Physiology and pharmacology of neuromuscular transmission, with special reference to the possible consequences of prolonged blockade

Conclusion

There is a deliberate element of flight of fancy in the foregoing discussion, which is intended to illustrate that prolonged and continuous use of neuromuscular blocking drugs may produce pre- or postjunctional changes, or both that would not be predicted from a knowledge of their acute pharmacology. Such effects could result in a gradual development of either decreased or increased effectiveness, depending upon the nature of the long term changes. In addition, accumulating metabolites of the parent drug, especially in those critically ill patients who undergo intensive care, might give rise to untoward effects. Indeed, Segredo et al. [30] attribute prolonged block by vecuronium in intensive care patients, not to vecuronium itself, but to its first metabolite, the 3-desacetyl derivative, which accumulates because of renal failure. This is obviously an important contributing factor, although there is no reason to suppose that it is the only mechanism involved in all cases.

In the past, neuromuscular-blocking drugs have not been tested during preclinical development for their potential long term use in intensive care. Consequently, if and when it is necessary to use them clinically in this way, eachoccasion should be regarded as a new experiment, to be accompanied by careful monitoring of their effects. In this way, any changes in sensitivity to the drugs in either direction, or other unusual effect, can be detected as early as possible and appropriate adjustments made. In the meantime, new drugs should be designed and developed in the laboratory, with intensive care especially in mind.