Composition:
Each ampoule (2ml) contains 100mg Suxamethonium chloride (50mg/ml).
Mechanism of action:
Suxamethonium is an ultra-short acting, depolarising, neuromuscular blocking agent.
Suxamethonium, an analogue of acetylcholine, inhibits neuromuscular transmission by depolarising the motor end plates in skeletal muscle. The depolarisation may be observed as fasciculation. Subsequent neuromuscular transmission is inhibited as long as an adequate concentration of Suxamethonium remains at the receptor site. Onset of flaccid paralysis occurs within 30-60 seconds of intravenous injection and with single administration persists for 2-6 minutes.
The paralysis following administration of suxamethonium is progressive, with differing sensitivities of different muscles. This initially involves consecutively the levator muscles of the face, muscles of the glottis and finally the intercostals and the diaphragm and all other skeletal muscles.
The short duration of Suxamethonium is considered to be due to its rapid metabolism in the blood. Suxamethonium is rapidly hydrolysed by plasma cholinesterase to succinylcholine (which possesses clinically insignificant depolarising muscle relaxant properties) and then more slowly to succinic acid and choline.
Pharmacokinetic properties:
Absorption: Following intravenous administration, there is rapid hydrolysis by pseudocholinesterase with the initial metabolite being succinylmonocholine a weak neuro-muscular drug.
Distribution: Only a small fraction of suxamethonium reaches the neuromuscular junction. Its action is terminated by diffusion away from the end plate. Succinylcholine does not readily cross the placenta.
Elimination: Succinylmonocholine is metabolised to succinic acid with only a small amount excreted in the urine. And elimination half-life 16.6 ± 4.8 and 11.7 ± 4.5 seconds.
Indications:
It is used in anesthesia as a skeletal muscle relaxant to facilitate tracheal intubation and mechanical ventilation surgical procedures.
Suxamethonium chloride injection is also used to reduce the intensity of muscular contractions associated with pharmacologically or electrically-induced convulsions.
Contraindications:
Hypersensitivity to suxamethonium, or to any of the excipients.
Suxamethonium has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised.
Suxamethonium is recognised as a potential triggering agent in individuals susceptible to malignant hyperthermia and therefore the use of Suxamethonium is contraindicated in patients with a personal or family history of this condition. If this condition occurs unexpectedly, all anaesthetic agents known to be associated with its development (including suxamethonium) must be immediately discontinued, and full supportive measures must be immediately instituted, intravenous dantrolene sodium is the primary specific therapeutic drug and is recommended as soon as possible after the diagnosis is made.
Suxamethonium should not be used in patients with a history of previous prolonged apnoea after suxamethonium or in those with atypical plasma cholinesterase.
Prolonged and intensified neuromuscular blockade following a Suxamethonium, may occur secondary to reduced plasma cholinesterase in the following states or pathological conditions; end stage hepatic failure, acute or chronic renal failure.
An acute transient rise in serum potassium often occurs following the administration of suxamethonium in normal individuals; the magnitude of this rise is of the order of 0.5mmol/litre. In certain pathological states or conditions, the magnitude of the increase in serum potassium following suxamethonium administration may be excessive and cause serious cardiac arrhythmias and cardiac arrest. For this reason the use of suxamethonium is contra-indicated in:
- In patients recovering from major trauma or severe burns; the period of the greatest risk of hyperkalaemia is from 5 to 70 days after the injury and may be further prolonged if there is delayed healing due to persistent infection.
- In patients with neurological deficits involving spinal cord injury, peripheral nerve injury, acute major muscle wasting (upper and/or lower motor neurone lesions); the potential for potassium release occurs within the first six months after the acute onset of the neurological deficit and correlates with the degree and extent of muscle paralysis. Patients who have been immobilised for prolonged periods of time may also be at similar risk.
- In any Patient with pre-existing hyperkalaemia. In the absence of hyperkalaemia and neuropathy, renal failure is not a contraindication to the administration of a normal single dose of suxamethonium, but multiple or large doses may cause clinically significant rises in serum potassium and should not be used.
Suxamethonium causes a significant transient rise in intraocular pressure and should therefore not be used in the presence of open eye injuries or where an increase in intra-ocular pressure is undesirable unless the expected benefit of its use outweighs the potential risk to the eye.
Suxamethonium should be avoided in patients with a personal or family history of congenital myotonic diseases such as myotonia congenita and dystrophia myotonica since its administration may on occasion be associated with severe myotonic spasms and rigidity.
Suxamethonium should not be used in patients with skeletal muscle myopathies e.g. Duchenne muscular dystrophy since its administration may be associated with malignant hyperthermia, ventricular dysrhythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalaemia.
Since the action of suxamethonium may be prolonged in patients known to have inherited atypical plasma cholinesterase, Suxamethonium should not be used in this group unless the expected benefit of its use outweighs the risk.
Posology and method of administration:
Adults:
- The dose is dependent on body weight, the degree of muscular relaxation required, the route of administration, and the response of individual patients.
- To achieve endotracheal intubation, Suxamethonium is usually administered intravenously in a dose of 1mg/kg.
- This dose will usually produce muscular relaxation in about 30 to 60 seconds and has a duration of action of about 2 to 6 minutes.
- Larger doses will produce more prolonged muscular relaxation, but doubling the dose does not necessarily double the duration of relaxation.
- Supplementary doses of Suxamethonium of 50% to 100% of the initial dose administered at 5 to 10 minute intervals will maintain muscle relaxation during short surgical procedures performed under general anaesthesia.
- For prolonged surgical procedures, Suxamethonium may be given by intravenous infusion as a 0.1% to 0.2% solution, diluted in 5% glucose solution or sterile isotonic saline solution, at a rate of 2.5 to 4 mg per minute. The infusion rate should be adjusted according to the response of individual patients.
- The total dose of Suxamethonium given by repeated intravenous injection or continuous infusion should not exceed 500 mg per hour.
Pediatric population
- Infants and young children are more resistant to Suxamethonium compared with adults.
- The recommended intravenous dose of Suxamethonium for neonates and infants is 2 mg/kg. A dose of 1 mg/kg in older children is recommended.
- When Suxamethonium is given as intravenous infusion in children, the dosage is as for adults with a proportionately lower initial infusion rate based on body weight.
- Suxamethonium may be given intramuscularly to infants at doses up to 4 to 5mg/kg and in older children up to 4 mg/kg. These doses produce muscular relaxation within about 3 minutes. A total dose of 150 mg should not be exceeded.
Elderly
- Dosage requirements of suxamethonium in older patients are comparable to those for younger adults.
- The elderly may be more susceptible to cardiac arrhythmias, especially if digitalis-like drugs are also being taken.
Dosage in hepatic impairment: Termination of the action of suxamethonium is dependent on plasma cholinesterase, which is synthesised in the liver. Although plasma cholinesterase levels often fall in patients with liver disease, levels are seldom low enough to significantly prolong suxamethonium-induced apnoea.
Dosage in renal impairment: A normal single dose of Suxamethonium chloride Injection may be administered to patients with renal insufficiency in the absence of hyperkalaemia. Multiples or larger doses may cause clinically significant rises in serum potassium and should not be used.
Dosage in patient with reduced plasma cholinesterase: Patients with reduced plasma cholinesterase activity may experience prolonged and intensified neuromuscular blockade following administration of suxamethonium. In these patients, it may be advisable to administer reduced dosages of Suxamethonium
chloride Injection.
Monitoring advice: Monitoring of neuromuscular function is recommended during infusion or if Suxamethonium chloride Injection is to be administered in relatively large cumulative doses over a relatively short period of time in order to individualise dosage requirements.
Method of administration
The usual method of Suxamethonium chloride Injection administration is by bolus intravenous injection. It can also be given via intramuscular bolus injection or intravenous infusion.
Special warnings and precautions for use:
Suxamethonium paralyses the respiratory muscles as well as other skeletal muscles but has no effect on consciousness.
Suxamethonium should be administered only by or under close supervision of an anaesthetist who is familiar with its actions, characteristics and hazards, who is skilled in the management of artificial respiration and only where there are adequate facilities for immediate endotracheal intubation with the administration of oxygen by intermittent positive pressure ventilation.
Cross-sensitivity:
As there is a higher rate of cross-sensitivity with other neuromuscular blocking (both depolarising and non-depolarising) drugs, caution is advised where there is a history of sensitivity to neuromuscular blocking drugs.
Suxamethonium should only be used when absolutely essential in susceptible patients.
Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers.
During prolonged administration of suxamethonium, it is recommended that the patient is fully monitored with a peripheral nerve stimulator in order to avoid overdosage.
Hyperkalaemia:
Suxamethonium increases serum potassium by 0.5mmol/L in normal individuals. This may be significant with pre-existing elevated serum potassium. Patients with burns or certain neurological conditions may develop severe hyperkalaemia. In severe sepsis, the potential for hyperkalaemia may be related to the severity and duration of the infection.
Bradycardia and other cardiac dysrhythmias
In healthy adults, suxamethonium occasionally causes a mild transient slowing of the heart rate on initial administration.
Bradycardias are more commonly observed in children or if repeated doses are given (both adults and children). Pre-treatment with intravenous atropine or glycopyrrolate can significantly reduce the incidence and/or severity of suxamethonium-related bradycardia.
Suxamethonium can induce cardiac dysrhythmias and arrest. In the absence of hyperkalaemia, ventricular dysrhythmias are rare although patients on cardiac glycosides are at increased risk. The action of suxamethonium on the heart may cause changes in cardiac rhythm including cardiac arrest.
Raised intra-ocular pressure (IOP):
Suxamethonium causes a transient increase in intraocular pressure and should not be used in the presence of penetrating eye injury except where the potential benefits outweigh the injury to the eye.
Cholinesterase deficiency:
Suxamethonium is rapidly hydrolysed by plasma cholinesterase which thereby limits the intensity and duration of the neuromuscular blockade.
Individuals with decreased plasma cholinesterase activity exhibit a prolonged response to suxamethonium.
Prolonged and intensified neuromuscular blockade following Suxamethonium Injection may occur secondary to reduced plasma cholinesterase activity in the following states or pathological conditions:
- Physiological variation as in pregnancy and the purpurium.
- Genetically determined abnormal plasma cholinesterase.
- Severe generalized tetanus, tuberculosis, other severe or chronic infections.
- Following severe burns.
- Chronic debilitating disease, malignancy, chronic anaemia and malnutrition
- End stage hepatic failure, acute or chronic renal failure.
- Auto-immune diseases: myxoedema, collagen diseases.
- Iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass, and as a result of concomitant drug therapy.
Paediatric population:
Caution should be exercised when using suxamethonium in children since paediatric patients more likely to have undiagnosed myopathies or pre-disposition to malignant hyperthermia and rhabdomyolysis, which places them at increased risk of serious adverse events following suxamethonium. Susceptible to bradycardia.
Muscle pains:
Muscle pains are frequently experienced after administration of suxamethonium and most commonly occur in ambulatory patients undergoing short surgical procedures under general anaesthesia. There appears to be no direct connection between the degree of visible muscle fasciculation after Suxamethonium administration and the incidence or severity of pain. The use of small doses of non-depolarising muscle relaxants given minutes before suxamethonium administration has been advocated for the reduction of incidence and severity of suxamethonium-associated muscle pains. This technique may require the use of doses of suxamethonium in excess of 1mg/kg to achieve satisfactory conditions for endotracheal intubation.
Myasthenia gravis:
It is inadvisable to administer suxamethonium to patients with advanced myasthenia gravis. Although these patients are resistant to suxamethonium they develop a state of atypical phase II block which can result in delayed recovery.
Myasthenic Eaton-Lambert syndrome:
Patients with the myasthenic Eaton-Lambert syndrome are more sensitive than normal to suxamethonium and the dose should be reduced in these patients.
Patients in remission from myasthenic Eaton-Lambert syndrome may however demonstrate a normal response to suxamethonium.
Prolonged use:
If Suxamethonium is given over a prolonged period, the characteristic depolarizing neuromuscular (or Phase I) block may change to one with characteristics of a non-depolarising (or Phase II) block. Although the characteristics of a developing Phase II block resemble those of a true non-depolarising block, the former cannot always be fully or permanently reversed by anticholinesterase agents. When a Phase II block is fully established, its effects will then usually be fully reversible with standard doses of neostigmine accompanied by an anticholinergic agent.
Tachyphylaxis occurs after repeated doses.
Use in other conditions:
This agent should be used with caution in ill and cachectic patients, in patients with acid-base disturbances or electrolyte imbalance, parenchymatous liver disease, obstructive jaundice, carcinomatosis, in those in contact with certain insecticides, e.g. organophosphorous compounds and in those receiving therapeutic radiation.
Suxamethonium should be used with caution in patients with fractures or muscle spasms because the initial muscle fasciculations may cause additional trauma.
Muscarinic effects of this compound e.g. increased bronchial and salivary secretions may be prevented by atropine.
When this agent is given as an infusion, this should be monitored with care to avoid overdose.
Suxamethonium has no direct effect on the myocardium, but by stimulation of both autonomic ganglia and muscarinic receptors suxamethonium may cause changes in cardiac rhythm, including cardiac arrest.
Use with other solutions:
Suxamethonium should not be mixed with any other agent in the same syringe (particularly thiopentone/thiopental).
Undesirable effects
There is limited clinical documentation that can be used as support for determining the frequency of adverse reactions.
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: Very common (≥ 1/10); Common (≥ 1/100 to <1/10), Uncommon (≥ 1/1,000 to <1/100); Rare (≥ 1/10,000 to <1/1,000); Very rare (<1/10,000).
|
System organ class |
Frequency |
Undesirable effects |
|
Immune system disorders |
Very Rare |
Anaphylactic reactions |
|
Eye disorders |
Common |
Increased intraocular pressure |
|
Cardiac disorders |
Common |
Bradycardia,tachycardia |
|
Rare |
||
|
Arrhythmias (including ventricular arrhythmias), cardiac arrest |
||
|
Vascular disorders |
Common |
Skin flushing Hypertension and hypotension have also been reported. |
|
Respiratory, thoracic and mediastinal disorders |
Rare |
Bronchospasm, prolonged respiratory depression, apnoea. |
|
Gastrointestinal disorders |
Very Common |
Increased intragastric pressure Excessive salivation has also been reported |
|
Skin and subcutaneous tissue disorders |
Common |
Rash |
|
Musculoskeletal and connective tissue disorder |
Very common |
Muscle fasciculation, post-operative muscle pains. |
|
Common |
Myoglobinaemia, myoglobinuria |
|
|
Rare |
Trismus |
|
|
General disorders and administration site conditions |
Very rare |
Malignant hyperthermia |
|
Investigations |
Common |
Transient blood potassium increase |
Drug Interaction:
Certain drugs or chemicals are known to reduce normal plasma cholinesterase activity and may therefore prolong the neuromuscular blocking effects of suxamethonium. These include:
Antibacterials
Enhanced effects of suxamethonium with aminoglycosides, clindamycin, polymyxins vancomycin and piperacillin.
Antimalarials
Quinine and chloroquine - effects of suxamethonium possibly enhanced.
Antipsychotics
Enhanced effects of suxamethonium with promazine, promethazine, chlorpromazine, phenelzine, and lithium carbonate.
General anaesthetic agents
Propofol – increased risk of myocardial depression and bradycardia. Volatile liquids General anaesthetic: halothane, enflurane, desflurane, isoflurane, diethylether and methoxyflurane have little effect on the phase I block of Suxamethonium injection but will accelerate the onset and enhance the intensity of a Phase II suxamethonium-induced block. Ketamine and propanidid – possible prolonged block.
Analgesics
Enhanced effects of suxamethonium with morphine, morphine antagonists, pethidine, pancuronium and propanidid
Anti-arrhythmics
Lidocaine (lignocaine) – enhanced and prolonged neuromuscular blockade. Quinidine, procainamide and verapamil. beta-blockers – enhanced and prolonged neuromuscular blockade.
Local anaesthetics
Enhanced effects of suxamethonium with procaine, cocaine, chloroprocaine, and lidocaine.
Cardiac glycosides
Possible increased risk of bradycardia and other dysrhythmias, including ventricular dysrhythmias and cardiac arrest. More susceptible to the effects of suxamethonium exacerbated by hyperkalaemia.
Cytotoxics
- Enhanced effects of suxamethonium with cyclophosphamide, thiotepa, other alkylating agents (chlorethamine: tretamine), triethylene-melamine.
- Immunomodulators: Azathioprine – prolonged neuromuscular blockade
- Magnesium: Parenteral magnesium – enhanced neuromuscular blockade
- Metoclopramide: Enhanced effects of suxamethonium
- Parasympathetics: Enhanced effects of suxamethonium with: donepezil, edrophonium, galantamine, neostigmine, pyridostigmine, physostigmine, rivastigmine, and tacrine hydrochloride.
- Sympathomimetics (beta agonists): bambuterol and terbutaline – enhanced effects of suxamethonium.
- Anti-histamines: Diphenhydramine – enhanced effects of suxamethonium
- Drugs known to reduce normal plasma cholinesterase
In addition to the drugs listed above, certain other drugs and chemicals are known to reduce normal plasma cholinesterase activity and therefore may prolong the neuromuscular effect of suxamethonium.
These include: organophosphorous insecticides, metriphonate, trimethaphan, ecothiopate eye drops (prolonged apnoea after suxamethonium has occurred), and selective serotonin reuptake inhibitors (SSRI).
The following have potentially adverse effects on plasma cholinesterase activity: aprotinin, oestrogens and oral contraceptives, oxytocin, high-dose steroids.
- Liver disease, cancer, pregnancy, dehydration, electrolyte imbalances and overdosage (due to excessive production of succinylmonocholine) may also prolong the action of suxamethonium.
Pregnancy and Breast-feeding:
Suxamethonium has no direct action on the uterus or other smooth muscle structures. In normal therapeutic doses it does not cross the placental barrier in sufficient amounts to affect the respiration of the infant. Suxamethonium should nevertheless not be administered to pregnant women unless the expected benefit of its use outweighs possible risks to the foetus.
The benefits of the use of suxamethonium as part of a rapid sequence induction for general anaesthesia normally outweigh the possible risk to the foetus.
Plasma cholinesterase levels may fall during the first trimester of pregnancy to about 70-80% of their pre-pregnancy values; a further fall to about 60-70% of the pre-pregnancy levels occurs within 2-4 days after delivery. Plasma cholinesterase levels then increase to reach normal over the next 6 weeks. Consequently, a high proportion of pregnant and puerperal patients may exhibit mildly prolonged neuromuscular blockade following Suxamethonium Injection.
It is not known whether suxamethonium or its metabolites are excreted in human milk therefore, caution should be exercised following administration of suxamethonium to nursing mothers.
Effects on ability to drive and use machines:
This precaution is not relevant to the use of Suxamethonium Injection. Suxamethonium will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthesia apply.
Overdose:
Symptoms:
Apnoea and prolonged muscle paralysis are the main and serious effects of overdosage.
Management:
- It is essential to maintain a patent airway together with assisted ventilation until spontaneous respiration returns.
- Neostigmine and other anticholinesterase drugs are not antidotes to suxamethonium but would normally intensify the depolarisation effect. However, in some cases when the action of suxamethonium is prolonged, the characteristic depolarising (Phase I) block may change to one with characteristics of a nondepolarizing (Phase II) block.
- The decision to use neostigmine to reverse a phase II suxamethonium-induced block depends on the judgement of the clinician in the individual case. Valuable information in regard to this decision will be gained by monitoring neuromuscular function.
- To investigate this possibility, the short-acting anticholinesterase drug, edrophonium, may be given intravenously. If an obvious improvement is maintained for several minutes, neostigmine may be given with atropine. Subsequently, the patient should be observed carefully and if apnea recurs, a further dose of neostigmine is indicated.
- Transfusion of fresh whole blood, frozen plasma, or other source of pseudocholinesterase will help the destruction of suxamethonium.