Method and apparatus for monitoring and/or controlling the neuromuscular blocking, specially the blocking produced by muscular relaxing pharmaceuticals during anaesthesia

The method consists in the stimulation of a nerve and the detection and measurement of the response and is characterized in that the nerve stimulation is done in the skin which covers the muscles on which the detection of the response is performed. The apparatus comprises means for the application of the nerve stimulation, means for the detection of the response and, optionally, means for the monitoring of the neuromuscular block, and it is characterized in that said means are provided in a single body, which is a cuff of the type used for measuring arterial pressure, provided with means for a detection of pressure or connected to said means. It is not necessary to stimulate any peripheral nerves, and the apparatus is more compact and handy.

The present invention pertains to a device for the monitoring and/or 
controlling of the neuromuscular block, especially that produced by muscle 
relaxant drugs used during anaesthesia. 
Primarily, the new method and apparatus allow a quantification and control 
of the neuromuscular block by means of transcutaneous stimulation directly 
on the muscle, stimulating the intramuscular nerve pathways and the neural 
part of the motor plate without the need of having to stimulate a 
peripheral motor nerve. 
The invention also allows a controlled administration of the blocker drug 
during the induction of the anaesthesia, as well as control of the 
neuromuscular block during the operation and control of the recovery when 
being awakened from the anaesthesia. 
ANTECEDENTS OF THE INVENTION 
It is known that major advances in surgery have come about from the 
application of muscle relaxant drugs during anaesthesia, which in addition 
to facilitating the work of the surgeon also allows a less traumatic 
intubation and facilitates mechanical respiration. 
Likewise, muscle relaxation allows improved mechanical ventilation for 
intubated patients at intensive care wards. 
It is also known that there are various factors which influence the 
duration and effect of the muscle relaxants, depending among other things 
on the body weight, the age, the physical condition and possible 
pathologies of the patient to whom this type of drug is being 
administered. In the event that the dose is insufficient, the intubation 
and the subsequent surgery might become more difficult; in the case of 
overdosage, the patient upon awakening from the anaesthesia might present 
respiratory insufficiency and a need for prolonged artificial respiration, 
which would delay their leaving the operating theater or their admission 
to a special care ward. 
Other dangers of overdosage or poor reversal of the effects of muscle 
relaxants might be serious complications such as aspiration of vomit on 
account of faulty reflexes or respiratory failure, which complications may 
eventually cause the death of the patient. 
In order to avoid these complications, at present, the status of the 
neuromuscular block is evaluated by means of stimulation of a peripheral 
motor nerve and measurement of the degree of motility of the muscle 
innervated by said nerve. 
There are various methods and devices designed to stimulate peripheral 
nerves by means of transcutaneous electrodes, for example, the stimulators 
of Neuro Technology, Inc., Houston, Tex., U.S.A. The most important 
problem lies in the evaluation or measurement and monitoring of the 
neuromuscular block and the adequate administration of the muscle relaxant 
drug to maintain the desired level of blockage. At present, the evaluation 
of the block is done by evaluation of the electrical activity, the force 
or the movement of the muscle during its contraction. The methods used up 
to the present date are: 
1) The visual method. One visually evaluates the movement of a muscle after 
the stimulation of the motor nerve which innervates it. The inexactitude 
and difficulty of quantification of the method are obvious, but its 
simplicity makes it the one which is used most frequently today. 
2) The tactile method. Similar to the preceding method, but in this case 
the evaluation is done by means of the perception through the hand of the 
anesthesiologist of the force of contraction of the patient after the 
stimulus. As in the preceding case, it is a subjective and inexact method, 
offering little guarantee of determining the exact degree of neuromuscular 
blockage. 
3) By means of electromyography. This consists in the registration of the 
muscular electrical activity evoked by stimulating the motor nerve which 
innervates said muscle. There are various devices and apparatus on the 
market, which monitor the neuromuscular block by said technique, which is 
described, for example, in U.S. Pat. No. 4,291,705, among others. The 
primary problem which this technique entails is its difficulty of 
application and the sophistication of the equipment, so that it has only 
been used essentially in research, without coming to be used as a 
practical and routine technique. 
4) By means of force transducers. In this case, one registers the force of 
the thumb when the ulnar nerve is stimulated. Again, there are various 
devices on the market, such as the "Relaxograph" of Biometer International 
A/S, Denmark. As in the preceding case, the primary problem consists in 
the complexity of the technique used, which involves having to immobilize 
the arm in order to perform a proper registration. For this reason, and 
the costly equipment, this device is not very practical for routine use. 
5) By means of accelerometry. This method is, after the visual method, the 
most popular one. It is based on placing a biaxial or biaxial 
accelerometric sensor on the thumb which, when the ulnar nerve is 
stimulated, provokes a movement in same, which is picked up by the 
accelerometer. This is a rather valid method, but it still has the 
drawback that several electrodes separate from the sensor have to be put 
in place in order to stimulate the peripheral nerve. On the other hand, 
the accelerometer is fragile and requires a certain immobilization of the 
arm. Other placements of the accelerometer have been described, for 
example, on the face, in which case one must stimulate a motor branch of 
the facial nerve and the stimulus electrodes must arrive separately from 
the accelerometer, increasing the risk of certain of the elements becoming 
detached from the skin. As an example of monitors based on accelerometry, 
one can mention the "Accelograph" and "Tof-Guard" models, both of them 
from Biometer International A/S, Denmark, and that described in U.S. Pat. 
No. 4,817,628, which is another example of a facial accelerometer. 
6) By means of flexible-sheet piezoelectric sensors. The phenomenon of 
piezoelectricity has been known for many years, as has been its 
application in the field of medicine, for example, with the application of 
piezoelectric sensors which, through their deformation, capture the 
plethysmographic wave transmitted to the skin. Based on this principle, 
the monitor of U.S. Pat. No. 5,131,401 requires, like the other methods, 
the stimulation of a peripheral motor nerve, primarily the ulnar nerve, 
and it comprises some cables for the stimulus electrodes and others for a 
sensor in the form of flexible piezoelectric sheets, which are placed on 
the palm of the hand and register the contraction of the muscles of the 
hand. Like the "Tof-Guard" model, it also has a microprocessor which, by 
means of a program, enables a programmed stimulation and visualization of 
the quantified response of the neuromuscular block. 
The primary drawback presented by these monitors, except for the last one, 
is that they require the stimulation of a peripheral motor nerve, 
specifically the ulnar nerve, and the placement of the sensor on the hand 
or thumb. They likewise require the use of two electrodes for separate 
stimulation of the sensor element of the response, which increases the 
risk of a detachment of the electrodes or of the sensor. 
Owing to this, the placement of the electrodes may be awkward and a certain 
immobilization of the limb is necessary, limiting the placement in other 
positions. On the other hand, this type of apparatus might be more 
sensitive to certain interference or involuntary movements of the patient. 
With respect to the control of the neuromuscular block, there are various 
works based on pharmacokinetic models and short-circuit models, such as 
those described in individual articles of medical journals: 
"Quantitative assessment of residual antidepolarizing block (Partil)" Ali 
H. H. et al., Br J Anaesthesia 1971 vol. 43 pp. 473-477. 
"Monitoring of neuromuscular function" Ali H. H. et al., Anesthesiology 
1976 vol. 45 pp. 216-249. 
"A microcomputer based controller for neuromuscular block during surgery" 
Ritchie G. et al. Ann Biomed Eng 1985 vol. 13 pp. 3-15. 
"Microcomputer based muscle relaxation monitor and controller for clinical 
use" Bradlow H. S. et al. Med Biol Eng Comput 1985, vol 23 pp. 547-555. 
"Online parameter estimation and control of D-Tubocurarine-induced muscle 
relaxation." Rametti L. B. et al., Med Biol Eng Comput 1985 vol. 23 pp. 
556-564. 
"Online control of Atracurium induced muscle relaxation" Bradlow H. S. et 
al, J Biomed Eng 1986 vol. 8 pp. 772-775. 
"Computer-Controlled Muscle Paralysis with atracurium in the Sheep" D. G. 
Lampard et al, Anesthesia and Intensive Care, vol. 41 (1986) pp. 316-320. 
"Clinical automatic control of neuromuscular blockade" Asbury A. J. et al, 
Anaesthesia 1986 vol. 41 pp. 316-320. 
"Infusion of vecuronium controlled by a closed-loop system" Br J Anaesth 
1986 vol. 58 pp. 1100-1103. 
"Closed-loop administration of Atracurium" N. R. Webster et al, Anesthesia 
vol. 42 (1987) pp. 1085-1091. 
"A model-based self-adjusting two-phase controller for vecuronium-induced 
muscle relaxation during anaesthesia" Jalkist R. R., IEEE Transac Biomed 
Eng 1987 vol. 34 pp. 583-594. 
"Closed-loop infusion of atracurium with four different anesthetic 
techniques" O'Hara D. A. et al, Anesthesiology 1991 vol 74 pp. 258-263. 
These articles describe instances of control of the muscle relaxation by 
means of computers with pharmacokinetic models, through the previously 
mentioned sensors, or with closed-circuit systems. 
There are correct approximations in all the instances, but even so they are 
still experimental and not very safe models, which owing primarily to 
the-need to stimulate a peripheral nerve are impractical and complicated 
in use, whether because of the type of transducer used or because of the 
pharmacokinetic model, which requires much data entry or very 
sophisticated computers. 
DESCRIPTION OF THE INVENTION 
The aforesaid drawbacks can be eliminated with the method and apparatus of 
the invention. 
The method for monitoring and/or controlling the neuromuscular block which 
is the subject of the invention is characterized by the fact that the 
nerve stimulation is done on the skin covering the muscle or muscles on 
which the detection of the response to said stimulation is performed, that 
is, without having to stimulate any peripheral nerve. 
Thanks to this method, it is not necessary to stimulate the peripheral 
nerve and the stimulator-detector device can be placed on the upper or 
lower limb, depending on the type of surgery being performed, without 
having to confine the stimulation to the ulnar nerve. 
Optionally, the method of the invention also comprises the automatic 
control of the supply of the muscle relaxant drug on the basis of a 
detection of the muscle response. 
The invention also pertains to an apparatus for the monitoring and/or 
controlling of the neuromuscular block, which comprises means for the 
application of the nerve stimulation, means for the detection of the 
response to the stimulation, and means for monitoring the neuromuscular 
block, and it is characterized by the fact that the means for the nerve 
stimulation and the means for the detection of the response are arranged 
in the same body. 
Thanks to this arrangement in a single body, the following advantages are 
achieved: 
i) a single element serves to measure the arterial pressure and to measure 
the neuromuscular block, achieving a more compact and handy device, 
ii) the placement becomes easier, 
iii) the independent disconnection of certain of the components is avoided, 
iv) it simplifies the monitoring in the operating theater. 
According to another embodiment, the apparatus of the invention comprises 
means for the application of the nerve stimulation, means for the 
detection of the response to the stimulation, and means for the monitoring 
of the neuromuscular block, and it is characterized by the fact that it 
also comprises means for supply of the drug which produces the 
neuromuscular block and means of control which coordinate the generation 
of the stimulus, the registration of the activity, the data processing, 
the computation of the drug dosage and the control of the means for supply 
of the drug as a function of the computed dosage. 
The apparatus of the invention thus comprises three essential parts: 
i) means for the nerve stimulation, comprising the stimulator and the 
stimulus electrodes, 
ii) means for the detection of the muscle response, consisting of a sensor, 
which can be of various types, 
iii) means of monitoring and control, which can be of various types, 
depending on the specific embodiment of the invention, and 
iv) optionally, a closed circuit for the automatic dispensing of a drug. 
The apparatus of the second embodiment can also be characterized by the 
fact that the means for the application of the nerve stimulation and the 
means for the detection of the response are arranged in a single body, 
whereby the advantages already described are also obtained in this 
instance. 
Preferably, the apparatus is characterized by the fact that the body is a 
cuff of the type used for the measurement of arterial pressure, provided 
with means for the detection of the pressure or connected to said means, 
whose cuffincorporates means for the application of the nerve stimulation. 
In this way, the electronics and the maneuvers involved in the placement of 
the sensor are simplified, since the same arterial pressure cuff end 
transducer of the noninvasive arterial pressure monitor are used. This 
arrangement makes it possible to simplify the technique for measurement of 
the neuromuscular block. 
Preferably, the means for the application of the nerve stimulation comprise 
at least two electrodes. 
Also preferably, the means for application of the nerve stimulation and the 
means for the detection of the pressure are combined with the means of 
monitoring through a multiconductor tube which contains on the inside an 
air conduit for transmitting the pressure waves and at least one pair of 
electrical conductors for transmission of the stimulation pulses. 
In a preferred embodiment, said conductors are included in the wall of the 
multiconductor tube. 
Due to the fact that there is only a single tube which transmits the 
pressure wave and the contraction wave and which also includes the cables 
with transport the stimulus, the use of the device becomes extremely 
simple. This solution is also more economical, since it makes use of the 
cuff and the electronic circuits of the arterial pressure monitor. The 
electrical system is more simple and less cumbersome. 
The method of the invention also represents a great advance with respect to 
all of the foregoing ones, including the most modern (Tof-Guard and U.S. 
Pat. No. 5,131,401), since it does not require the stimulation of a 
peripheral motor nerve in order to register the muscle activity. The 
method of the invention is based on the stimulation of the intramuscular 
neural pathways and the nerve endings of the muscular motor plate by the 
application of a stimulus current to the skin directly over the muscle 
whose activity one desires to gauge. 
Usually, the stimulus current does not exceed 50 mA and the time of 
application should not be more than 30 ms, in order not to directly 
stimulate the muscle fibers, which would produce a faulty reading of the 
neuromuscular block. 
The means of monitoring can be any of the bloodless arterial pressure 
monitors existing on the market, modified by the incorporation of a pulse 
generator for the muscle stimulation, with the possibility of adjusting 
various parameters, such as the intensity of the stimulus or the time 
between readings, and with the possibility of furnishing on-screen data 
corresponding to the muscle relaxation. 
The monitors can also have LEDs of light and sound alarm signals for cases 
of loss of signal or contact of the electrodes (by impedance), 
disconnection of the sensor or any of its parts, excessively high or low 
level of blockage with respect to the predetermined level, as well as 
other alarms which are common in medical devices, such as current faults, 
loss of power supply, etc. 
The means of monitoring and control comprise an insulated amplifier, with 
filters for 50-60 Hz and high frequency to avoid interference from the 
electrical scalpel, a stimulator circuit of the type commonly used for 
nerve stimulation, capable of generating currents up to an intensity of 
100 mA, a circuit to measure and control the intensity of the stimulus 
current, an air pump to inflate the cuff, and optionally an A/D converter, 
a memory bus and a microprocessor which, by means of a program in EPROM 
memory, controls all the functions of the device, coordinating the 
following closed-circuit cycle: stimulation, registration, data processing 
and signal processing according to standards for assessment of the 
neuromuscular block (evaluation of the TOF).

DESCRIPTION OF A PREFERRED EMBODIMENT 
FIG. 2 shows a conventional placement of the electrodes 1, 2 and the sensor 
3. In this case, the electrodes 1, 2 are arranged on the arm and the 
sensor 3 is arranged on the finger. One can see in the figure the two 
cables 4, 5 corresponding to the electrodes and the cable 6 corresponding 
to the sensor. 
FIG. 3 shows the stimulator-detector device of the apparatus of the 
invention. In the figure, one can see the electrodes 7, 8 arranged in a 
pressure cuff 9. As the large-scale detail shows, the multiconductor tube 
10 comprises an air conduit 11 and two electrical conductors 1 2 and 13. 
In the embodiment shown, the conductors 12 and 13 are included in the wall 
of the multiconductor tube 10. 
FIG. 1 shows a continuous tracing curve A which corresponds to the method 
of the invention with the pressure cuff, provided with the stimulus 
electrodes arranged over the muscle in which the block is being evaluated, 
and a continuous tracing curve B which corresponds to a conventional 
method, with the stimulus electrodes over the ulnar nerve and the sensor 
on the thumb. 
In order to demonstrate the validity of the method of the invention and to 
ensure that the direct cutaneous stimulation over the muscle mass in which 
one wishes to evaluate the neuromuscular block does not produce direct 
stimulation of the muscle fibers, but instead the stimulus follows the 
intramuscular nerve pathways and nerve endings of the muscle motor plate, 
the following test was performed: sensors were placed on the thumb and 
stimulus electrodes over the ulnar nerve, following the instructions of 
the previous conventional methods. Curve B was obtained. 
In the same patient and at the same time, the pressure cuff with the 
electrodes on its inner surface was put in place, following the 
instructions of the method of the invention. Curve A was obtained. 
Comparing the trend of both curves during the application of muscle 
relaxant drugs to anaesthetized patients, results were obtained which 
validate the method of the invention, since curves A and B show a similar 
behavior for the same method of application of the drugs. 
FIG. 4 shows the different components of the apparatus of the invention: 
In the first place, the stimulator-detector device 14 detailed in FIG. 3, 
which includes the stimulus electrodes 7, 8 and the pressure cuff 9. This 
can be made in different sizes, depending on the size of the limb to which 
it is applied, it being possible to have versions for adults and versions 
for children. 
The device can be disposable or reusable, and it comprises the two 
electrodes 7, 8, likewise disposable or reusable, which are coupled to the 
cuff and have a stimulus surface varying between 0.05 cm2 to 5 cm2 for 
each. The electrodes 7, 8 are placed on the inner surface of the arterial 
pressure cuff 9, which, with the muscle contraction wave transmitted to 
the skin, generates a pressure wave proportional to the muscle contraction 
that is transmitted through the tube to the pressure transducer, arranged 
inside a conventional type of arterial pressure monitor 15. 
The stimulation electrodes 7, 8 can be situated in various ways on the 
inner surface of the cuff 9. The more far apart they are, the greater the 
number of nerve endings stimulated and the larger will be the response. 
The cycle used for the measurement is as follows: 
1) Inflate the cuff slightly to ensure good contact between the electrodes 
and the skin (between 10 and 300 mmHg). 
2) Generation and application through cutaneous electrodes of a series of 
four stimuli &lt;50 mA and &lt;30 me in duration at a frequency of 2 Hz, known 
as "TOF" ("Train of Four", the standard accepted in all methods of 
evaluation of the neuromuscular block). 
3) Registration of the pressure generated inside the cuff by the wave which 
is transmitted to the surface of the skin by the contractions of the 
muscle. 
4) Digitization and processing of the signal, graphic representation 
through an LCD or electroluminescent screen. 
FIG. 4 shows one embodiment of the apparatus of the invention. In this 
figure, one can see the stimulator-detector device 14 as represented in 
FIG. 3 and a conventional type of arterial pressure monitor 15. 
In the lower righthand portion of the monitor dial 15 one can see the 
connections 16, 17 and 18, corresponding respectively to the 
multiconductor tube 10, the information on oxygen saturation, and the 
electrocardiogram. 
In the upper righthand portion one can see a pair of control buttons, one 
of which 19 serves to adjust the time between two readings and the other 
20 is used to adjust the intensity of the stimulus. 
On the screen at left there appear two curves, the upper one corresponding 
to the electrocardiogram and the lower one to the pulse signal or 
plethysmogram. The bars in the lower part of the screen represent the 
responses to the muscular stimulation over time. The screen can also 
display data such as the muscular activity (Musc: 30%), heart rate (FC: 
60), arterial pressure (PA: 120/70), and oxygen saturation (Sat: 98%). 
The conventional monitor 15 is provided with a pulse generator for the 
muscle stimulation through the conductors 12, 13 (FIG. 3) and the 
electrodes 7, 8. 
FIG. 5 shows a flow chart of a closed circuit. The electrical stimulator 21 
stimulates the muscle 22. The sensor 23 provides the muscle response to 
the means of control 24. 
A program is used to control the data acquisition, A/D conversion, and 
analysis of the data, furnishing the signals to actuate the system for 
supply or infusion of the muscle relaxant 25. In this way, the infusion 
will be automatic.