Neuromuscular Blockers

Introduction

Muscle relaxation is part of a balanced anaesthetic technique. Most anaesthetic agents produce a mild-moderate amount of muscle relaxation and often this is not sufficient. Increased muscle relaxation can be produced by increasing anaesthetic depth, the use of local anaesthetic techniques, or the use of centrally or peripherally acting muscle relaxants. However, it is important to realise that muscle relaxants have no anaesthetic or analgesic effect themselves and so should never be used alone.

Neuromuscular blocking agents(NMBA) are peripherally acting muscle relaxants. They can be classified as depolarising or non-depolarising depending on whether they are competitive or not.

Neuromuscular Transmission

To understand tranmission of an action potential at the neuromuscular junction it is important to understand the anatomy of the junction. At the nerve terminal, there are a huge number of vesicles containing acetylcholine (ACh), a neurotransmitter. On the muscle membrane there are a number of nicotinic ACh recpetors. As an action potential reaches the nerve terminal, the ACh contain vesicles fuse with the prejunctional membrane releasing it into the junctional cleft. They diffuse across the cleft and bind to the post-junctional receptors. After binding of two ACh molecules to the two binding sites on the repector the activation of ion channel opening leading to an end-plate potential. If enough channels open, the muscle membrane depolarises and an action potential is generated. This causes release of calcuim ions from the sarcoplasmic reticulum leading to muscle contraction. Binding of ACh is extremely short before it is released and hydrolysed, causing the end of the action potential and muscle contraction. If only one of the two sites is occupied, then ion channel opening does not occur and no action potential is produced.

Monitoring after NMBA Administration

NMBAs act on all skeletal muscles, which includes respiratory muscles. This means that it is essential to have facilities to provide controlled ventilation. Muscles have different sensitivities for NMBAs, with the diaphragm being particularly resistant making it the last to be paralysed and the first to recover. However, laryngeal tissues appear to be relatively sensitive, meaning it may take longer for these tissues to recover after administation. This makes patients at risk of upper airway obstruction after the endotracheal tube has been removed.

Peripheral nerve stimulators are commonly used to assess the muscle relaxation. These devices supply a small electrical current through electrodes, which have been attached to the skin above a peripheral nerve. If the muscle is still under blockade then there is no response to the current, whereas if the blockade is no longer present a muscle twitch is produced. The electrodes can be placed directly onto the skin or via subcutaneous needles. Commonly used sites include the ulnar, peroneal or facial nerve. The most common stimulation pattern used is the train-of-four. This technique involves the delivery of 4 pulses over a 2 second period. If there is non blockade then 4 twitches are observed of equal strength. If a non-depolarising agent has been administered, the twitches become gradually weaker until they disappear. If a depolarising agents has been administered, then the twitches are absent.

The administration of muscle relaxants also makes monitoring anaesthesia difficult as many of the parameters used are affected by the muscle relaxant. For example, eye position often remains central in patients that have received NMBAs. Similarly the palpebral reflex is commonly used to assess anaesthetic depth but in patients that have received NMBAs this reflex is absent. Therefore the following can still be used to asses anaesthetic depth -

• Pulse rate
• Blood pressure
• Salivation and lacrimation
• End-tidal carbon dioxide
• Muscle twitching

Indications for Use

• Deep dissection during surgery.
• Thoracic Surgery
• Replacement of dislocations and fractures.
• Intraocular procedures.

Drugs in this Class

• Depolarising Agents
  • Suxamethonium

• Non-Depolarising Agents
  • Atracrium
  • Cis-atracurium
  • Mivacurium
  • Vecuronium
  • Pancuronium