- Email: [email protected]
DOUBLE BURST STIMULATION (DBS): A NEW PATTERN OF NERVE STIMULATION TO IDENTIFY RESIDUAL NEUROMUSCULAR BLOCK
Br. J. Anaesth. (1989), 62, 274-278
DOUBLE BURST STIMULATION (DBS): A NEW PATTERN OF NERVE STIMULATION TO IDENTIFY RESIDUAL NEUROMUSCULAR BLOCK J. ENGB^EK, D. 0STERGAARD AND J. VIBY-MOGENSEN
SUMMARY We present a new pattern of nerve stimulation— double burst stimulation (DBS)—to detect residua/ neuromuscular block manually. The DBS consists of two short lasting, 50-Hz tetanic stimuli or bursts separated by a 750-ms interval. The response to this pattern of stimulation is two single separated muscle contractions of which the second is less than the first during nondepolarizing neuromuscular blockade. The ability to identify fade manually at different train-offour (TOF) ratios was compared in four DBS patterns in which different numbers of impulses in the individual bursts were combined. The DBS with three impulses in each burst (DBS3i3) was considered to be the most sensitive and the least painful and thus most suitable for clinical use. The degree of fade in TOF and DBS33 was almost identical at any level of blockade (correlation coefficient 0.96), and the major post-DBS 33 effect was a depression of the first twitch in TOF lasting less than 15 s. It is concluded that the DBS is more sensitive than the TOF in manual detection of residual block.
MATERIAL AND METHODS
Principle of double burst stimulation
Double burst stimulation consists of two short tetanic stimulations (bursts) separated by a short interval (fig. 1). If the frequency of the tetanic stimulation is not too low (i.e. ^ 30-40 Hz) and if the interval between the two bursts is not too short, the response to this stimulation pattern is two single separate muscle contractions. During JENS ENGBAK, M.D.; DORIS OSTERGAARD, M.D.; JBRGEN VIBY-
MOGENSEN, M.D., PH.D. ; Department of Anaesthesia, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. Accepted for Publication: July 5, 1988.
non-depolarizing neuromuscular block the response to the second burst of stimulation is less than that to the first, corresponding with fade to the TOF response (fig. 2). We postulated that any difference in the two responses in DBS was felt more easily than the difference between the first and the fourth response to TOF nerve stimulation. Different patterns of DBS can be designed from different combinations of three variables in the stimulation pattern: the frequency of tetanic stimulation, the duration of tetanic stimulation,
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
The. degree of residual neuromuscular block during recovery from non-depolarizing muscle relaxant drugs is evaluated normally from the response to train-of-four (TOF) nerve stimulation [1,2]. However, without quantitative recording of the evoked response it is difficult to estimate the TOF ratio. Thus when the TOF ratio has recovered to more than 0.4—0.5, fade in the response cannot be identified manually with sufficient accuracy to exclude residual curarization [3]. One reason for this may be that the two middle responses to TOF stimulation confound the estimation of the last response in relation to the first. Therefore, we postulated that a pattern of stimulation resulting in only two muscle contractions, but stressing the neuromuscular junction to the same extent as TOF stimulation, might improve the ability to identify fade manually. The purpose of this study was to evaluate if the use of two short lasting tetanic stimuli separated by a short interval—double burst stimulation (DBS)—can be used to diagnose residual neuromuscular block manually.
275
DOUBLE BURST STIMULATION
UUI
TABLE I. Different combinations of frequency and number of impulses in the first and the second burst of the DBS used in the pilot study. The interval between the bursts was 750 ms. DBS33, DBSi 4) DBS31, and DBSi3 are indicated. See text for further explanation Tetanic frequency
No. of impulses
20 ms DBS
750 ms
and the interval separating the two tetanic stimulations. However, the number of possible combinations of these variables is restricted and the frequency of the tetanic stimulation must exceed 30-40 Hz so that the muscle response to the stimuli in the burst fuses. On the other hand, to minimize the pain caused by stimulation, a frequency as low as possible should be chosen. The duration of the bursts also has to be short (two-to-four impulses) so that the muscle response is felt as a single short lasting contraction and not as a sustained response. The duration of the muscle contraction following such bursts is approximately 400-500 ms. Therefore, to have the two muscle responses clearly separated in the DBS, the interval between the individual bursts should be longer than the 500 ms separating the impulses in the TOF. Preliminary studies
In preliminary studies, nine different patterns of DBS were investigated (table I). On the basis of how easily fade was detected manually at different levels of block, a limited number of combinations of the variables were selected for further clinical 10s
FIG. 2. Mechanical twitch recording of a DBS 3 3 (at arrow). Notice that the degree of fade in the DBS response corresponds to the degree of fade in the TOF response.
DBS 3 , DBS 44 DBS 32 DBS 4 3
Burst 2
Burst 1
Burst 2
100 100 100 50 50 50 50 50 50
100 50 50 50 50 50 50 50 100
2 3 3 2 3 4 3 4 3
2 3 2 2 3 4 2 3 2
study. It was found that the major determinant of the response to DBS was the duration of the tetanic stimulation—that is, the number of impulses and not the frequency (50 or 100 Hz) used in the bursts. Further, if identical frequencies but different durations were used, a more pronounced difference between the two responses to DBS was felt. To have the muscle contractions separated as clearly as in the TOF response, an interval of 750 ms was selected in all DBS patterns used. Based on the results of these preliminary studies, four different patterns of DBS were selected for further clinical evaluation (table I). All the DBS patterns selected included the use of a 50-Hz tetanic stimulation. In DBS3 3 and DBS4 4, three and four impulses, respectively, were given in each tetanic burst. In DBS3 2 three impulses were given in the first burst and only two in the last; in DBS4 3 there were four and three impulses, respectively. Design of the main study
We studied 41 adult patients (ASA physical status I or II) undergoing elective gynaecological or gastroenterological surgery. None of the patients suffered from neuromuscular disease or received any drug that might alter neuromuscular function. The study was approved by the local Ethics Committee, but informed consent was not obtained as the anaesthetic and monitoring procedures were those used in standard practice. One hour after administration of diazepam 0.2 mg kg"1 by mouth, anaesthesia was induced with thiopentone 3-5 mg kg"1 i.v. and maintained
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
FIG. 1. Stimulation pattern in double burst stimulation (DBS). The time constants given are those of a DBS3 3. In each burst three impulses are given at a frequency of 50 Hz (one impulse every 20 ms). The two bursts are separated by 750 ms. See text for further explanation.
Burst 1
276
BRITISH JOURNAL OF ANAESTHESIA Part 3. Decurarizing effect of Z>BS33. The purpose of this study was to investigate a possible decurarizing effect of DBS stimulation. In seven patients, both the height of the first response in the TOF and the TOF ratio obtained from mechanical twitch recordings 3, 15 and 27 s after DBS3 3 were compared with the twitch height and the TOF ratio of the last TOF response preceding the DBS 3 3 during spontaneous recovery of the block. TOF and DBS stimulation were given as described in part 2. For statistical evaluation, Fisher's exact probability test, Chi-square test for two independent samples, Wilcoxon matched pairs signed ranks test, Student's t test and analyses of linear regression (least square methods) were used.
Part 1. Manual evaluation of DBS. The purpose of this part of the study was to investigate the four DBS patterns chosen from the pilot study in order to select the DBS with the highest sensitivity. In 24 patients the mechanical twitch was measured from one arm (the control arm) during TOF stimulation. On the other arm (the test arm) TOF stimulation was given as the basic pattern of stimulation. At regular intervals (more than every 2 min) a DBS stimulation was given in place of TOF stimulation. The four DBS (DBS 33 , DBS 44 , DBS3 2, and DBS4 3) were given in random order during spontaneous recovery of the block. The response to the selected DBS was evaluated manually by two observers without access to the TOF ratio measured in the control arm. The observers had to decide if fade was present in the DBS response.
RESULTS
Part 1 Table II shows the number of instances in which fade was felt in the four different DBS responses at different TOF ratios. The results obtained with DBS3>3 in the preliminary study and in part 1 were not statistically different and therefore were pooled. Thus the response to DBS3>3, DBS 44 , DBS 32 , and DBS 4 3 were evaluated 199, 129, 128 and 123 times, respectively. There was no statistically significant difference between DBS 3 3 and DBS 44 at any TOF ratio. Significantly more examples of fade were identified with DBS3 2 compared with DBS 3 3 when the TOF ratio was above 0.5. In the interval 0.81-0.90, a statistically significant difference was found also between DBS3 3 and DBS4 3. Generally, with any of the DBS selected, only few cases of fade were not felt when TOF ratio was Part 2. Relation between TOF ratio and DBS less than 0.5. When TOF ratio had recovered to ratio recorded mechanically. The purpose of this more than 0.8, fade was detected only rarely with part of the study was to establish the relationship DBS 3 3 and DBS 44 , while many instances of fade between TOF ratios and the ratios of the DBS could still be felt with DBS 32 and DBS 43 . DBS 3 3 pattern selected in part 1. In 10 patients, paired was considered to be the most useful pattern of twitch recordings of TOF and DBS 3 3 were made the four DBS tested. in one arm during spontaneous recovery of block from a TOF ratio of 0.2 to a TOF ratio of 0.8-0.9. Part 2 TOF was given as the basic pattern of stimulation. For each patient a close linear relationship was At regular intervals (more than every 2 min) a found between TOF ratio and DBS 3 3 ratio. DBS was given in place of TOF stimulation. The There was no significant difference between the response to the last TOF stimulation preceding estimated lines of regression in each patient. The the DBS 3 3 was used for calculation of TOF ratio. observations were pooled and a common linear The DBS ratio was defined as the ratio between regression line was estimated: the height of the second response in relation to that of the first. DBS ratio = 1.07 xTOF ratio-0.032
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
with 66 % nitrous oxide and 0.75-1.5 % halothane in oxygen. Ventilation was controlled to maintain normocapnia. Tracheal intubation was performed following administration of suxamethonium 1.5 mgkg"1 i.v. Pancuronium 1-1.5 mg was given when necessary to maintain neuromuscular block. Following induction of anaesthesia the ulnar nerve of the arm under investigation was stimulated supramaximally at the wrist via cutaneous electrodes connected to either a Myotest nerve stimulator or a computerized unit programmed to deliver TOF stimulations and any combination of DBS. The adduction force of the resultant thumb twitch in response to TOF and DBS stimulation was measured by a force displacement transducer and recorded using a polygraph [2]. The study comprised three parts.
DOUBLE BURST STIMULATION
277
TABLE II. Tactile evaluation of fade in four different DBS responses. Figures indicate the number of instances in which fade was felt in relation to the total number of observations within each interval of true TOF ratios as measured mechanically. Significant differences (P < 0.05) * between DBS3 2 and DBS3 3, and f between DBS, s and DBS3a DBS3 . 3 fade/ total
<0.40 0.41-0.50 0.51-0.60 0.61-0.70 0.71-0.80 0.81-0.90 0.91-1.00
39/39 24/25 15/25 15/34 8/33 0/21 0/22
fade/ total
0/ /o
100 96 60 44 24 0 0
8/8 14/14 10/21 11/24 8/29 1/22 0/11
Standard deviations of regression coefficient (slope) and of the constant (intercept) were 0.03 and 0.08, respectively (fig. 3). Part 3 The twitch height from TOF stimulation was depressed significantly 3 s after a DBS3 3 stimulation. However, at 15 s and 27 s the twitch had increased significantly, although these changes were very small. The TOF ratio increased significantly at 3, 15 and 27 s after DBS stimulation, although changes at 15 and 27 s were minimal (table III). The changes in both twitch 1.00-, 0.80-
S
0.60-
co" W
§
0.40-
A.Q96 P< 0.001
0.20-
0.20
I T 0.40 0.60 TOF ratio
0.80
DBS 1.3
DBS 3.2 0/
/o
100 100 48 46 28 5 0
fade/ total
%
fade/ total
14/14 7/7 18/19 23/24 24/28 15/24 4/12
100 100 95* 96* 86* 63* 33*
9/9 15/17 14/19 17/26 10/20 9/21 0/11
0/ la
100 88 74 65 50
43f 0
height and TOF ratio following DBS3 3 stimulation showed no relationship to the level of block at which DBS was given. DISCUSSION
Our results suggest that residual neuromuscular block can be detected from manual evaluation of the response to a double burst stimulation. The results also suggest that this new pattern of stimulation is more sensitive than the train-offour method used manually. Two of the DBS patterns chosen from the pilot study (DBS 33 and DBS4 4) were found to be similar with regard to the number of cases in which fade was detected at any level of block. At TOF ratios less than 0.5, residual block was identified in almost all cases and at ratios between 0.5 and 0.7 neuromuscular block was judged not to have recovered adequately in 50% of cases. With a true TOF ratio greater than 0.7, residual block was detected only rarely with either DBS3>3 or DBS 44 . In DBS3 2 and DBS 4 3 the degree of DBS fade at any given level of relaxation was enhanced artificially by reducing the number of TABLE III. Change in twitch height {percent of the control twitch height before injection of pancuronium) and TOF ratio {absolute changes) 3, 15 and 27 s after DBS3Z (median (S£>)). All values are significantly different (P < 0.05) from the respective response to the TOF stimulation given 12 s before
1.00
Twitch (%) FIG. 3. Scattergram and regression line of simultaneous TOF TOF ratios v. DBS 3 3 ratios as measured at the same arm. 95% ratio confidence limits are shown.
3s
15 s
27 s
-4.0(4.8)
+1.7(1.8)
+1.1(1.8)
+0.07(0.05)
+0.01(0.02)
+0.01(0.02)
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
True TOF ratio
DBS4 .4
278
magnitude of the fourth response in the TOF was not affected. A small increase in both twitch height and TOF ratio was observed in the second and third TOF responses following DBS 33 . These changes probably result from the slow spontaneous recovery that took place during the procedure. Thus our results suggest that the major post-DBS 33 effect is a depression of only the first twitch in the TOF response. However, this effect is short-lived and neither the twitch nor the ratio in the TOF response was affected when applied 15 s after DBS3 3 stimulation. In conclusion, residual neuromuscular block can be detected from the response to a double burst stimulation. A stimulation pattern of two bursts, each consisting of three impulses given at a frequency of 50 Hz and separated by 750 ms, seems to be the most appropriate for clinical use. The degree of fade in this DBS response and in the TOF response is similar at any level of block. However, although this new pattern of stimulation is apparently more sensitive than the TOF in manual detection of residual block, absence of manual fade in the DBS3 3 response does not exclude residual block. Further clinical studies are needed to delineate more precisely the field of application of DBS. REFERENCES 1. Ali HH, Utting JE, Gray C. Stimulus frequency in the detection of neuromuscular block in humans. British Journal of Anaesthesia 1970; 42: 967-977. 2. Viby-Mogensen J. Clinical assessment of neuromuscular transmission. British Journal of Anaesthesia 1982; 54: 209-223. 3. Viby-Mogensen J, Jensen NH, Engbik J, 0rding H, Skovgaard LT, Chraemmer-Jorgensen B. Tactile and visual evaluation of the response to train-of-four nerve stimulation. Anesthesiology 1985; 63: 440-443. 4. Gissen AJ, Katz RL. Twitch, tetanus and posttetanic potentiation as indices of nerve muscle block in man. Anesthesiology 1969; 30: 481-487. 5. Lee C, Katz RL. Fade of neurally evoked compound electromyogram during neuromuscular block by d-tubocurarine. Anesthesia and Analgesia 1977; 56: 271-275.
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
impulses in the second burst compared with that of the first. This might improve the ability to identify fade manually. Indeed, significantly more cases of fade were found with DBS3 2 compared with DBS3 3 when the TOF ratio was greater than 0.5. The results with DBS4 3 showed the same tendency, although no significant difference was found between DBS4 3 and DBS 33 . However, at TOF ratios greater than 0.7, too many cases of clinically insignificant fade were identified with both DBS, , and DBS 4 ,. Thus with DBS,, and DBS4 3 a false impression of persistent residual block may arise and lead eventually to unnecessary administration or overdoses of an anticholinesterase drug. Consequently, DBS 3 3 and DBS4 4 were chosen as the most suitable and, of the two, DBS3 3 was considered to be the least painful. In a previous study [3] on manual evaluation of the response to TOF stimulation, a method was used similar to that in the present study. The results of the two studies suggest that, when the TOF ratio exceeds 0.4, more instances of fade can be identified with the DBS3 3 method than with TOF. This, in combination with our observation that the degree of fade in DBS3 3 and in TOF is similar at any level of block, supports our hypothesis that the presence of the second and third responses in TOF impede manual identification of fade. The tetanic fade and post-tetanic facilitation seen during and following, for example, a 50-Hz tetanus for 5 s is well-known [4]. However, a single stimulus is sufficient to elicit measurable fade or measurable facilitation of the following responses during neuromuscular block [5]. The degree of both depends upon the frequency with which the following stimulations are applied [5], but facilitation following a single stimulus is apparently a process of shorter duration than that leading to fade. Thus the DBS3 3 was expected to influence the response of the succeeding TOF stimulations. A characteristic depression of the first twitch in the TOF response was observed 3 s after DBS3 3. However, the ratio of the TOF response was increased, as the
BRITISH JOURNAL OF ANAESTHESIA
DOUBLE BURST STIMULATION (DBS): A NEW PATTERN OF NERVE STIMULATION TO IDENTIFY RESIDUAL NEUROMUSCULAR BLOCK J. ENGB^EK, D. 0STERGAARD AND J. VIBY-MOGENSEN
SUMMARY We present a new pattern of nerve stimulation— double burst stimulation (DBS)—to detect residua/ neuromuscular block manually. The DBS consists of two short lasting, 50-Hz tetanic stimuli or bursts separated by a 750-ms interval. The response to this pattern of stimulation is two single separated muscle contractions of which the second is less than the first during nondepolarizing neuromuscular blockade. The ability to identify fade manually at different train-offour (TOF) ratios was compared in four DBS patterns in which different numbers of impulses in the individual bursts were combined. The DBS with three impulses in each burst (DBS3i3) was considered to be the most sensitive and the least painful and thus most suitable for clinical use. The degree of fade in TOF and DBS33 was almost identical at any level of blockade (correlation coefficient 0.96), and the major post-DBS 33 effect was a depression of the first twitch in TOF lasting less than 15 s. It is concluded that the DBS is more sensitive than the TOF in manual detection of residual block.
MATERIAL AND METHODS
Principle of double burst stimulation
Double burst stimulation consists of two short tetanic stimulations (bursts) separated by a short interval (fig. 1). If the frequency of the tetanic stimulation is not too low (i.e. ^ 30-40 Hz) and if the interval between the two bursts is not too short, the response to this stimulation pattern is two single separate muscle contractions. During JENS ENGBAK, M.D.; DORIS OSTERGAARD, M.D.; JBRGEN VIBY-
MOGENSEN, M.D., PH.D. ; Department of Anaesthesia, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. Accepted for Publication: July 5, 1988.
non-depolarizing neuromuscular block the response to the second burst of stimulation is less than that to the first, corresponding with fade to the TOF response (fig. 2). We postulated that any difference in the two responses in DBS was felt more easily than the difference between the first and the fourth response to TOF nerve stimulation. Different patterns of DBS can be designed from different combinations of three variables in the stimulation pattern: the frequency of tetanic stimulation, the duration of tetanic stimulation,
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
The. degree of residual neuromuscular block during recovery from non-depolarizing muscle relaxant drugs is evaluated normally from the response to train-of-four (TOF) nerve stimulation [1,2]. However, without quantitative recording of the evoked response it is difficult to estimate the TOF ratio. Thus when the TOF ratio has recovered to more than 0.4—0.5, fade in the response cannot be identified manually with sufficient accuracy to exclude residual curarization [3]. One reason for this may be that the two middle responses to TOF stimulation confound the estimation of the last response in relation to the first. Therefore, we postulated that a pattern of stimulation resulting in only two muscle contractions, but stressing the neuromuscular junction to the same extent as TOF stimulation, might improve the ability to identify fade manually. The purpose of this study was to evaluate if the use of two short lasting tetanic stimuli separated by a short interval—double burst stimulation (DBS)—can be used to diagnose residual neuromuscular block manually.
275
DOUBLE BURST STIMULATION
UUI
TABLE I. Different combinations of frequency and number of impulses in the first and the second burst of the DBS used in the pilot study. The interval between the bursts was 750 ms. DBS33, DBSi 4) DBS31, and DBSi3 are indicated. See text for further explanation Tetanic frequency
No. of impulses
20 ms DBS
750 ms
and the interval separating the two tetanic stimulations. However, the number of possible combinations of these variables is restricted and the frequency of the tetanic stimulation must exceed 30-40 Hz so that the muscle response to the stimuli in the burst fuses. On the other hand, to minimize the pain caused by stimulation, a frequency as low as possible should be chosen. The duration of the bursts also has to be short (two-to-four impulses) so that the muscle response is felt as a single short lasting contraction and not as a sustained response. The duration of the muscle contraction following such bursts is approximately 400-500 ms. Therefore, to have the two muscle responses clearly separated in the DBS, the interval between the individual bursts should be longer than the 500 ms separating the impulses in the TOF. Preliminary studies
In preliminary studies, nine different patterns of DBS were investigated (table I). On the basis of how easily fade was detected manually at different levels of block, a limited number of combinations of the variables were selected for further clinical 10s
FIG. 2. Mechanical twitch recording of a DBS 3 3 (at arrow). Notice that the degree of fade in the DBS response corresponds to the degree of fade in the TOF response.
DBS 3 , DBS 44 DBS 32 DBS 4 3
Burst 2
Burst 1
Burst 2
100 100 100 50 50 50 50 50 50
100 50 50 50 50 50 50 50 100
2 3 3 2 3 4 3 4 3
2 3 2 2 3 4 2 3 2
study. It was found that the major determinant of the response to DBS was the duration of the tetanic stimulation—that is, the number of impulses and not the frequency (50 or 100 Hz) used in the bursts. Further, if identical frequencies but different durations were used, a more pronounced difference between the two responses to DBS was felt. To have the muscle contractions separated as clearly as in the TOF response, an interval of 750 ms was selected in all DBS patterns used. Based on the results of these preliminary studies, four different patterns of DBS were selected for further clinical evaluation (table I). All the DBS patterns selected included the use of a 50-Hz tetanic stimulation. In DBS3 3 and DBS4 4, three and four impulses, respectively, were given in each tetanic burst. In DBS3 2 three impulses were given in the first burst and only two in the last; in DBS4 3 there were four and three impulses, respectively. Design of the main study
We studied 41 adult patients (ASA physical status I or II) undergoing elective gynaecological or gastroenterological surgery. None of the patients suffered from neuromuscular disease or received any drug that might alter neuromuscular function. The study was approved by the local Ethics Committee, but informed consent was not obtained as the anaesthetic and monitoring procedures were those used in standard practice. One hour after administration of diazepam 0.2 mg kg"1 by mouth, anaesthesia was induced with thiopentone 3-5 mg kg"1 i.v. and maintained
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
FIG. 1. Stimulation pattern in double burst stimulation (DBS). The time constants given are those of a DBS3 3. In each burst three impulses are given at a frequency of 50 Hz (one impulse every 20 ms). The two bursts are separated by 750 ms. See text for further explanation.
Burst 1
276
BRITISH JOURNAL OF ANAESTHESIA Part 3. Decurarizing effect of Z>BS33. The purpose of this study was to investigate a possible decurarizing effect of DBS stimulation. In seven patients, both the height of the first response in the TOF and the TOF ratio obtained from mechanical twitch recordings 3, 15 and 27 s after DBS3 3 were compared with the twitch height and the TOF ratio of the last TOF response preceding the DBS 3 3 during spontaneous recovery of the block. TOF and DBS stimulation were given as described in part 2. For statistical evaluation, Fisher's exact probability test, Chi-square test for two independent samples, Wilcoxon matched pairs signed ranks test, Student's t test and analyses of linear regression (least square methods) were used.
Part 1. Manual evaluation of DBS. The purpose of this part of the study was to investigate the four DBS patterns chosen from the pilot study in order to select the DBS with the highest sensitivity. In 24 patients the mechanical twitch was measured from one arm (the control arm) during TOF stimulation. On the other arm (the test arm) TOF stimulation was given as the basic pattern of stimulation. At regular intervals (more than every 2 min) a DBS stimulation was given in place of TOF stimulation. The four DBS (DBS 33 , DBS 44 , DBS3 2, and DBS4 3) were given in random order during spontaneous recovery of the block. The response to the selected DBS was evaluated manually by two observers without access to the TOF ratio measured in the control arm. The observers had to decide if fade was present in the DBS response.
RESULTS
Part 1 Table II shows the number of instances in which fade was felt in the four different DBS responses at different TOF ratios. The results obtained with DBS3>3 in the preliminary study and in part 1 were not statistically different and therefore were pooled. Thus the response to DBS3>3, DBS 44 , DBS 32 , and DBS 4 3 were evaluated 199, 129, 128 and 123 times, respectively. There was no statistically significant difference between DBS 3 3 and DBS 44 at any TOF ratio. Significantly more examples of fade were identified with DBS3 2 compared with DBS 3 3 when the TOF ratio was above 0.5. In the interval 0.81-0.90, a statistically significant difference was found also between DBS3 3 and DBS4 3. Generally, with any of the DBS selected, only few cases of fade were not felt when TOF ratio was Part 2. Relation between TOF ratio and DBS less than 0.5. When TOF ratio had recovered to ratio recorded mechanically. The purpose of this more than 0.8, fade was detected only rarely with part of the study was to establish the relationship DBS 3 3 and DBS 44 , while many instances of fade between TOF ratios and the ratios of the DBS could still be felt with DBS 32 and DBS 43 . DBS 3 3 pattern selected in part 1. In 10 patients, paired was considered to be the most useful pattern of twitch recordings of TOF and DBS 3 3 were made the four DBS tested. in one arm during spontaneous recovery of block from a TOF ratio of 0.2 to a TOF ratio of 0.8-0.9. Part 2 TOF was given as the basic pattern of stimulation. For each patient a close linear relationship was At regular intervals (more than every 2 min) a found between TOF ratio and DBS 3 3 ratio. DBS was given in place of TOF stimulation. The There was no significant difference between the response to the last TOF stimulation preceding estimated lines of regression in each patient. The the DBS 3 3 was used for calculation of TOF ratio. observations were pooled and a common linear The DBS ratio was defined as the ratio between regression line was estimated: the height of the second response in relation to that of the first. DBS ratio = 1.07 xTOF ratio-0.032
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
with 66 % nitrous oxide and 0.75-1.5 % halothane in oxygen. Ventilation was controlled to maintain normocapnia. Tracheal intubation was performed following administration of suxamethonium 1.5 mgkg"1 i.v. Pancuronium 1-1.5 mg was given when necessary to maintain neuromuscular block. Following induction of anaesthesia the ulnar nerve of the arm under investigation was stimulated supramaximally at the wrist via cutaneous electrodes connected to either a Myotest nerve stimulator or a computerized unit programmed to deliver TOF stimulations and any combination of DBS. The adduction force of the resultant thumb twitch in response to TOF and DBS stimulation was measured by a force displacement transducer and recorded using a polygraph [2]. The study comprised three parts.
DOUBLE BURST STIMULATION
277
TABLE II. Tactile evaluation of fade in four different DBS responses. Figures indicate the number of instances in which fade was felt in relation to the total number of observations within each interval of true TOF ratios as measured mechanically. Significant differences (P < 0.05) * between DBS3 2 and DBS3 3, and f between DBS, s and DBS3a DBS3 . 3 fade/ total
<0.40 0.41-0.50 0.51-0.60 0.61-0.70 0.71-0.80 0.81-0.90 0.91-1.00
39/39 24/25 15/25 15/34 8/33 0/21 0/22
fade/ total
0/ /o
100 96 60 44 24 0 0
8/8 14/14 10/21 11/24 8/29 1/22 0/11
Standard deviations of regression coefficient (slope) and of the constant (intercept) were 0.03 and 0.08, respectively (fig. 3). Part 3 The twitch height from TOF stimulation was depressed significantly 3 s after a DBS3 3 stimulation. However, at 15 s and 27 s the twitch had increased significantly, although these changes were very small. The TOF ratio increased significantly at 3, 15 and 27 s after DBS stimulation, although changes at 15 and 27 s were minimal (table III). The changes in both twitch 1.00-, 0.80-
S
0.60-
co" W
§
0.40-
A.Q96 P< 0.001
0.20-
0.20
I T 0.40 0.60 TOF ratio
0.80
DBS 1.3
DBS 3.2 0/
/o
100 100 48 46 28 5 0
fade/ total
%
fade/ total
14/14 7/7 18/19 23/24 24/28 15/24 4/12
100 100 95* 96* 86* 63* 33*
9/9 15/17 14/19 17/26 10/20 9/21 0/11
0/ la
100 88 74 65 50
43f 0
height and TOF ratio following DBS3 3 stimulation showed no relationship to the level of block at which DBS was given. DISCUSSION
Our results suggest that residual neuromuscular block can be detected from manual evaluation of the response to a double burst stimulation. The results also suggest that this new pattern of stimulation is more sensitive than the train-offour method used manually. Two of the DBS patterns chosen from the pilot study (DBS 33 and DBS4 4) were found to be similar with regard to the number of cases in which fade was detected at any level of block. At TOF ratios less than 0.5, residual block was identified in almost all cases and at ratios between 0.5 and 0.7 neuromuscular block was judged not to have recovered adequately in 50% of cases. With a true TOF ratio greater than 0.7, residual block was detected only rarely with either DBS3>3 or DBS 44 . In DBS3 2 and DBS 4 3 the degree of DBS fade at any given level of relaxation was enhanced artificially by reducing the number of TABLE III. Change in twitch height {percent of the control twitch height before injection of pancuronium) and TOF ratio {absolute changes) 3, 15 and 27 s after DBS3Z (median (S£>)). All values are significantly different (P < 0.05) from the respective response to the TOF stimulation given 12 s before
1.00
Twitch (%) FIG. 3. Scattergram and regression line of simultaneous TOF TOF ratios v. DBS 3 3 ratios as measured at the same arm. 95% ratio confidence limits are shown.
3s
15 s
27 s
-4.0(4.8)
+1.7(1.8)
+1.1(1.8)
+0.07(0.05)
+0.01(0.02)
+0.01(0.02)
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
True TOF ratio
DBS4 .4
278
magnitude of the fourth response in the TOF was not affected. A small increase in both twitch height and TOF ratio was observed in the second and third TOF responses following DBS 33 . These changes probably result from the slow spontaneous recovery that took place during the procedure. Thus our results suggest that the major post-DBS 33 effect is a depression of only the first twitch in the TOF response. However, this effect is short-lived and neither the twitch nor the ratio in the TOF response was affected when applied 15 s after DBS3 3 stimulation. In conclusion, residual neuromuscular block can be detected from the response to a double burst stimulation. A stimulation pattern of two bursts, each consisting of three impulses given at a frequency of 50 Hz and separated by 750 ms, seems to be the most appropriate for clinical use. The degree of fade in this DBS response and in the TOF response is similar at any level of block. However, although this new pattern of stimulation is apparently more sensitive than the TOF in manual detection of residual block, absence of manual fade in the DBS3 3 response does not exclude residual block. Further clinical studies are needed to delineate more precisely the field of application of DBS. REFERENCES 1. Ali HH, Utting JE, Gray C. Stimulus frequency in the detection of neuromuscular block in humans. British Journal of Anaesthesia 1970; 42: 967-977. 2. Viby-Mogensen J. Clinical assessment of neuromuscular transmission. British Journal of Anaesthesia 1982; 54: 209-223. 3. Viby-Mogensen J, Jensen NH, Engbik J, 0rding H, Skovgaard LT, Chraemmer-Jorgensen B. Tactile and visual evaluation of the response to train-of-four nerve stimulation. Anesthesiology 1985; 63: 440-443. 4. Gissen AJ, Katz RL. Twitch, tetanus and posttetanic potentiation as indices of nerve muscle block in man. Anesthesiology 1969; 30: 481-487. 5. Lee C, Katz RL. Fade of neurally evoked compound electromyogram during neuromuscular block by d-tubocurarine. Anesthesia and Analgesia 1977; 56: 271-275.
Downloaded from http://bja.oxfordjournals.org/ at Karolinska Institutet on July 15, 2015
impulses in the second burst compared with that of the first. This might improve the ability to identify fade manually. Indeed, significantly more cases of fade were found with DBS3 2 compared with DBS3 3 when the TOF ratio was greater than 0.5. The results with DBS4 3 showed the same tendency, although no significant difference was found between DBS4 3 and DBS 33 . However, at TOF ratios greater than 0.7, too many cases of clinically insignificant fade were identified with both DBS, , and DBS 4 ,. Thus with DBS,, and DBS4 3 a false impression of persistent residual block may arise and lead eventually to unnecessary administration or overdoses of an anticholinesterase drug. Consequently, DBS 3 3 and DBS4 4 were chosen as the most suitable and, of the two, DBS3 3 was considered to be the least painful. In a previous study [3] on manual evaluation of the response to TOF stimulation, a method was used similar to that in the present study. The results of the two studies suggest that, when the TOF ratio exceeds 0.4, more instances of fade can be identified with the DBS3 3 method than with TOF. This, in combination with our observation that the degree of fade in DBS3 3 and in TOF is similar at any level of block, supports our hypothesis that the presence of the second and third responses in TOF impede manual identification of fade. The tetanic fade and post-tetanic facilitation seen during and following, for example, a 50-Hz tetanus for 5 s is well-known [4]. However, a single stimulus is sufficient to elicit measurable fade or measurable facilitation of the following responses during neuromuscular block [5]. The degree of both depends upon the frequency with which the following stimulations are applied [5], but facilitation following a single stimulus is apparently a process of shorter duration than that leading to fade. Thus the DBS3 3 was expected to influence the response of the succeeding TOF stimulations. A characteristic depression of the first twitch in the TOF response was observed 3 s after DBS3 3. However, the ratio of the TOF response was increased, as the
BRITISH JOURNAL OF ANAESTHESIA