BACKGROUND: Although the respiratory muscles (the diaphragm and the laryngeal adductors) recover from paralysis more rapidly than does the adductor pollicis, patients can develop complete paralysis of the respiratory muscles, but not of the adductor pollicis, after bolus administration of vecuronium. The authors used a pharmacodynamic model not requiring muscle relaxant plasma concentrations to reconcile these findings. METHODS: The pharmacodynamic model is based on the traditional model, in which: (1) vecuronium concentration at the neuromuscular junction (C(effect)) is a function of the plasma concentration versus time curve and a rate constant for equilibration between plasma and the neuromuscular junction (k(eo)); and (2) effect is a function of C(effect), the steady-state plasma concentration that produces 50% effect (C50), and a factor to explain the sigmoid relationship between concentration and effect. In the absence of vecuronium plasma concentrations, an empiric model (rather than the usual effect compartment model) can be used to mimic the time delay (proportional, but not identical, to 1/k(eo)) between dose and effect. The model can be used to estimate the steady-state infusion rate that produces 50% effect (IR50), equal to the product of C50 and vecuronium plasma clearance; IR50 for different muscle groups then can be compared to assess relative sensitivity. The authors applied this model to published effect data for subjects given 40-70 micrograms/kg vecuronium in whom paralysis of three muscle groups was measured during opioid/propofol anesthesia. RESULTS: For IR50, the ratio of values for the larynx:diaphragm:adductor pollicis was 1.4:1.2:1; for the equilibration constant (inversely proportional to the time delay), the ratio for the respiratory muscles to the adductor pollicis was 2.5:1. CONCLUSIONS: Vecuronium concentrations peak earlier at the respiratory muscles than at the adductor pollicis, possibly the result of greater perfusion to these organs, leading to earlier onset of paralysis. The observation that bolus injection of vecuronium produces greater paralysis of the respiratory muscles than of the adductor pollicis, despite greater resistance of the respiratory muscles, can be explained by differential rates of equilibration between plasma and various muscles.
BACKGROUND: Although the respiratory muscles (the diaphragm and the laryngeal adductors) recover from paralysis more rapidly than does the adductor pollicis, patients can develop complete paralysis of the respiratory muscles, but not of the adductor pollicis, after bolus administration of vecuronium. The authors used a pharmacodynamic model not requiring muscle relaxant plasma concentrations to reconcile these findings. METHODS: The pharmacodynamic model is based on the traditional model, in which: (1) vecuronium concentration at the neuromuscular junction (C(effect)) is a function of the plasma concentration versus time curve and a rate constant for equilibration between plasma and the neuromuscular junction (k(eo)); and (2) effect is a function of C(effect), the steady-state plasma concentration that produces 50% effect (C50), and a factor to explain the sigmoid relationship between concentration and effect. In the absence of vecuronium plasma concentrations, an empiric model (rather than the usual effect compartment model) can be used to mimic the time delay (proportional, but not identical, to 1/k(eo)) between dose and effect. The model can be used to estimate the steady-state infusion rate that produces 50% effect (IR50), equal to the product of C50 and vecuronium plasma clearance; IR50 for different muscle groups then can be compared to assess relative sensitivity. The authors applied this model to published effect data for subjects given 40-70 micrograms/kg vecuronium in whom paralysis of three muscle groups was measured during opioid/propofol anesthesia. RESULTS: For IR50, the ratio of values for the larynx:diaphragm:adductor pollicis was 1.4:1.2:1; for the equilibration constant (inversely proportional to the time delay), the ratio for the respiratory muscles to the adductor pollicis was 2.5:1. CONCLUSIONS:Vecuronium concentrations peak earlier at the respiratory muscles than at the adductor pollicis, possibly the result of greater perfusion to these organs, leading to earlier onset of paralysis. The observation that bolus injection of vecuronium produces greater paralysis of the respiratory muscles than of the adductor pollicis, despite greater resistance of the respiratory muscles, can be explained by differential rates of equilibration between plasma and various muscles.
Authors: P Jacqmin; E Snoeck; E A van Schaick; R Gieschke; P Pillai; J-L Steimer; P Girard Journal: J Pharmacokinet Pharmacodyn Date: 2006-10-19 Impact factor: 2.745