Neuromuscular Relaxants

Endotracheal Intubation in E.R. and O.R.Immobility at subconscious level.Better surgical conditions of access.

0. Why do we need Relaxants?

Motor Neurons’ Pathway.

The motor system consists of

the pyramidal and

extrapyramidal system.

CorticoSpinal, CorticoNuclear

and CorticoBulbar tracts all

arise from the motor cortex and

pass to muscle fibers in the

extremities, face and eye. The

corticospinal tract start in the

motor center of the cerebral

cortex. The motor impulses

originates in the Giant

pyramidal cells or Betz cells of

the motor area, precentral

gyrus, of cerebral cortex. These

are the upper motor neurons

(UMN) of the corticospinal

tract. The axons of these cells

pass in the depth of the

cerebral cortex to the Corona

radiata and then to the Internal

Capsule passing through the

posterior branch of internal

capsule and continue to

descend in the Midbrain and

the Medulla Oblongata. In the

lower part of Medulla oblongata

80 to 85% of these fibers

decussate (pass to the opposite

side) and descend in the White

Matter of the Lateral funiculus

of the spinal cord on the

opposite side.

Frontal lobe to Area 4 and 6.Nerves pass through the Pyramidal and the extra- tracts.Exit via the spinal nerves till reaching the MEP.Action Potential triggers ACh. Release.ACh. Binding & Ligand-Gated Na+ Channels

open.EPPs till full blown AP.T-Tubule Propagation and contraction.ACh. Hyhdrolysis by “true” AcetylCholine Estrase.

RAPID

I. Physiology

Nerve synapses on muscle, SEM

Coloured scanning

electron micrograph

(SEM) of the junctions

between a nerve cell

(green) and a muscle fibre

(red). The nerve cell

(motor neuron) ends in a

group of pads called end

plates. The end plate holds

neurotransmitter

chemicals. When

activated, the end plate

releases a

neurotransmitter, which is

taken up by receptors on

the muscle's side of the

synapse. This makes the

muscle contract. In

neuromuscular synapses

such as this, the

neurotransmitter is the

chemical acetylcholine.

Either intervening at level of Motor Cortex and RAS.

Or at Local Nerve Block.Or at Motor End Plate.

Physiologically similar to ACh; Depolarising MRs.

Morphologically similar to ACh; Non-Depolarising MRs.

II. Grand Scheme

III. Depolarising M.R. – Succinyl Choline (sux)

Given as an I.V., circulating in Blood.SUX. Binding & Ligand-Gated Na+

Channels open.EPPs till full blown AP.T-Tubule Propagation and contraction

= Fasiculations.SUX. Hyhdrolysis by “Butyryl” Plasma

AcetylCholine Estrase.

SLOW

IIIa. Mechanism of Action

It remains attached to the receptors for MINUTES, during which the Ligand-Gated Na+ Channels remain opened. Na+ enters and K+ exits.

Since Ca+2 kinematics are independent of membrane polarity, It re-enters the Sarcoplasmic Reticulum, hence muscle flaccidity.

Thus muscle remains depolarized and flaccid. This is termed Phase I Block, and it’s entirely SUX-dependant. That is, reversible upon SUX removal.

If Phase I block was maintained via continuous IV Infusion, Insensitivity of the Nicotinic receptors to normal A.Ch. develops and persists even after SUX. Washout. This is termed Phase II Block.

Thus Phase II block resembles the competitive inhibition of A.Ch. exerted by Non-Depolarising MR.

IIIb. Indications

The Only MR having VERY rapid onset at 60 seconds, and VERY short

duration of 5~10 minutes.

Thus indicated in situations needing rapid onset and/or short duration of

Relaxation.

Suxamethonium does not produce unconsciousness or anesthesia, and its effects may cause considerable psychological distress while simultaneously making it impossible for a

patient to communicate. For these reasons, administration of the drug to a conscious patient is strongly contraindicated, except in necessary

emergency situations, where awareness in diminished.

Tracheal Intubation, especially in E.R. and if expected difficult intubation.

Short procedures necessiating relaxation; as Oesopho-, Gastro- and Bronchoscopes.

A premedication in ECT. (Short duration)

Can be used in Second Stage of delivery.

To alleviate severe laryngospasm.

Myotonia Congenita, a Channelopathy; hereditary disease that is caused by mutations in the chloride, sodium or potassium ion transport channels in the muscle membrane, leading to difficulty in relaxing the muscle, or Myotonia.

Myotonica Dystrophia. (Myotonia associated with severe wasting of the muscles)

IIIc. Contraindications

Patients with Congenital or Idiosyncratic properties;

Patients with burns or neuromuscular disorders, as this predisposes to severe Hyperkalimia, up to cardaic arrest.

Patients having previous history of Anaphylaxis following SUX administration.

Patients having previous history of Malignant Hyperthermia following SUX administration.

Patients having previous history of Prolonged apnea following SUX administration. This indicates weak or absent activity of ButyrylCholineEstrase.

MUSCLE FASICULATIONS, that can surmount in acute Rhabdomyolysis.

Post-operative muscle pains.CARDIOVASCULAR; +ABP, -HR, and even

asystole. Latter can also be caused by Hyperkalimia.

OCCULAR; +IOP, practically dangerous if asscociated with ocular traumas. (which is a probability considering its use in E.R. for ETT)

ABDOMINAL; +Intragastric pressure due to Fasiculation of Abdominal muscles.

IIId. Complications

CRANIAL; Hyper-metabolism due to fasciculations produces +PaCO2 , thus increased Blood flow and +ICP.

HYPERKALIMIA. Mainly due to continuous opening of Na+ channels, thus Its massive Influx is electrically equated with a massive K+ efflux.Exaggerated in Burns and Neuromuscular disorders.

MALIGNANT HYPERTHERMIA. Has an AD susceptibility determination. Can occur with other gas anesthetics too.

PROLONGED APNEA following SUX administration. Usually means weak or absent activity of ButyrylCholineEstrase.Since this enzyme is produced by the liver,

Hepatic disorders (cirrhosis), and malnutrition can lead to a decrease in its activity.

Can also occur with Phase II Block.ANAPHYLAXIS; with massive Histamine

release.

Pretreatment of the patient with a small dose Non-Depolarising MR can attenuate many of the side

effects mentioned above.

The recent arrival of the cyclodextrin SUGAMMADEX may

well render suxamethonium obsolete. Sugammadex can be used to 'instantly' reverse the effects of

longer-acting muscle relaxants, particularly rocuronium. This means

that rocuronium can be given in sufficiently high dose to work

quickly, and then reliably reversed when necessary, all without the

unwelcome side effects of suxamethonium.

Thank You

Clinical Uses of MRs

Following Induction of Anaesthesia and administrating the MR, Ventilation continues via face mask, and Intubation can be done upon relaxation of the muscles.

Cough. Hiccough and abdominal wall tightening are all signs of inadequate dose of the relaxant.

They should be differentiated from signs of inadequate dose of the anaesthetic, such as limb movement in response to surgical stimulation.

Rapid Tracheal Intubation; Suxamethonium or Rocuronium.

Haemodynamic Instability; Vecuronium.Renal and Hepatic Dysfunction; Atracurium.In Myasthenia Gravis; AVOID MR; but if

essential, use 1/10 the dose of Atracurium, and titrate.

In Asthmatics; AVOID Histamine releasing drugs.

Choice of the MR.

Normal Tidal volume.Maintain open eyes.Sustain tongue protrusion.Maintain head lift for 5 seconds.Maintain firm hand grip.Effective Coughing.Return of full muscle activity by nerve

stimulators.

Clinical Criteria of Adequate MR Recovery

Shallow respiration and Cyanosis.Jerky movement of extremities.Restless patient.Diplopia.Inability to raise head or extrude tongue.By nerve stimulators.

Clinical Signs of Incomplete MR Recovery

Depolarizing vs. Non- Depolarizing MR

Depolarising Non - Depolarising

Onset Rapid Slow

Duration Short Long

Fasiculations Yes No

Use of AntiCholineEstrase

Increase Block Reverse Block

Antidote No Yes

Effect of repeated use

Phase II Block No

Nerve Stimulators

Special features Different features

Thank You