A 70 kg old athlete was posted for surgery, Patient was administered succinylcholine due to unavailability of vecuronium. It was administered in intermittent dosing (total 640 mg). During recovery patient was not able to respire spontaneously & move limbs. What is the explanation -
Ans. is 'b' i.e., Phase 2 blockade produced succinylcholine Patients developing paralysis after prolonged and high dose of succinyl choline is highly suggestive of phase II succinyl choline block.Phase II block with succinylcholine occurs with prolonged and high dose of the drug.(High dose for Sch is 7-10 mg/kg, 30-60 minutes of exposure is considered prolong).Morgan's Anaesthesia 4th/e p. 112The type of succinylcholine block may change into a non depolarizing block following prolonged administration of the drug (phase II block). Transition from a depolarizing to phase II block is gradual and usually occurs after administration of 7-10 mg/kg of succinylcholine. Recovery from a phase II block is much slower.Millers Anaesthesia 6th/e p. 985After administration of 7-10 mg/kg or 30-60 minutes of exposure to succinylcholine, non depolarizing dual or phase II block occursProlonged paralysis with succinylcholine administration may also occur in pseudocholinesterase deficiencyBut in pseudocholinesterase deficiency prolonged paralysis occurs with usual dose of succinylcholine.Succinylcholine is a noncompetitive muscle relaxantNormally muscles contract due to the action of acetylcholine released in the neuromuscular synaptic junctionsAcetylcholine acts by activating its receptors present on motor end plate, and generates action potentialCompetitive Neuromuscular blockers act by blocking the action of acetylcholine and prevents the generation of action potential.On the other hand succinylcholine acts by depolarization of the motor end plate i.e. it activates the acetylcholine receptor present at the motor end plate.At their first application voluntary muscle contracts but as they are not destroyed immediately like acetylcholine the depolarization persist. It might be expected that this prolonged depolarization would cause muscles to remain contracted but this is not so.With prolonged administration, a depolarization block changes to competitive block. Succinylcholine produces neuromuscular block by overstimulation so that the end plate is unable to respond to further stimulation.Neuromuscular block with succinylcholine occurs in two sequential phasesAn initial depolarization of the endplate produces muscle action potentials and fasciculations.Maintained depolarization past the threshold for firing produces Na+ channel inactivation so that muscle action potentials cannot be generated.This is called phase I or depolarization blockIn the continued presence of succinylcholine, the membrane becomes repolarized *Na+ channel inactivation is reversed and muscle membrane excitability is restoredNonetheless, the neuromuscular block persists because of desensitization of Acetylcholine receptorsThis is known as phase II or desensitization blockThe mechanism for phase II block is not completely understood, a series of allosteric transitions in Acetylcholine receptor is suspected.Succinylcholine phase I block changes to phase II block after prolonged administration of the drue usually following 7-10 mg/kg of the drug or 700 mg drug.Pseudocholinesterase deficiencySuccinylcholine is rapidly hydrolyzed by plasma cholinesterase to succinylmonocholine which is pharmacologically inactive.In certain conditions metabolism of succinylcholine to the metabolically inactive succinylmonocholine cannot occur.These are : -Genetic determined inability to metabolize succinylcholineSmall proportion of patients have genetically determined inability to metabolize succinylcholine.In these patients either the plasma cholinesterase is absent or there is an abnormal form of the enzyme presentThe metabolism of succinylcholine is reduced and the patient have prolonged paralysis.An important point to note is that this prolonged paralysis occurs even with usual doses of succinylcholine.Other endogenous and exogenous causesPlasma cholinesterase activity can be reduced by a number of endogenous and exogenous causes such as : -PregnancyLiver diseaseUremiaMalnutritionBurnsPlasma pheresisOral contraceptivesThese conditions usually lead to a slight clinically unimportant increase in the duration of action of succinylcholine.
Pseudocholinesterase deficiency increasing action of syccinylcholine
Phase 2 blockade produced by succinylcholine
Undiagnosed muscular dystrophy and muscular weakness
Muscular weakness due to fasciculation produced by succinylcholine
Depolarising Neuromuscular Blocking Agents