Pancuronium bromide (PB) is used in neonates and pregnant women to induce limp, flaccid paralysis in order to allow mechanical ventilation during intensive care. Such non-depolarising neuromuscular blocking drugs are administered to approximately 0.1 % of all human births in the UK.

In this study we examined the effects of PB administered via direct application to the chorioallantoic membrane on the skeletal development in White Leghorn chicken embryos. This involved daily administration (from day 10 gestation, for 1, 3, or 7days) of sterile PB in Tyrode solution (controls received Tyrode solution alone), weighing and examination of chicks killed humanely, before and after Alcian blue/Alizarin red staining of developing cartilage and bone skeletal elements. Direct video-imaging evidence of the efficacy of neuromuscular blockade has previously been described (Osborne et al. 2002).

We found that PB treatment produced skeletal deformities associated with significant reduction in longitudinal growth of all appendicular elements. The diverse range of fixed positional deformities, ranging from hyperflexion to hyperextension of individual joints such as the first inter-phalangeal joint, was associated with greater cartilage to bone ratios after prolonged periods of immobilsation (day 14 and 18), indicating a preferential reduction in osteogenesis. PB treatment also consistently increased incidence of knee joint flexion and tibiotarsal joint hyperextension. In addition to limb, spinal and craniofacial deformities, flaccid immobility appears to convert the normal geometric pattern of weight gain to a simple arithmetic accretion. Our preliminary results also indicate that a single PB dose, administered on day 10 produces sustained long-term immobility in 60 % of chicks at day 18. Intriguingly, similar positional deformities were seen in both these chicks, and those exhibiting recovery in normal motility (30 %) and weight gain.

This novel study highlights the potentially harmful effects of pharmacologically induced flaccid immobility on chick embryonic skeletal development. Whilst in ovo avian development clearly differs from human, our findings may have implications for the fetus and the premature and term neonate receiving such non-depolarising neuromuscular blocking drugs.