- Email: [email protected]
Awareness during anaesthesia
CORRESPONDENCE
COMMENTARY
CORRESPONDENCE
Awareness during anaesthesia Sir—We are concerned by the contention held by Rolf Sandin and colleagues (Feb 26, p 707)1 that “The extent [to which] end tidal anaesthetic gas concentration (ETAGC) monitoring reduces the incidence of awareness is seriously questionable”. Although their study showed that ETAGC monitors did not have an impact on the incidence of awareness during anaesthesia, it does not necessarily follow that using ETAGC monitors appropriately would not reduce this complication. It was not stated in the article whether alarms were set to alert the clinician when the ETAGC fell below a particular level. Also, it was not clear what the ETAGC was at the point of awareness in patients with an identifiable awareness episode. There are compelling arguments to suggest that ETAGC is the most reliable indicator of sufficient depth of anaesthesia. There is a narrow intersubject variability in response to potent volatile anaesthetic agents,2 so the ETAGC can usually be used to predict whether the patient is likely to be adequately anaesthetised. In contrast, drugs like opioids have unpredictable pharmacodynamic responses.3 Intravenous anaesthetic agents like propofol and remifentanil are administered according to general pharmacodynamic models, which might not always be applicable to individual patients. Blood concentrations of intravenous anaesthetic agents are not routinely measured, thus an error in the delivery of these agents might not be detected.4 Of course the most reliable monitor of awareness would be a device which focused on the brain. Although such devices are available, there are inherent difficulties in validating such equipment because awareness under anaesthesia is rare.1 For now, we must rely on our knowledge, clinical acumen, and surrogate markers. The pulse oximeter is a surrogate marker for tissue hypoxia. It has not been
THE LANCET • Vol 355 • May 13, 2000
shown to decrease mortality, but it is safe, reliable, non-invasive, and there is good rationale for its routine use during anaesthesia. ETAGC monitors are also safe, reliable, non-invasive, and provide potentially useful information. There is every reason that they too should form part of the standard care of the anaesthetised patient. *Paul Downie, Michael Avidan Department of Anaesthetics, King’s College Hospital, London SE5, UK (e-mail: paul@theharp. globalnet.co.uk) 1
2
3
4
Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet 2000; 355: 707–11. Rehberg B, Bouillon T, Zinserling J, Hoeft A. Comparative pharmacodynamic modelling of the electroenecephalographyslowing effect of isoflurane, sevoflurane, and desfulrane. Anesthesiology 1999; 91: 397–405. Jenstrup M, Fruegard K, Nielsen J, Moller AM, Wilberg-Jorgensen F. Alfentanil infusion in total intravenous anaesthesia (TIVA). Population pharmacokinetics fails to predict plasma concentrations of alfentanil. Acta Anaesthesiol Scand 1992; 36: 846–47. Tong D, Chung F. Recall after total intravenous anaesthesia due to an equipment misuse. Can J Anasth 1997; 44: 73–74.
Sir—Rolf Sandin and co-workers1 found a low incidence of 0·2% for intraoperative awareness. They are to be congratulated for the repeated interview technique in their study design, although they only tested explicit memory. However, there are several points that need some comment. The investigators stated that there are no studies showing important background information for the conditions on which intraoperative awareness is most likely to occur. Among others Domino and colleagues2 described an analysis of the malpractice database from the American Society of Anesthesiologists Closed Claims Project, from which 1·9% of the claims were found to be associated with awareness. By logistic regression
analysis they showed that the risk factors for intraoperative awareness in these claims were: women younger than 60 years and intraoperative use of muscle relaxants.2 The results reported by Sandin and colleagues (12 of 19 patients were women and two were older than 60 years) confirm the findings of Domino and colleagues, but in a prospective manner. Sandin and colleagues stated that the study challenges the accepted dogma of benzodiazepines protecting from awareness. However, the investigators do not specifically describe which benzodiazepines, at what time, and at what dose their patients received these drugs. Despite the difference in amnesic action for single compounds, benzodiazepines are superior to other intravenous anaesthetic agents in producing amnesia.3 Contrary to common clinical understanding, N2O does not prevent recall, nor does it augment depth of anaesthesia. High doses of volatile anaesthetics might not exclude awareness per se, as assumed by Sandin and colleagues. Minimum alveolar concentration (MAC) of a volatile anaesthetic represents the anaesthetic concentration by which 50% of the patients will not move at skin incision. However, it has been shown by Rampil and others,4 that the MAC is no different in animals that have been decerebrated, so MAC does not cover depth of anaesthesia at all. If we believe that the incidence of intraoperative awareness in nonobstetric and non-cardiac cases is about 0·2% there will be between 23 000–40 000 new cases of awareness during anaesthesia each year in the USA alone (20 million general anaesthetics per year; incidence of 1:500 or 1:861). Such awareness is rare, but it will still result in major consequences for the patients involved.5 New monitoring tools, such as the Bispectral (BIS)-index analysis or middle latency auditory evoked responses monitor are now available. If
1721
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE
we fail to predict which state of unconsciousness is accomplished, these devices may help us to assess the degree of hypnosis attained, or they might alert us, for instance if a predetermined level of hypnosis is not reached as a result of technical failure, such as vapour failure. Whether these neuromonitoring tools prevent intraoperative episodes of recall, remains to be established by large-scale prospective clinical studies. One of the least expensive methods of minimising recall might be to put headsets on patients throughout anaesthesia so music can be played to them. *Hartmut Buerkle, Rainer Wuesten Klinik und Poliklinik für Anästhesiologie und operative intensivmedizin, Westfälische Wilhelms-Uiversität Münster, Munster D-48149, Germany 1
2
3
4
5
Sandin R, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet 2000; 355: 707–11. Domino KB, Posner KL, Caplan RA, Cheney FW. Awareness during anaesthesia: a closed claims analysis. Anesthesiology 1999; 90: 1053–61. Crawford ME, Carl P, Andersen RS, Mikkelsen BO. Comparison between midazolam and thiopentone-based balanced anaesthesia for day-case surgery. Br J Anaesth 1984; 56: 165–69. Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 1993; 78: 707–12. Osterman JE, van der Kolk BA. Awareness during anesthesia and posttraumatic stress disorder. Gen Hosp Psychiatry 1998; 20: 274–81.
Sir—Sandin and his colleagues1 make a substantial contribution to the published work on awareness during anaesthesia, but their paper has one important omission. The investigators do not describe what clinical signs the anaesthetists used to detect this potential complication. Since a muscle relaxant is almost certain to completely prevent even the slightest motor response to a stimulus, such as tracheal intubation or surgery, it is essential to ensure the patient is fully unconscious before its administration. I nip the patient’s ear to test for a response, such as a frown or a slight limb movement. Any slight response is an indication for more induction agent to be administered. The signs of inadequate anaesthesia during surgery are well recognised,2 and include, for example, unexpected hypertension and tachycardia as a result of increased sympathetic activity, lacrimation, and if the patient is not paralysed, other facial signs, such as frowning, or other motor activity. Any future study
1722
of awareness during anaesthesia should include a record of all such clinical signs. Alan Gilston 20 Hocroft Avenue, London NW2 2EH, UK. 1
2
Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective study. Lancet 2000; 355: 707–11. Heier T, Steen PA. Awareness in anaesthesia: incidence, consequences and prevention. Acta Anaesthesiol Scand 1996; 40: 1073–86.
Authors’ reply Sir—Paul Downie and Michael Avidan question whether ETAGC was properly used in the patients with awareness. Perhaps not, but even if too low an ETAGC was accepted by the anaesthetists in these patients, we studied real world anaesthesia, which may occasionally be substandard. However, this is what the average patient will experience, and that is what determines whether we need better education, BIS, or any other measure to be introduced. Except for the five cases of wakefulness during laryngoscopy that occurred before any inhalation agent had been administered, it was not possible to discover with accuracy when, or what concentration of anaesthetic was insufficient. Downie and Avidan put forward all the theoretical shortcomings of intravenous anaesthesia that makes it so important to seriously question why measurement of ETAGC in inhalational anaesthesia still fails to provide protection against awareness.2 We speculate that awareness in anaesthesia is, for several reasons, not often a result of factors that can be avoided by ETAGC monitoring. We highlighted the fact that awareness occurred during laryngoscopy in at least five of 14 intubated patients, a situation in which ETAGC is of no value. However, we believe that the use of ETAGC should continue, but that there should be far more realistic expectations of such monitoring. To us, “important background information” means something that may be subjected to change, and hence, expected to alter the incidence of awareness, such as the implementation of ETAGC, BIS, or the use of benzodiazepines, not sex or age, as suggested by Hartmut Buerkle and Rainer Wuesten. Even if high-risk populations should be identified, we cannot do very much to reduce the incidence of awareness unless we refuse to anaesthetise these patients. Nevertheless, the remark by Buerkle and Wuesten touches on a far more important issue—scientific evidence. A
closed-claims database may be biased in several ways, a fact that Domino and colleagues acknowledged in their paper.3 Three other studies in which patients with awareness have been recruited by advertising or retrospective referral are also subject to bias. Buerkle and Wuesten claim that we found an over representation of female sex among the cases of awareness in our paper; in fact we found no difference in the incidence of awareness between men and women,2 and their misinterpretation strengthens the argument for the need for sufficiently large prospective studies to be done. We do not understand the discussion on benzodiazepines by Buerkle and Wuesten. However, the patients who received benzodiazepines had been given standard premedication doses at the discretion of the individual anaesthetist, 1·25–3·75 mg midazolam, intravenously, or diazepam 5–15 mg orally. This did not offer protection against explicit recall. The suggestion that “high doses of volatile anaesthetics might not exclude awareness”, is a surprising opinion, to our knowledge completely unsupported, and it is certainly not based on the results by Rampil and colleagues, as stated. The subcortical motor response to noxious stimulation is definitely not equal to consciousness. With all due respect, and an assumption that the proposed methods work well for Alan Gilstone, to our knowledge, all scientific studies concerning vital signs, alone or in combinations, have invariably shown the same result. The vital signs are not reliable indicators of awareness.4 We have assessed our data, but abstained from writing yet another paper on the inability to identify awareness by haemodynamic variables. *R H Sandin, C Lennmarken, G Enlund, P Samuelsson Department of Anaesthesia and Intensive Care, Länssjukhuset, S-391 85 Kalmar, Sweden (e-mail: [email protected]) 1
2
3
4
Nordström O, Engström AM, Persson S, Sandin R. Incidence of awareness in total i.v. anaesthesia based on propofol, alfentanil and neuromuscular blockade. Acta Anaesthesiol Scand 1997; 41: 978–84. Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during general anaesthesia: a prospective case study. Lancet 2000; 355: 707–11. Domino KB, Posner KL, Caplan RA, Cheney FW. Awareness during anaesthesia: a closed claims analysis. Anesthesiology 1999; 90: 1053–61. Ghoneim MM, Block RI. Learning and memory during general anesthesia: an update. Anesthesiology 1997; 87: 387–410.
THE LANCET • Vol 355 • May 13, 2000
COMMENTARY
CORRESPONDENCE
Awareness during anaesthesia Sir—We are concerned by the contention held by Rolf Sandin and colleagues (Feb 26, p 707)1 that “The extent [to which] end tidal anaesthetic gas concentration (ETAGC) monitoring reduces the incidence of awareness is seriously questionable”. Although their study showed that ETAGC monitors did not have an impact on the incidence of awareness during anaesthesia, it does not necessarily follow that using ETAGC monitors appropriately would not reduce this complication. It was not stated in the article whether alarms were set to alert the clinician when the ETAGC fell below a particular level. Also, it was not clear what the ETAGC was at the point of awareness in patients with an identifiable awareness episode. There are compelling arguments to suggest that ETAGC is the most reliable indicator of sufficient depth of anaesthesia. There is a narrow intersubject variability in response to potent volatile anaesthetic agents,2 so the ETAGC can usually be used to predict whether the patient is likely to be adequately anaesthetised. In contrast, drugs like opioids have unpredictable pharmacodynamic responses.3 Intravenous anaesthetic agents like propofol and remifentanil are administered according to general pharmacodynamic models, which might not always be applicable to individual patients. Blood concentrations of intravenous anaesthetic agents are not routinely measured, thus an error in the delivery of these agents might not be detected.4 Of course the most reliable monitor of awareness would be a device which focused on the brain. Although such devices are available, there are inherent difficulties in validating such equipment because awareness under anaesthesia is rare.1 For now, we must rely on our knowledge, clinical acumen, and surrogate markers. The pulse oximeter is a surrogate marker for tissue hypoxia. It has not been
THE LANCET • Vol 355 • May 13, 2000
shown to decrease mortality, but it is safe, reliable, non-invasive, and there is good rationale for its routine use during anaesthesia. ETAGC monitors are also safe, reliable, non-invasive, and provide potentially useful information. There is every reason that they too should form part of the standard care of the anaesthetised patient. *Paul Downie, Michael Avidan Department of Anaesthetics, King’s College Hospital, London SE5, UK (e-mail: paul@theharp. globalnet.co.uk) 1
2
3
4
Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet 2000; 355: 707–11. Rehberg B, Bouillon T, Zinserling J, Hoeft A. Comparative pharmacodynamic modelling of the electroenecephalographyslowing effect of isoflurane, sevoflurane, and desfulrane. Anesthesiology 1999; 91: 397–405. Jenstrup M, Fruegard K, Nielsen J, Moller AM, Wilberg-Jorgensen F. Alfentanil infusion in total intravenous anaesthesia (TIVA). Population pharmacokinetics fails to predict plasma concentrations of alfentanil. Acta Anaesthesiol Scand 1992; 36: 846–47. Tong D, Chung F. Recall after total intravenous anaesthesia due to an equipment misuse. Can J Anasth 1997; 44: 73–74.
Sir—Rolf Sandin and co-workers1 found a low incidence of 0·2% for intraoperative awareness. They are to be congratulated for the repeated interview technique in their study design, although they only tested explicit memory. However, there are several points that need some comment. The investigators stated that there are no studies showing important background information for the conditions on which intraoperative awareness is most likely to occur. Among others Domino and colleagues2 described an analysis of the malpractice database from the American Society of Anesthesiologists Closed Claims Project, from which 1·9% of the claims were found to be associated with awareness. By logistic regression
analysis they showed that the risk factors for intraoperative awareness in these claims were: women younger than 60 years and intraoperative use of muscle relaxants.2 The results reported by Sandin and colleagues (12 of 19 patients were women and two were older than 60 years) confirm the findings of Domino and colleagues, but in a prospective manner. Sandin and colleagues stated that the study challenges the accepted dogma of benzodiazepines protecting from awareness. However, the investigators do not specifically describe which benzodiazepines, at what time, and at what dose their patients received these drugs. Despite the difference in amnesic action for single compounds, benzodiazepines are superior to other intravenous anaesthetic agents in producing amnesia.3 Contrary to common clinical understanding, N2O does not prevent recall, nor does it augment depth of anaesthesia. High doses of volatile anaesthetics might not exclude awareness per se, as assumed by Sandin and colleagues. Minimum alveolar concentration (MAC) of a volatile anaesthetic represents the anaesthetic concentration by which 50% of the patients will not move at skin incision. However, it has been shown by Rampil and others,4 that the MAC is no different in animals that have been decerebrated, so MAC does not cover depth of anaesthesia at all. If we believe that the incidence of intraoperative awareness in nonobstetric and non-cardiac cases is about 0·2% there will be between 23 000–40 000 new cases of awareness during anaesthesia each year in the USA alone (20 million general anaesthetics per year; incidence of 1:500 or 1:861). Such awareness is rare, but it will still result in major consequences for the patients involved.5 New monitoring tools, such as the Bispectral (BIS)-index analysis or middle latency auditory evoked responses monitor are now available. If
1721
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE
we fail to predict which state of unconsciousness is accomplished, these devices may help us to assess the degree of hypnosis attained, or they might alert us, for instance if a predetermined level of hypnosis is not reached as a result of technical failure, such as vapour failure. Whether these neuromonitoring tools prevent intraoperative episodes of recall, remains to be established by large-scale prospective clinical studies. One of the least expensive methods of minimising recall might be to put headsets on patients throughout anaesthesia so music can be played to them. *Hartmut Buerkle, Rainer Wuesten Klinik und Poliklinik für Anästhesiologie und operative intensivmedizin, Westfälische Wilhelms-Uiversität Münster, Munster D-48149, Germany 1
2
3
4
5
Sandin R, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet 2000; 355: 707–11. Domino KB, Posner KL, Caplan RA, Cheney FW. Awareness during anaesthesia: a closed claims analysis. Anesthesiology 1999; 90: 1053–61. Crawford ME, Carl P, Andersen RS, Mikkelsen BO. Comparison between midazolam and thiopentone-based balanced anaesthesia for day-case surgery. Br J Anaesth 1984; 56: 165–69. Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 1993; 78: 707–12. Osterman JE, van der Kolk BA. Awareness during anesthesia and posttraumatic stress disorder. Gen Hosp Psychiatry 1998; 20: 274–81.
Sir—Sandin and his colleagues1 make a substantial contribution to the published work on awareness during anaesthesia, but their paper has one important omission. The investigators do not describe what clinical signs the anaesthetists used to detect this potential complication. Since a muscle relaxant is almost certain to completely prevent even the slightest motor response to a stimulus, such as tracheal intubation or surgery, it is essential to ensure the patient is fully unconscious before its administration. I nip the patient’s ear to test for a response, such as a frown or a slight limb movement. Any slight response is an indication for more induction agent to be administered. The signs of inadequate anaesthesia during surgery are well recognised,2 and include, for example, unexpected hypertension and tachycardia as a result of increased sympathetic activity, lacrimation, and if the patient is not paralysed, other facial signs, such as frowning, or other motor activity. Any future study
1722
of awareness during anaesthesia should include a record of all such clinical signs. Alan Gilston 20 Hocroft Avenue, London NW2 2EH, UK. 1
2
Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective study. Lancet 2000; 355: 707–11. Heier T, Steen PA. Awareness in anaesthesia: incidence, consequences and prevention. Acta Anaesthesiol Scand 1996; 40: 1073–86.
Authors’ reply Sir—Paul Downie and Michael Avidan question whether ETAGC was properly used in the patients with awareness. Perhaps not, but even if too low an ETAGC was accepted by the anaesthetists in these patients, we studied real world anaesthesia, which may occasionally be substandard. However, this is what the average patient will experience, and that is what determines whether we need better education, BIS, or any other measure to be introduced. Except for the five cases of wakefulness during laryngoscopy that occurred before any inhalation agent had been administered, it was not possible to discover with accuracy when, or what concentration of anaesthetic was insufficient. Downie and Avidan put forward all the theoretical shortcomings of intravenous anaesthesia that makes it so important to seriously question why measurement of ETAGC in inhalational anaesthesia still fails to provide protection against awareness.2 We speculate that awareness in anaesthesia is, for several reasons, not often a result of factors that can be avoided by ETAGC monitoring. We highlighted the fact that awareness occurred during laryngoscopy in at least five of 14 intubated patients, a situation in which ETAGC is of no value. However, we believe that the use of ETAGC should continue, but that there should be far more realistic expectations of such monitoring. To us, “important background information” means something that may be subjected to change, and hence, expected to alter the incidence of awareness, such as the implementation of ETAGC, BIS, or the use of benzodiazepines, not sex or age, as suggested by Hartmut Buerkle and Rainer Wuesten. Even if high-risk populations should be identified, we cannot do very much to reduce the incidence of awareness unless we refuse to anaesthetise these patients. Nevertheless, the remark by Buerkle and Wuesten touches on a far more important issue—scientific evidence. A
closed-claims database may be biased in several ways, a fact that Domino and colleagues acknowledged in their paper.3 Three other studies in which patients with awareness have been recruited by advertising or retrospective referral are also subject to bias. Buerkle and Wuesten claim that we found an over representation of female sex among the cases of awareness in our paper; in fact we found no difference in the incidence of awareness between men and women,2 and their misinterpretation strengthens the argument for the need for sufficiently large prospective studies to be done. We do not understand the discussion on benzodiazepines by Buerkle and Wuesten. However, the patients who received benzodiazepines had been given standard premedication doses at the discretion of the individual anaesthetist, 1·25–3·75 mg midazolam, intravenously, or diazepam 5–15 mg orally. This did not offer protection against explicit recall. The suggestion that “high doses of volatile anaesthetics might not exclude awareness”, is a surprising opinion, to our knowledge completely unsupported, and it is certainly not based on the results by Rampil and colleagues, as stated. The subcortical motor response to noxious stimulation is definitely not equal to consciousness. With all due respect, and an assumption that the proposed methods work well for Alan Gilstone, to our knowledge, all scientific studies concerning vital signs, alone or in combinations, have invariably shown the same result. The vital signs are not reliable indicators of awareness.4 We have assessed our data, but abstained from writing yet another paper on the inability to identify awareness by haemodynamic variables. *R H Sandin, C Lennmarken, G Enlund, P Samuelsson Department of Anaesthesia and Intensive Care, Länssjukhuset, S-391 85 Kalmar, Sweden (e-mail: [email protected]) 1
2
3
4
Nordström O, Engström AM, Persson S, Sandin R. Incidence of awareness in total i.v. anaesthesia based on propofol, alfentanil and neuromuscular blockade. Acta Anaesthesiol Scand 1997; 41: 978–84. Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during general anaesthesia: a prospective case study. Lancet 2000; 355: 707–11. Domino KB, Posner KL, Caplan RA, Cheney FW. Awareness during anaesthesia: a closed claims analysis. Anesthesiology 1999; 90: 1053–61. Ghoneim MM, Block RI. Learning and memory during general anesthesia: an update. Anesthesiology 1997; 87: 387–410.
THE LANCET • Vol 355 • May 13, 2000