Cumulation and flexibi l - ity with infusions o f neuromuscular blocking drug s

HE major problem addressed in neuro muscular research over the past 60 yr ha s been to provide a fast onset/rapid recover y nondepolarizing agent without side effects . The driving force behind this agenda is a patient saf e ty problem, that is the possibility to secure the airwa y within 1-1.5 min and a rapid (5-10 min) recover y should intubation fail. This quest for new agents ha s not produced the perfect drug, but over the pas t decades, a trend towards faster onset, shorter duration compounds can be observed . The availability of short acting neuromuscular block ers has another benefit quite separate from the rapid on/off property. It allows the clinician to increase o r decrease rapidly the intensity of surgical relaxation , depending on actual need, and this is best accomplished when neuromuscular blocking drugs are given as infu sions. The depth of anesthesia required for a given su rgical procedure is not constant. The need for muscl e relaxation also varies throughout surgery. It is probabl y highest at the time of tracheal intubation, is moderat e at peritoneal incision and closure, and lowest at skin closure. These rough guidelines depend on the patien t and the procedure. Infusions aside, anesthesiologist s commonly inject neuromuscular relaxants according to need. A relatively large dose is given at the beginning for tracheal intubation, with no response seen at th e adductor pollicis with indirect nerve stimulation. A somewhat more modest level of relaxation is needed fo r the start of the surgery, less relaxation is usually presen t for most of the procedure, and top-up doses are often needed for closure. Full recovery is a must at the end o f the case . Provided that recovery is rapid, there is, however , very little disadvantage in keeping relaxation relativel y constant at a deep level throughout surgery. Most mod ern neuromuscular relaxants have virtually no cardio vascular effects, so an overdose has few, if any, immed i ate consequences. This is not the case for narcotics , inhalational agents and intravenous anesthetics, all o f which produce hypotension if a large dose is admini stered. Moreover, the dose of muscle relaxant can b e adjusted by using a nerve stimulator. Thus, an attractiv e solution for the administration of muscle relaxants is b y infusion, adjusted to fit most requirements during th e case (usually one twitch in the train-of-four). The basi c properties of the perfect neuromuscular blocking drug for administration by infusion can be imagined easily : (1) fast onset to have the option to increase relaxation quickly if required; (2) rapid recovery because neuro muscular function must return to normal after anesth e sia; and (3) constant infusion rate to keep the effec t constant with time. The first two of these properties ar e part of what is considered essential for an ideal neuro muscular blocking drug. In addition, a constant infu sion rate allows profound relaxation without concern for recovery, with the anesthesiologist’s attention