1 Department of Anaesthesia and 2 Department of Research, University of Basel/Kantonsspital, CH-4031, Basel, Switzerland. 3 Departments of Surgery and Physiology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 294, Minneapolis, MN 55455, USA
*Corresponding author. E-mail: hfginz{at}aol.com
Accepted for publication: September 4, 2003
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Abstract |
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Methods. Thirty-three healthy patients undergoing anaesthesia for elective lower limb surgery were investigated. Twenty-two patients received a general anaesthetic with either propofol (n=12) or sevoflurane (n=10); for the remaining 11 patients spinal anaesthesia with bupivacaine was used. We used a non-invasive muscle force assessment system before and during anaesthesia to determine the contractile properties of the ankle dorsiflexor muscles after peroneal nerve stimulation (single, double, triple, and quadruple stimulation). We measured peak torques; contraction times; peak rates of torque development and decay; times to peak torque development and decay; half-relaxation times; torque latencies.
Results. Males elicited greater peak torques than females, medians 6.3 vs 4.4 Nm, respectively (P=0.0002, Mann-Whitney rank-sum test). During sevoflurane and propofol anaesthesia, muscle strength did not differ from pre-anaesthetic values. During spinal anaesthesia, torques were diminished for single-pulse stimulation from 3.5 to 2.0 Nm (P=0.002, Wilcoxon signed rank test), and for double-pulse from 7.6 to 5.6 Nm (P=0.02). Peak rates of torque development decreased for single-pulse stimulation from 113 to 53 Nm s1 and for double pulse from 195 to 105 Nm s1. Torque latencies were increased during spinal anaesthesia.
Conclusions. At clinically relevant concentrations, propofol and sevoflurane did not influence involuntary isometric skeletal muscle strength in adults, whereas spinal anaesthesia reduced strength by about 20%. Muscle strength assessment using a device such as described here provided reliable results and should be considered for use in other scientific investigations to identify potential effects of anaesthetic agents.
Br J Anaesth 2004; 92: 36772
Keywords: anaesthetics; muscle, isometric contraction; muscle skeletal; muscle, torque
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Introduction |
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To determine muscle strength, isometric assessment tools have to be distinguished from dynamic tools. The measured values are strongly influenced by an investigators experience and the patients voluntary efforts, so results are not always objective and reproducible.4 To improve objectivity, fixed devices have been developed. By using electrical nerve stimulation and electronic data acquisition, it is now possible to get quantitative, non-invasive muscle force assessment results, independent of a subjects voluntary efforts.58
We used a muscle force assessment system, which was originally developed for neurological trials, to investigate the influence of propofol, sevoflurane, or spinal anaesthesia with bupivacaine on human involuntary isometric skeletal muscle strength following electrical stimulation.
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Methods |
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Patients
All 33 patients gave their written informed consent, and the Human Ethics Committee of the University of Basel, Switzerland approved the experimental protocol. All patients were ASA I and were to undergo orthopaedic or venous surgery to the lower limb. The patients chose whether to receive either spinal anaesthesia or general anaesthesia. Those patients who chose to receive general anaesthesia were allocated randomly to receive either propofol or sevoflurane for induction and maintenance of anaesthesia.
Muscle force assessment system
For nerve stimulation, a Grass S11 stimulator (Grass Medical Instruments, Quincy, MA) was used. A special device that securely held the subjects leg was used for quantification of muscle torque (Fig. 1).58 The torque was measured by a strain gauge (SG-2/350-LY41 Strain Gauges, OMEGA Engineering, Inc., Stamford, CT) attached to an aluminium bar that restrained movement of the footplate. The output of the strain gauge was amplified (amplifier: Grass Medical Instruments); voltage changes proportional to the muscle torque were digitized through a data acquisition card (DAQCardTM-1200, National Instruments, Austin, TX), converted into force and then stored on a personal computer. All data acquisition and analysis programs were written with LabVIEW 2 (National Instruments, Austin, TX).
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After arrival in the operating theatre, an i.v. catheter was sited and an infusion of Ringer lactate solution (500 ml) was started. Standard monitoring was attached and a surface temperature probe was used to determine the temperature over the tibialis anterior muscle (GeniusTM, infrared thermometer, Sherwood-Davis & Geck, Gosport, UK): for patients receiving general anaesthesia, the Bispectral IndexTM was monitored also.
The muscle force assessment system was attached to each patient as follows: the patient was laid on the surgical table with one leg strapped in a stabilizing device that was fitted with a force measuring boot into which the foot was placed. A convective warm-air system was used to minimize variability in dorsiflexor muscle temperature; the skin temperature of the leg was maintained between 31 and 32°C. After cleaning the skin with an alcoholic wipe, a pair of small ball-shaped electrodes was pressed tightly against the skin behind the head of the fibula for transcutaneous common peroneal nerve stimulation. An electromyogram (EMG) of the tibialis anterior muscle was recorded with surface patch electrodes.10
The supramaximal voltage (approximately 5090 V with 0.3 ms duration) was used for stimulation and this was determined by increasing the voltage until no further increases in muscle twitch torque and in the EMG signal of the ankle dorsiflexors were detected. The optimal muscle length for isometric contraction (in this case, the ankle joint position) was determined by moving the torque plate until twitch torques reached a maximum.9 This position of the torque plate was then fixed and kept unchanged during the experiment. Baseline measurements were then performed. The protocol included single, double, triple, and quadruple-pulse peroneal nerve stimulation.58 These were unidirectional depolarizing pulse stimuli with a pulse duration of 0.3 ms. The pulse interval for the multiple pulse stimulations was 5 ms. Between each set of stimuli there was a 2 min rest period. After baseline measurements were finished, general or spinal anaesthesia was administered.
One of two general anaesthetic regimens was used: (i) a target controlled infusion (TCI) of propofol with the target concentration set at 5 µg ml1; (ii) inhalation induction with sevoflurane 68 vol%, in oxygen 100%, followed by maintenance with sevoflurane at an end-tidal concentration of 33.5 vol%. A laryngeal mask was used in both groups for airway maintenance and ventilation of the lungs was controlled to keep the EE'CO2 at 4.55 kPa. After a 20 min stabilization period, the measurements were repeated. During this measurement period, the Bispectral IndexTM was between 40 and 50. In the propofol group, blood was taken and the plasma obtained was used to determine the concentration of propofol by high performance liquid chromatography with fluorescence detection.
Spinal anaesthesia was performed with hyperbaric bupivacaine 0.5%, 0.2 mg kg1. When a stable sensory level was reached (upper level between the 6th and 9th thoracic dermatome), the second set of measurements was performed. Completion of both sets of measurements took about 1 h for each subject.
Data analysis
The following indices of isometric skeletal muscle performance were determined: (i) peak torque (Nm): the maximum amount of developed involuntary isometric muscle torque; (ii) contraction time (ms): time from the onset of torque development to peak torque; (iii) half-relaxation time (ms): time for the torque to decay from its peak to 50% of peak torque; (iv) peak rate of torque development (Nm s1): the maximum rate (first derivative) of torque development; (v) peak rate of torque decay (Nm s1): the maximum rate of torque decay; (vi) time to peak torque development (ms): the time from the onset of torque development to the peak rate of torque development; (vii) time to peak torque decay (ms): the time from the peak rate of torque development to the peak rate of torque decay; (viii) torque latency (ms): the time from the stimulus to the onset of torque development (Fig. 2).
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Results |
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During spinal anaesthesia, peak torque values were diminished for single- and double-pulse stimulation but not for the other stimulation modalities (Table 2). The peak rates of torque development decreased for single- and double-pulse stimulation and the torque latency period for single-pulse stimulation only was increased (Table 2).
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Discussion |
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Propofol blocks voltage-gated channels and thus has a neuromuscular blocking agent effect. This occurs especially in pathological conditions that result in a higher fraction of inactivated channels, such as hypoxia, myotonia, or ischaemia.11 12 Thus, propofol might be the drug of choice for induction of anaesthesia in patients with myotonia. Propofol also exerts a direct negative inotropic effect on failing and non-failing human myocardium, although only at concentrations exceeding the clinical-dose range.13
Volatile anaesthetics inhibit skeletal muscle sodium channels. Mountsey and colleagues describe a dose-dependent enhancement of the rate of sodium current decay and a small reduction in sodium current amplitude in rat skeletal muscle for halothane.1 In animals, the compound muscle action potentials are significantly lower during application of volatile anaesthetics.14 15 Bouhemad and colleagues describe a moderate negative inotropic effect in rat diaphragm muscle in vitro during application of isoflurane (at 2x MAC).16 In an in vitro study using animal tissue, sevoflurane did not enhance the reduction of tension induced by diaphragmatic fatigue but enhanced the prolongation of contraction time and half-relaxation time.17 Halothane causes a decreased calcium sensitivity and decreased isometric tension in human type I, but not type II skeletal muscle fibres.18 On the other hand, there is an increased maximal skeletal muscle Ca2+-activated force in the presence of volatile anaesthetics.19 Moreover, volatile anaesthetics have a direct action on neuromuscular transmission.3 20 Thus, the effects on striated muscles remain controversial.
We found no influences of sevoflurane or propofol on human isometric skeletal muscle strength in vivo. The short-term effect-site equilibration time of propofol and its high drug transfer rate to the peripheral compartment enable us to assume that propofol concentrations in skeletal muscle and plasma were similar. The plasma concentration of propofol was in the range of the half-maximum blocking concentration of skeletal muscle sodium channels; thus, the effects were too small to be measured in our clinical setting.11 21
Since volatile agents reduce isometric force values by about 10% of baseline values in vitro,16 their effects again could have been too small to be measured in vivo. Moreover effects of volatile agents are supposed to be more pronounced during muscle fatigue.17 The distribution of muscle fibre types with their different susceptibility towards volatile anaesthetics can also vary between subjects.22
Spinal anaesthesia blocks the roots of the nerve fibres and the superficial layers of the spinal cord.23 This results in a flaccid paralysis of the muscles and block of the sympathetic outflow. Whereas the main part of this central sympathetic outflow innervates organs such as the heart, lungs, sweat glands, and skin, only a minor component reaches the skeletal muscle and has no measurable influence on muscle tone, as was demonstrated by Smith during spinal anaesthesia.24 Moreover, during static exercise in humans, central command was found to contribute very little to the activation of sympathetic outflow in skeletal muscle.25 However, peripheral afferent impulses from muscle mechanoreceptors (muscle spindles), Golgi tendon organs, and chemosensitive endings in muscles influence sympathetic nerve activity and skeletal muscle tension by reflex mechanisms. During static handgrip, an increased sympathetic discharge to muscle was measured, and muscle sympathetic nerve activity returned to control values during relaxation.26 27 Electrically evoked involuntary biceps flexion also results in increased muscle sympathetic nerve activity.26 During spinal anaesthesia, these afferent impulses are blocked, which could explain the lower values for evoked torque and peak rate development. Direct actions of local anaesthetics on the pre-synaptic, post-junctional, and muscle membranes are only relevant for i.v. application with a moderate to high drug-plasma level and not for spinal application, thus excluding this effect from contributing to our findings.28
The following points must be considered when assessing the relevance of our results. First, for a complete assessment of muscle function it is desirable to study strength variables on the load continuum from isotonic (with low loads) to isometric (with high loads) conditions. In our setting, only isometric measurements were performed. However, negative inotropic effects of anaesthetics typically are found under isometric and not isotonic conditions.16 Secondly, completely standardized conditions are only possible in in vitro studies; for example, inter-subject variability in perfusion, tissue temperature, and muscle cross-sectional area may have influenced the test results. However, clinical trials are required to confirm in vitro results under clinical conditions and such variability can be minimized using appropriate study groups.
Our study is the first to use the described muscle-force assessment system during anaesthesia. This new system made it possible to obtain objective and reliable results, independent of a subjects voluntary effort.58 The system is versatile, enabling the examination of different muscle groups.7 Thus, we recommend such a system to investigate skeletal muscle strength, for example, in patients with potential muscle atrophy, critical illness polyneuropathy, or myopathy.
In conclusion, we evaluated the isometric skeletal muscle strength of the lower leg under different anaesthetic regimens in humans. At clinically relevant concentrations, neither sevoflurane nor propofol changed muscle strength, whereas during spinal anaesthesia there was a small impairment of strength. The skeletal neuromuscular blocking agent properties of anaesthetics do not seem to have a profound effect on isometric skeletal muscle strength in humans in vivo.
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Acknowledgement |
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