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  4. Use of neuromuscular blocking agents for surgical or prolonged procedures

Use of neuromuscular blocking agents for surgical or prolonged procedures

Introduction

Neuromuscular blocking (NMB) drugs, or “muscle relaxants” produce paralysis of the skeletal muscles. They may be used either to aid stable mechanical ventilation by blocking spontaneous respiratory movements or, more frequently, to provide more suitable conditions for surgery. If skeletal muscle tone is eliminated by using a NMB agent, exposure of the surgical site can be achieved more easily and with less trauma to the surrounding tissues. NMB drugs are also used in neurophysiological and other studies, to enable very light planes of anaesthesia to be maintained. Under these conditions, if an NMB had not been administered, spontaneous muscle movements could occur which would interfere with data collection.


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NMB agents must be used with great care, since their administration prevents all movements in response to pain. It would be possible, but obviously inhumane, to carry out a surgical procedure on an animal which had been paralysed but was still fully conscious. This is a recognised clinical problem in people, and it is for this reason that the use of NMB drugs in experimental animals is subjected to careful control in many countries, for example special permission is required to use these agents in the UK, and Institutional Animal Care and Use Committee review is required in the USA. NMB agents are nevertheless extremely useful adjuncts to anaesthesia and enable, for example the use of balanced anaesthetic regimens such as an opioid, an hypnotic and a muscle relaxant to provide stable surgical anaesthesia. 

Monitoring anaesthetic depth with NMBs

If NMB drugs are used, other methods of assessing the depth of anaesthesia must be adopted. As a preliminary step, the proposed anaesthetic technique, excluding the NMB drug, should be administered to an animal of the same species and the proposed surgical procedure carried out. This will establish that the degree of analgesia and unconsciousness will be sufficient to allow surgery to be carried out humanely. Since considerable individual variation in response to anaesthesia occurs and some inadvertent alteration in the technique can arise, for example due to equipment malfunction, it is also necessary to provide an independent assessment of the depth of anaesthesia. Several indicators of anaesthetic depth are of use. Despite muscle paralysis, twitching of muscles may occur in response to a major surgical stimulus and this indicates that the depth of anaesthesia is inadequate. In humans, pupillary size may alter in response to surgical stimulation, but this sign is of little value in most animals, particularly if atropine has been included in the pre-anaesthetic medication.

Changes in blood pressure and heart rate are the most widely used indicators of adequacy of the depth of anaesthesia when using neuromuscular blocking agents. Dramatic changes in heart rate or blood pressure are believed to indicate a depth of anaesthesia insufficient for the surgical procedures that are being undertaken. It has been suggested that increases in heart rate and blood pressure by 10–20% indicate the need for additional anaesthesia. However, many anaesthetics do not block these autonomic responses and 10–20% increases in heart rate can be seen in animals that have not received NMB drugs, and yet these animals show no movement in association with the stimulus. If inadequately anaesthetized, most animals respond to surgical stimuli with a rise in blood pressure, but some animals may show a fall in pressure. So despite their widespread acceptance, these parameters may not always be reliable indicators of adequate anaesthesia.

An alternative method of monitoring the depth of anaesthesia is to use the EEG. Although this requires specialist equipment and expert interpretation, these may be available, especially if neurosurgical or neurophysiological studies are being carried out. Simple changes in the unprocessed EEG, such as onset of burst suppression, can be useful when using some anaesthetic agents, for example halothane. Various derived measures, for example total power and spectral edge frequency have also been used to assess depth of anaesthesia; however, these measures generally cannot be used easily with balanced anaesthetic techniques which involve simultaneous use of hypnotics and analgesics. These same difficulties occur in human subjects, and great efforts have been made to develop monitoring devices that can measure loss of consciousness. The most recently developed have been bispectral index (BIS) monitors, and these are now widely used in human patients, particularly in North America. Initial studies suggest that these and similar indices may also be of value in some species but results may vary. The attraction of the BIS monitor is that it provides a single number as an index of consciousness, or depth of anaesthesia. The disadvantage is that, like the EEG from which it is derived, it is primarily intended to assess the degree of loss of consciousness, and is most predictive when a single anaesthetic agent is used. It is less reliable when using balanced anaesthesia. A further drawback is that it is designed for use in human beings, and the mathematical processing used to create the ‘index’ has been derived from measures made in large numbers of human subjects. Despite these problems, BIS monitors may be of use, particularly for long-term anaesthetic procedures with neuromuscular blockade, but extensive validation for each specific protocol will be needed before these monitors can be relied upon. It is also apparent that BIS values may vary between species at equivalent anaesthetic depths. Given the difficulties of monitoring the level of consciousness in paralysed animals, a more simple approach is to allow the action of the muscle relaxant to subside periodically. The animal will then be capable of responding to painful stimuli with voluntary movements.

Allowing the actions of the muscle relaxant to subside will not always be practicable, especially during prolonged neurophysiological studies, however it is almost always feasible to delay administration of the relaxant until after the start of the surgical procedure. This allows an initial assessment of the adequacy of the depth of anaesthesia to be obtained. It also avoids difficulties in interpreting changes in heart rate and blood pressure that can occur as a side-effect of administration of some muscle relaxants; but this approach does not take account of our current poor knowledge of indicators of consciousness in animals. A more conservative approach is recommended by most regulatory authorities, scientific journals and is adopted at the author’s own institution. Before using neuromuscular blocking agents, it is always advisable to consult an experienced veterinary anaesthetist.

Monitoring the degree of neuromuscular blockade

The degree of neuromuscular blockade can be monitored using a peripheral nerve stimulator. This device delivers a small electrical stimulus, either using skin electrodes or needle electrodes, to a peripheral nerve supplying muscle. In a non-paralysed animal the stimulation causes a muscle twitch. In larger species, the medial aspect of the elbow can be used, or the medial carpal region. Full details of these techniques can be found in a number of veterinary anaesthesia texts.

Selecting neuromuscular blocking agents

The NMB drugs in common clinical use are classified as either depolarizing or non-depolarizing agents. Depolarizing agents, such as suxamethonium, act similarly to the normal transmitter at the neuromuscular junction, acetylcholine. They bind to muscle receptors and trigger a muscle contraction but then produce a persistent depolarization, so preventing further muscle contractions. When drugs that act in this way are administered to an animal, generalized disorganized muscle twitches (fasciculations) are produced before complete skeletal muscle paralysis.

Non-depolarizing, or competitive blocking agents do not cause a muscle contraction before producing paralysis. Drugs in this group include pancuronium, atracurium and vecuronium.

Table: Dose Rates for Neuromuscular Blocking Agents (mg/kg, by Intravenous Injection)
Muscle relaxantMouseRatGuinea pigRabbitCatDogSheepGoatPigNon-human primate
Alcuronium0.1 – 0.20.10.10.25
Atracurium0.20.50.50.3 – 0.6
Gallamine10.1 – 0.2111142
Pancuronium20.060.10.060.060.060.060.060.08 – 0.1
Suxamethonium0.50.20.40.022
Tubocurarine10.40.1 – 0.20.40.40.40.40.3
Vecuronium10.10.10.050.150.150.04 – 0.06

Since these agents act by competing with acetylcholine for receptor sites at the neuromuscular junction, their action can be reversed by increasing the local concentration of acetylcholine. This can be achieved by administering drugs such as neostigmine that block the activity of the enzymes which normally break down acetylcholine. As an alternative, steroid neuromuscular blocking agents (eg rocuronium and vecuronium) can be reversed using sugammadex, and agent that selectively binds to the NMB drug and prevents it acting on the neuromuscular junction. 

Next Article : An introduction to post-operative and post-anaesthetic care after surgical or prolonged procedures

Updated on 12th May 2020

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