JOURNAL

OF APPLIED

PHYSIOLOGY

Vol. 39, No. 5, November

1975.

Tetanic

force

pollicis

muscle NAOSUKE Research

Printed in U.S.A.

development in anesthetized

SUGAI, Dep(lrtment

St. Peter’s

Hosfu’ta/,

of adductor

RONALD of Anaesthetics,

London,

KC2,

WORSLEY, Royal

College

AND J. P. PAYNE of Surgeons of England und

England

before the start of urological surgery after their informed consent had been obtained on the previous day. Anesthesia was induced with halothane, nitrous oxide, and oxygen. Endotracheal intubation was performed without the use of a neuromuscular blocking agent after spraying the larynx with a 4 % lidocaine solution. Halothane was then discontinued and anesthesia was maintained with nitrous oxide, oxygen, and intravenous Demerol (50-100 mg in 1 h in divided doses). The force of the tetanic contraction of the adductor pollicis muscle was measured by a Statham force transducer model UC with a load cell model UL-4-20 incorporated in a handgrip (13). The frequency response of the transducer with the load cell was flat from 0 to 90 Hz. At least 30 min passed after the cessation of halothane administration before the ulnar nerve stimulation was started. Electrical stimulation of the ulnar nerve was performed by means of a Device’s stimulator type 3072 with an isolation unit and a digitimer type 3290 through platinum needle electrodes inserted at the wrist. The tetanic stimulation was generated in conjunction with a gated pulse generator type 252 1. Tetanic stimulation of the ulnar nerve supplying the hand on which the transducer was mounted was first oerformed at a frequency of 50 Hz lasting for 1 s at 12-s intervals. The voltage was adjusted so that it could give a supramaximal stimulation at 50 Hz and stimulation was continued with this frequency for 1 s every 12 s. The frequency of 50 Hz was selected because it is commonly used in clinical situations. The l-s duration of application of the stimulus was chosen on the basis that even when fusion had not occurred at low frequencies a definite plateau pattern was recognisable in less than 0.5 s (Fig. 1). After a control period of about 10 min, the frequency of the tetanic stimulation was altered in steps from 10 to 100 Hz. When the frequency of stimulation was increased from the initial 10 to 50 Hz, each increment was 5 Hz, but when the shift was from 50 to 100 Hz the increment was 10 Hz. Thus 14 different frequencies were applied between 10 and 100 Hz as tetanic stimuli. Each frequency was applied at 12-s intervals and each tetanic stimulation lasted for one second. The duration of each single component of tetanic stimulation was 200 pus. Throughout the study respiration was controlled by the use of a Manley ventilator and arterial blood gases were maintained within normal limits. For this purpose blood samples were taken from the radial artery of the free arm

SUGAI, NAOSUKE, RONALD WORSLEY, AND J. P. PAYNE. Tetanic force development of adductor Polk’s muscle in anesthetized man. J. Appl. Physiol. 39(5) : 7 14-7 17. 1975.-The tetanic force development of the human adductor pollicis muscle was studied under light anesthesia with nitrous oxide, oxygen, and Demerol, by the use of tetanic stimulation of the ulnar nerve at frequencies ranging from 10 to 100 Hz. The time necessary for the tetanic contraction to reach a plateau was longest at frequencies between 15 and ‘20 Hz. Fusion of tetanus occurred between 40 and 45 Hz. The mean maximal force of 6.92 kg was developed at a mean frequency of approximately 75 Hz. The maximal force was well maintained up to a stimulation frequency of 100 Hz. The results indicate that in lightly anesthetized man, the maximal force is developed at higher stimulation frequencies than those observed in conscious man and that it is well sustained at higher frequencies.

ulnar nerve tetanic-tension

stimulation; ratio

fusion

of tetanus;

maximal

tetanic

force;

THE TETANIC ADDUCTION of the thumb in man elicited by the electrical stimulation of the ulnar nerve can be regarded as the tetanic contraction of the adductor pollicis muscle and is an important parameter often used for the assessment of neuromuscular blockade during anesthesia (4, 6, 7, 9). To utilize this tetanic contraction effectively, it is necessary to know the point of fusion of the repetitive tetanic contractions and the changing pattern of the tetanic force development when the frequency of the electrical stimulation is altered in a stepwise fashion. Earlier studies on the changing patterns of tetanic contraction of skeletal muscle with different stimulation frequencies were concerned either with conscious subjects (1, 11) or with animals (3). Electrical stimulation of the ulnar nerve at high frequencies is painful for conscious subjects and the responses obtained in such subjects may differ from those in anesthetized man. This study was undertaken to evaluate the changes in the pattern of tetanic-force development of the thumb in man under light general anesthesia when the frequencies of ulnar nerve stimulation were altered by steps. The patients were anesthetized with nitrous oxide, oxygen, and intravenous Demerol and studied under controlled conditions. SUBJECTS

AND

man

METHODS

Nineteen male adult patients ranging in age from 38 to 86 yr with a mean age of 60.7 =t 10.8 (SD) were studied 714

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TETANIC

CONTRACTIONS

OF

ADDUCTOR

715

POLLICIS

r

0

I

I TIME

1. Response corresponding ulnar In this particular above 40 Hz. FIG.

of adductor nerve for experiment

I

0

(s)

pollicis muscle to stimulation 1 s at a series of different frequencies. the tracings were virtually identical

of

and analysed at regular intervals. Recordings were made on a Brush-Clevite recorder at a slow speed of 5 mm/min and on a Mingograf recorder at a fast speed of 50 mm/s. The frequency response of the Mingograf recorder was flat from 0 to 500 Hz. Analysis of the data was made on the record taken by the Mingograf recorder at a paper speed of 50 mm/s. Measurements were made by hand on this record, but all the subsequent calculations and the derivation of the maximal 011 a PDP 12 digital computer. force were performed RESULTS

Time interval between beginning of contraction to initial plateau of tetanic force developed. The time interval from the beginning of the tetanic contraction to the initial plateau of the force developed was measured and expressed in milliseconds. Figure 2 shows the relationship between the frequency of stimulation and this time interval seen in one patient. In general, the time interval was maximal between the frequencies of 15 and 20 Hz and thereafter decreased and remained at a lower level than the time interval necessary to reach a plateau at 10 Hz. The mean of the maximal time intervals seen in all 19 patients was 468 & 48 (SD) ms. Table 1 lists, in each patient, the frequency at which the time interval to plateau was the highest and the corresponding maximal time interval in milliseconds. The time intervals necessary to reach the plateaux at 10 and 100 Hz were compared with the maximal time intervals and expressed as a percentage for each patient. The mean percentage time interval at 10 Hz was 83.9 =t 14.4 which was significantly larger (P < 0.01) than the mean percentage time interval of’ 71.5 & 9.5 at 100 Hz. Determination of frequency of stimulation at which fusion of

of stimulation mechanitetanus occurred. At low frequencies cal fusion was incomplete so that the response to each individual stimulus in the train could be identified as an undulation on the fast recording (Fig. 1). The degree of fusion was calculated by measuring the height above the base line of the particular undulation that coincided with the beginning of the plateau and expressing it as a percentage of the peak tetanic contraction. The fusion of the tetanus was regarded as complete when the undulations disappeared from the contraction record on the fast tracting. The relationship between the degree of fusion and the frequencies tested is illustrated in Fig. 1. Fusion occurred between 45 and 50 Hz in eight patients, between 40 and 45 Hz in eight patients, between 35 and 40 Hz in two patients, and between 30 and 35 Hz in one patient. Thus in more than 80 7c of the patients studied the fusion of the tetanus occurred between 40 and 50 Hz. Determination of maximal force developed in response to tetanic stimulation. The initial peak force was determined when the tetanic force development reached a plateau, and again at the end of the tetanic contraction which lasted for 1 s. The tetanic-tension ratio was expressed as a percentage of the force at the end of the tetanus compared with the initial peak force as previously described (4) and illustrated in Fig. 3. The maximal force was determined by comparing the tetanic forces developed in response to different frequencies of stimulation. The frequency at which this maxima1 force developed was also recorded. When the maximal force was recorded at more than two different frequencies of stimulation the lower frequency was taken as the point where the maximal force developed. (In three patients the maximal force exceeded the ideal linearity range of the transducer used but each value was within the reasonable range of the performance of the transducer.) The maximal force developed for each patient, the frequency of stimulation at which the maximal force developed, and the tetanictension ratio of this maximal force are listed in Table 1. The maximal force was developed at the mean frequency of 75.9 zt 16.4 (SD) H z and the mean maximal force was 6.92 z!= 2.57 kg. The mean tetanic-tension ratio of the maximal force developed was 99.1 & 1.O %, demonstrating that the tetanic tension was well maintained at the maximal force. The tetanic-tension ratios with the force at 100 Hz had a mean value of 98.7 & 1 .O %. The mean value of the tetanic force at 100 Hz was 99.2 & 1.8 76 of the maximal force, showing that the maximal force was well maintained up to 100 Hz of tetanic stimulation. Figure 4 shows the initial peak force corresponding to each different frequency of stimulation. DISCUSSION The response of the adductor pollicis muscle to tetanic stimulation below 20 Hz is slow to develop. Fatigue of muscle might be expected with these intermediate fresince the muscle has to make quencies of stimulation, gross rapid movements instead of a uniformly sustained tetanus. For this reason, stimulation in this frequency range might be less acceptable for the study of tetanic contractions. Not unexpectedly as the stimulation frequency was raised the time interval to reach a tetanic plateau decreased and at 100 Hz was significantly shorter than at 10 Hz.

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716

SUGAI,

WORSLEY,

AND

PAYNE

FIG. 2. Relationship between frequency of stimulation and time interval from beginning of contraction to plateau of force development.

r

I

20

30

I

I

40 FREQUENCY

I

50 60 OF TETANIC

I

70 STIMULATION

I

80

I

90

1

100

TABLE 1. Relationship between frequency of tetanic stimulation and mode of force development _-.-~-_ _ ~_---~ --~-~--._--_ _____. ~~~~--__--___ . Pat1ents

Frequency at Which Maximal Time to Peak Occurred, Hz

Fn$:’

Maximal

PeakJ ms

kg,

Force.

--

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Mean

~-~

’

Frequency at Which Maximal Force Developed, Hz

TTR of Maxima1 Force, y0 ~~

15 15 15 80 50 10 15 15 15 15 15 10 10 15 15 20 10 15 20

480 560 520 440 460 500 520 540 420 480 440 500 400 440 480 480 440 400 400

7.70 2.05 9.34 5.90 4.18 5.65 4.93 2.38 5.68 9.37 10.37 5.92 6.86 7.67 11.29 10.08 7.80 8.33 6.01

80 45 80 45 60 90 80 80 100 60 80 100 70 70 100 90 70 70 70

96.9 100.0 100.0 100.0 100.0 100.0 100.0 99.2 97.7 98.8 97.5 98.1 99.2 99.6 98.4 100.0 99.6 98.9 99.6

19.7zk17.0

468zt48

6.92zk2.57

75.9zk16.4

99.lzkl.O

zt SD ____---__~.

_

Frequency expressed

is expressed as a percentage.

in

Hz.

TTR

=

-. ___~ tetanic-tension

ratio,

In an early study in cats, Cooper and Eccles (3) measured the frequency of stimulation necessary for a complete mechanical fusion of the force developed by various skeletal muscles. They found high values for extensor digitorum long-us (115 Hz) and gastrocnemius (100 Hz) muscles compared with a relatively low value for soleus (33 Hz). The highest value (350 H z ) was obtained for the internal rectus of the eye. Compared with the cat extensor digitorum longus, the adductor pollicis muscle in man seems to be less capable of responding to high frequencies of tetanic stimulation. The fusion of tetanus can be partly determined by the duration of the active state of the individual twitch (8). When repeated stimuli are applied the duration of the active state :I: Jst be less than the time between stimuli for the muscle tensions elicited in response to these stimuli to be separated from each other. Several workers have attempted to estimate the duration of the active state by observing

A7

x

loo

--

T.T.R.

=

T.T.R.

L

TB3 FIG.

calculating tracing obtained blocking

3. Response of adductor pollicis A, time to plateau, B, tetanic which illustrates the presence from a patient recovering from agent .

%uOO=TTR . *. A3 T=

TIME

TO

PLATEAU

muscle to show method of tension ratio (TTR). Lowest of tetanic-tension fade was the effect of a neuromuscular

the separation of the force curves in response to repetitive stimuli (2, 10, 12). H owever, Wilander (14) reported that in the rat gastrocnemius muscle, the stimulation interval just necessary for fusion of an isometric tension plateau is more than twice as long as the longest possible duration of the active-state plateau for shortening after a single impulse. In the present study the determining factor in the fusion of the tetanus is probably not the duration of the active state but the anatomical structures involved in the adduction of the thumb. The tetanic fusion of the adductor pollicis muscle occurred at a stimulation frequency between 40 and 50 Hz in lightly anesthetized man and the maximal force developed at a frequency of 75 Hz. This maximal force was well maintained until tetanic stimulation reached 100 Hz. These findings suggest that the adductor pollicis muscle in man can respond to a much higher frequency of tetanic stimulation than has been observed in previous studies in conscious subjects. Merton (11) showed that in conscious subjects the force of the tetanic contraction of the adductor pollicis muscle reached a plateau at a tetanic stimulation of 50 Hz. In another study in conscious subjects, &gland and Lippold (1) showed that the adductor pollicis produced maximal force at a tetanic stimulation between 25 and 40 Hz. The same workers also showed that above a frequency of 35-40 Hz the tetanic force development decreased as the frequency of stimulation was raised.

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TETANIC

CONTRACTIONS

OF

ADDUCTOR

717

POLLICIS

FIG. 4. Relationship between quency of stimulation and initial force of tetanic contractions.

3-9 f 10

I 20

I 30

I 40 FREQUENCY

I 50 OF

I 60 70 TETANIC STIMULATION I

In the present study, however, the maximal force developed at much higher frequencies of stimulation than those found in these previous studies. The tetanic tension was well maintained and the maximal force was also well maintained with frequencies up to 100 Hz, although a slight decrease in the tetanic-tension ratio was observed in the top range. The diff’erence observed between conscious and lightly anesthetized subjects might have resulted from the voluntary control of the thumb in conscious subjects because of the pain produced by stimulation at high frequencies. Ehnqvist and Quastel (5) described the effects of tetanic stimulation and of calcium and magnesium on transmitter release from the motor nerve terminal when isolated human intercostal muscle was studied. Thev found that the rate at which the transmitter is released from the motor nerve terminals increases with increasing frequency of stimulation and approaches maximal at a stimulation frequency of about 70 Hz and this rate of release is maintained until 100 Hz. Since the frequency at which the adductor produced the maximal force was approxipollicis r~lusclc mately at this level in our study this might support our contention that the human adductor pollicis muscle produces maximal force at a higher frequency of stimulation than that found previously in conscious subjects. Tetanic contractions of the thumb have been used previously (4, 6, 7, 9) in studying neuromuscular blockade in

I

I

80

frepeak

I

90

100

man. In these studies frequencies less than 40 Hz have often been employed to test the response of the thumb to tetanic stimulation. These lower frequencies are less dernanding on neuromuscular transmission and might provide good reason for employing such frequencies if fatigue of transmission is to be avoided. However, if well sustained and completely fused tetanic contractions of the thumb are to be tested, frequencies above 50 Hz are recornrnended on the basis of the experiments described. In this study it has been demonstrated that the frequency of tetanic stimulation at which complete fusion of the tetanus of the adductor pollicis muscle occurs is around 40-50 Hz in lightly anesthetized man. The rnaxirnal force of tetanic contraction of the adductor pollicis occurred at a frequency of approxirnately 75 Hz which is higher than the values previously observed in conscious subjects. Tetanus was well maintained at this point and the maximal force was also well rnaintained up to a frequency of 100 Hz. We are indebted to Mrs. Jennifer Eccles SRN for technical assistance, to hlr. R. Bartholomew and his staff for the illustrations, to our surgical and nursing colleagues for their tolerance and patience, and to our volunteers without whom the study would have been impossible. Naosuke Sugai was the holder of a Wellcome-Japanese Travelling Research Fellowship while this work was being carried out. Received

for

publication

3 March

I

1975.

REFERENCES 1. BIGLAND, B., AND 0. C. J. LIPPOLD. RIotor unit activity in the voluntary contraction of human rnrde. J. Physiol., London 125 : 322-335, 1954. 2. BULLER, A. J., AND D. hf. LEWIS. The rate of tension development in isometric tetanic contractions of mammalian fast and slow skeletal muscle. J. Physiol., London 176: 337-354, 1965. S., AND J. C. ECCLES. The isometric responses of mam3. COOPER, malian muscles. J. Physiol., London 69 : 377-385, 1930. 4. DE JONG, R. H., AND F. G. FREUND. Characteristics of the neuromuscular block with succinylcholine and decamethonium in man. Anesthesiology 28 : 583-59 1, 1967. D., AND D. Al. J. QUASTEL. A quantitative study of 5. ELMQVIST, end-plate potentials in isolated human muscle. J. Physiol., London 178 : 505-529, 1965. A. J., AND R. L. KATZ. Twitch, tetanus and posttetanic 6. GISSEN, potentiation as indices of nerve-muscle block in man. Anesthesiology 30: 481-487, 1969. D. V., Y. SKOVSTED, AND P. J. COHEN. The effects 7. HEISTERKAMP, of small incremental doses of d-tubocurarine on neuromus-

11.

cular transmission in anesthetized man. Anesthesiology 30 : 500505, 1969. HILL, A. V. The abrupt transition from rest to activity in muscle. Proc. Roy, SOL., London, Ser. B 136 : 399-420, 1949. KATZ, R. L. Electromyographic and mechanical effects of suxamethonium and tubocurarine on twitch, tetanic and post-tetanic responses. Brit. J. Anaesthesia 45 : 849-859, 1973. MACPHERSON, L., AND D. R. WILKIE. The duration of the active state in a muscle twitch. J. Physiol., London 124: 292-299, 1954. MERTON, P. A. Voluntary strength and fatigue. J. Physiol., London

12.

123: 533-564, SANDOW, A.,

8. 9.

10.

netics Proc. 13. 14.

1954. AND G.

of active state 12: 123, 1953.

E.

MAURIELLO.

in

muscular

TYRRELL, R/I. F. The measurement tion. Anaesthesia 24 : 626-629, 1969. WILANDER, B. Active state durations Acta

Physiol.

&and.

68 : l- 17,

Fusion tetanus of the of rat

frequency, (Abstract).

force

of thumb

gastrocnemius

the

ki-

Federation adducmuscle.

1966.

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