Succinylcholine or Suxamethonium: Concept of depolarizing muscle relaxant
• Suxamethonium or succinylcholine (Sch) is made up of two molecules of acetylcholine joined by their acetyl groups. It should be stored at 2 to 8oC and has a shelf life of 2 years.
• Succinylcholine is metabolized by butyryl cholinesterase, also known as plasma cholinesterase and pseudocholinesterase.
• As this enzyme is not present in the synapse, Sch is metabolized only after it diffuses out to plasma. Thus, Sch induced persistent stimulation of NM receptors causes persistent depolarization of postsynaptic membrane and inactivation of sodium channel, which causes muscle relaxation. This is called as phase I block, which is worsened by ACHE inhibitors.
• At further higher doses there can be receptor desensitization mimicking tachyphylaxis called as phase II block, which can be reversed by increasing Ach in synapse by ACHE inhibitors.
• Sch is the shortest and fastest acting muscle relaxant and hence it is commonly used for intubation.
• Persistent depolarization of post synaptic membranes can cause hyperkalemia and contraction of muscles leading to side-effects mentioned below.
1. Increased muscle contraction:
Fasciculations
Masseter spasm
Myalgia
2. Muscle damage – Raised myoglobin and CPK
3. Increased abdominal muscle contraction - Increased intragastric pressure
4. Increased oxygen consumption and carbon dioxide production due to muscle contraction cause cerebral vasodilation - Increased ICP
5. Increased tonic myofibrils contraction and dilation of choroidal blood vessels - Increased IOP
6. Increased catecholamine release - Increased blood pressure and Ventricular tachyarrhythmia
7. Depolarization of muscles - Hyperkalemia
8. Cardiac muscarinic receptor stimulation - Sinus bradycardia and Junctional rhythms
9. Stimulation of ryanodine receptor - Malignant hyperthermia
• Myalgia is seen usually in females, after minor surgeries and ambulatory patients. Prostaglandin inhibitors can decrease the incidence of myalgia.
• Fasciculations can be prevented by precurarization, i.e. premedication with an NDMR.
• Hyperkalemia is a side-effect that can cause refractory asystole and hence other conditions with increased potassium levels are an absolute contraindication. These are conditions like burn patients, myopathy, neuropathy, spinal cord damage etc.
• Succinylcholine is the most common cause of anaphylaxis during anesthesia.
• Patients with atypical pseudocholinesterase due to genetic variability are unable to metabolize Sch and hence there is prolonged apnea. Dibucaine number is used to find out the amount of normal enzyme; dibucaine a local anesthetic inhibits 80% of normal enzyme but only 20% of abnormal enzyme. If it is said that the dibucaine number in a patient is 80, it means dibucaine inhibits 80% of normal enzyme.
Dibucaine number Pseudocholinesterase type Response to Sch
70-80 Homozygous typical Normal
50-60 Heterozygous atypical Abnormal
20-30 Homozygous atypical Abnormal
• ACHE inhibitors like neostigmine can also inhibit pseudocholinesterase and hence prolong the effect of Sch.
