What Was The First Muscle Relaxant Used In Surgery?

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INTRODUCTION

Neuromuscular Blockade is widely used in medical practice in the operating room and outside. Different uses have been established for this type of drug due to its remarkable ability to facilitate airway management, control alveolar ventilation, abolish motor reflexes and provide skeletal muscle relaxation for various surgical procedures. Its usefulness in the intensive care unit is essential for managing critically ill patients who need better management of ventilatory compliance when sedation and analgesia are insufficient.

NEUROMUSCULAR TRANSMISSION BLOCK

There are three nicotinic receptors at the neuromuscular junction, two located on the muscle surface and one at the parasympathetic nerve.

Upon the arrival of the nerve impulse, acetylcholine molecules are released from the presynaptic nerve ending, cross the synaptic space and stimulate the postsynaptic receptors, allowing the flow of ions through them, depolarising the terminal plate. It is hydrolysed by the enzyme acetylcholinesterase.

The postsynaptic receptors are located just opposite where the acetylcholine molecules are released. An acetylcholine molecule occupies these two receptors ay when two molecules of acetylcholine simultaneously stimulate the two alpha units, a channel opens in the receptor allowing the passage of sodium and calcium into the myocyte and potassium out; it has been estimated that 400,000 receptors open to create enough stimulus to create the potential that triggers muscle contraction.

Depolarising drugs occupy the two alpha subunits just like acetylcholine, so they initially stimulate sodium and calcium channels, producing contractions known as fasciculations, but since these drugs are not affected by acetylcholinesterase, they occupy these subunits for much longer, causing depolarisation and then neuromuscular Blockade.

Non-depolarizing drugs compete with acetylcholine to occupy at least one alpha subunit, competitive inhibition, which causes the ion channel to not open, the membrane will not depolarise, and the muscle will remain flaccid.

There are two classes of muscle relaxant agents as described above:

-Depolarizing.

-Non-depolarizing.

Depolarising drugs

Succinylcholine is the only non-depolarizing drug available, and it has a structure similar to that of two molecules of acetylcholine. The onset of action of this drug is fast, about 1 minute and its duration are short, 17 to 8 minutes; due to the characteristics of succinylcholine, it is used for rapid tracheal intubation, which is essential if you want to reduce the risk of gastric aspiration. Side effects are clinically significant, including muscle pain, hyperkalemia, and increased intraocular and intragastric pressure. Malignant hyperthermia, a rare but potentially fatal hereditary disorder, has been associated with the use of this drug, with an estimated incidence of 1 in 50,000 adults. Hypermetabolic crisis can be controlled with Dantrolene infusion, which showed a reduction of less than 10% in mortality. A mutation in the ryanodine receptor gene, responsible for maintaining calcium flow in skeletal muscle, is attributed as the cause of this disorder. 

Non-Depolarizing Drugs

These drugs were developed in 1942. They are compounds derived from quaternary ammonium and have at least one positively charged nitrogen atom in their molecule structure.

They can be divided into:

-Benzylisoquinolines: D-tubocurarine, Metocurine, Alcuronium, Atracurium, Doxacurium, Mivacurium, and Cisatracurium.

-Quaternary Amines: Galamin

-Amino steroids: Pancuronium, Pipecuronium, Vecuronium and Rocuronium.

Due to their mechanism of action, these drugs do not have the same side effects as succinylcholine, so their impact of action is slower, and they last longer, which makes them more suitable for use in procedures that require prolonged use of muscle relaxation, such as protracted surgeries.

Pharmacodynamics

The clinical pharmacodynamics of these drugs is determined by measuring the speed of action of neuromuscular Blockade and its duration. This is calculated by monitoring the abductor pollicis muscle. The electrical stimulus should be monophasic and rectangular with an optimal time of 0.2 to 0.3 ms.

INDICATIONS FOR THE USE OF MUSCLE

RELAXANTS Endotracheal intubation

Succinylcholine has a very rapid onset of action, but its use is limited only to intubation of patients with gastric residuals. Otherwise, non-depolarizing drugs are used, although their slow motion makes the anaesthetists gradually control ventilation until the Blockade is maximum. The non-depolarizing muscle relaxant most similar to succinylcholine concerning its action time is rocuronium, although its duration is identical to that of vecuronium.

Short surgical procedures

Before the appearance of atracurium, cisatracurium and vecuronium, surgical procedures of less than 30 minutes were demanding from the point of view of relaxation, and this defect was corrected by administering smaller doses of D-tubocurarine so that the duration of its action is minor, but delayed the onset of action of this drug. Another alternative was to administer succinylcholine boluses repeatedly, which resulted in variations in the degree of Blockade and increased the risk of side effects. The introduction of mivacurium has proven to be helpful in this respect. The onset of action is similar to that of atracurium, but its recovery is two to three times faster.

Long surgical procedures Long

-acting non-depolarizing drugs such as d-tubocurarine, pancuronium, pipecuronium, and doxacuronium are most effective in procedures lasting more than 90 minutes. However, repeated doses of these drugs are sometimes required in courses lasting several minutes. Hours.

A more satisfactory alternative may be the administration of short-acting relaxants such as atracurium or its isomer in a continuous infusion, using drugs with anticholinesterase effect once the injection is stopped. Neuromuscular monitoring is recommended in this type of procedure.

In Intensive Care Units

They are occasionally used in addition to analgesics and sedatives to maintain adequate oxygenation in patients undergoing mechanical ventilation. These drugs are essential in managing patients with adult respiratory distress syndrome.In the past, repeated doses of agents such as pancuronium were used, and the drug cost was low. Still, in patients with organ failure, recovery from neuromuscular Blockade was slow, which delayed the process of weaning and disconnection from the mechanical ventilator. A similar effect occurred with vecuronium due to the accumulation of 3-desacetylvecuronium, its active metabolite.

Atracurium and its isomer have proven to help manage critically ill patients. No evidence has been found that demonstrates a delay in recovery when administered by continuous infusion, even for days. What makes this technique ineffective is the high cost of the injections. Drugs compared to pancuronium boluses added to the potential side effect of laudanosine. Studies on cisatracurium in critical patients report that the recovery rate is almost identical to that of atracurium with much lower plasma laudanosine concentrations.

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