On the interaction between a neuromuscular blocking agent and regulation of breathing during hypoxia

Abstract

It was previously generally agreed that a mechanical train-of-four (TOF) ratio >0.70 represented an adequate recovery of respiratory function after neuromuscular blockade. Normal respiratory parameters at this level of recovery and during air breathing support this view. We doubted whether this level of recovery also was associated with a normal response to hypercarbic or hypoxic challenge.

The aim of the first study was to investigate the influence of a partial neuromuscular block on the ventilatory responses to hypercarbia and hypoxemia. We found that a vecuronium-induced partial neuromuscular block, corresponding to a TOF-ratio of 0.70 is associated with a normal resting ventilation and ventilatory response to hypercarbia while a marked reduction in the ventilatory response to hypoxaemia was found. We conclude that a mechanical TOF ratio of 0.70 following vecuronium is associated with an inadequate ventilatory response to hypoxaemia.

These findings, and the theory that they were caused by an interaction between vecuronium and the normal response to hypoxemia at the peripheral chemoreceptors of the carotid body, lead to our second study. Here we studied the effects of close carotid body injections of vecuronium on phrenic nerve activity, at different states of oxygenation, in anaesthetised and mechanically ventilated adult rabbits. A close carotid body injection of vecuronium reduced the hypoxia-induced increase in phrenic nerve activity. We conclude that this was most likely caused by a vecuronium-induced depression of carotid body chemosensitivity, but that further investigations were necessary to confirm this hypothesis.

To elucidate whether this reduced response to hypoxic challenge was caused by an effect of Vecuronium on the peripheral chemo receptors, and not by a central effect, we designed a third study. This time we excluded central regulation by directly recording single fibre sinus nerve activity. The effect of systemic administration of vecuronium on a single fibre preparation of the carotid sinus nerve, was studied in seven mechanically ventilated rabbits. Our findings showed that systemic administration of vecuronium reversibly depresses the chemoreceptor function of the carotid body as measured on a single fibre afferent chemoreceptor preparation during hypoxia. We conclude that vecuronium, in addition to muscular paralysis, causes depression of carotid body chemoreceptor function during hypoxia and that the depression recovers spontaneously.

To further demonstrate that the reduction in chemoreceptor activity observed in the previous experiments was being caused by an effect of the neuromuscular blocking agent on the peripheral receptor it was necessary to completely isolate the carotid body and sinus nerve from the rest of the organism. An isolated carotid body preparation with adjacent sinus nerve was used. Nicotine-induced carotid body responses were significantly depressed by the neuromuscular blocking agents vecuronium and atracurium. Increased dose caused an increased depression. We conclude that atracurium and vecuronium depress nicotine-induced chemoreceptor responses of the carotid body in a dose dependent manner and note that equipotent neuromuscular blocking concentrations give rise to a similar degree of chemoreceptor depression. Our findings have contributed to a change in attitude towards the clinical consequences of residual neuromuscular block. A TOF ratio of >=0.90 is now recommended for safe extubation, at which levels our research indicates that the hypoxic ventilatory response has recovered.