www.hapo.nwu.edu (password required to access site). 10 Lamar ME, Kuehl TJ, Cooney AT, Gayle LJ, Holleman S, Allen SR. Jelly beans as an alternative to a fifty-gram glucose beverage for gestational diabetes screening. Am J Obstet Gynecol 1999; 181: 1154–57. 11 American Diabetes Association position statement: gestational diabetes. Diabetes Care 1999; 22 (suppl 1): S74–76.
Lancet peer reviewers Without expert external advisers, a peer-reviewed journal such as The Lancet would not be viable. Today we list on our website our 2700 or so helpers for 1999. This number is an increase on 1998, when we called on just over 2200 advisers for their opinion. Peer reviewers work for little reward—we provide a part-subscription for clinicians or scientists, or a small cash sum for our statistical advisers.With today’s listing go the thanks of the journal’s editors. David McNamee The Lancet, London WC1X 8RR, UK
THE LANCET • Vol 355 • February 26, 2000