title: Precurarization and priming: a theoretical analysis of safety and timing.
abstract: The priming principle suggests that the onset of neuromuscular block may be accelerated if an intubating dose is preceded by a priming dose administered a few minutes earlier. We thought it would be instructive to use a pharmacodynamic/pharmacokinetic model to estimate the risk associated with different priming doses and intervals. In any normal population, there is wide variability in the response to neuromuscular blocking drugs. For most relaxants, the coefficient of variation for the 50% effective dose (ED(50)) approximates 20%-25%. Thus, 1 patient in 50 (-2.05 SD) may have an ED(50) only half of the commonly cited value. By using published pharmacodynamic/pharmacokinetic data, we calculated the effect of administering 10%, 20%, or 30% of the ED(95) on the response of the adductor pollicis muscle in a population normally distributed with respect to drug sensitivity. A dose equivalent to 10% of the ED(95) will rarely produce a measurable neuromuscular effect. As this dose is increased, the potential for clinical weakness rapidly escalates. In 1 in 50 individuals, the usual recommendation of 10% of the intubation dose will produce measurable neuromuscular depression. For vecuronium, the optimal priming interval is 5 min. The safety and dependability of the priming principle is very much subject to the laws of probability.
  
  
  CONCLUSIONS
  When using the priming principle to accelerate the onset of neuromuscular block, the initial dose should not exceed 10% the drug's ED(95). For drugs other than rocuronium, the optimal priming interval is not <5 min.
authors.affiliation: Department of Anesthesiology, Saint Vincents Hospital & Medical Center of New York, New York, New York 10011, USA. akopman@rcn.com.
authors.forename: A F
authors.initials: AF
authors.lastname: Kopman
authors.forename: N A
authors.initials: NA
authors.lastname: Khan
authors.forename: G G
authors.initials: GG
authors.lastname: Neuman
mesh_terms: D000732:Androstanols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007206:Individuality; D008954:Models, Biological; D019148:Neuromuscular Blockade / Q000379:methods*; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077123:Rocuronium; D014673:Vecuronium Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D014673:Vecuronium Bromide; D000077123:Rocuronium