Research Coordinator/ Research Assistant Nemours Alfred I duPont Hospital for Children Nemours Alfred I duPont Hospital for Children Wilmington, Delaware, United States
Background: Cerebral palsy (CP) represents one of the most common motor impairment disorders and occurs in about 3 per 1000 children. The long term effects of CP often result in the need for surgery. Neuromuscular blocking agents (NMBAs), like rocuronium (ROC) are used to facilitate muscle relaxation in the patient for intubation. Previous studies indicate that children with CP exhibit resistance to certain NMBAs; however, details regarding ROC use and specific mechanisms to explain resistance have yet to be elucidated.
Objective: We evaluated ROC dose requirements derived from surgical and medical records during surgery in conjunction with measures of CP severity and factors suspected to influence NMBA dosing.
Design/Methods: Participants with spastic CP (n=64) and controls (n=72) were enrolled in an IRB approved study at the Nemours- Alfred I duPont Hospital for Children. Subjects with known genetic disorders or syndromes were excluded. Skeletal muscle samples collected during surgery were flash frozen for immunofluorescense 3D analysis of NMJ organization. Demographic information, gross motor function classification system (GMFCS) scores, use of anticonvulsants, serum analytes indicative of liver function, and birth history were obtained from the medical record.
Results: The average intubating dose of ROC for control subjects (0.64+0.03) was similar to the recommended dosing of 0.6 mg/kg of body weight. Subjects with CP required significantly elevated doses of ROC (1.00+0.08, p< 0.0001) whether they were on chronic anticonvulsant therapy (1.21+0.13, p<0.0001) or not (0.88+0.11, p=0.04). ROC dosing for patients with CP who were not on anticonvulsant therapy exhibited a significant correlation with the subject’s GMFCS score (Spearman’s rho=0.329, p=0.035). Interestingly, patients with CP who were full term or of normal birth weight had higher intubating ROC doses than their pre-term or low birth weight counterparts (p=0.002 and p=0.020, respectively). Conclusion(s): ROC dosing for intubation was elevated in children with spastic CP regardless of whether they were receiving anticonvulsant therapy. Anticonvulsant use substantially elevated ROC dosing, but even among children without anticonvulsants ROC dose positively correlated with GMCS functional score indicating that elevated ROC is associated with higher degrees of motor affect. Further research is needed to elucidate the mechanism of NMBA resistance in CP.
Authors/Institutions: Stephanie K. Lee, Nemours - Alfred I duPont Hospital for Children, Wilmington, Delaware, United States; Karyn Robinson, Nemours - Alfred I duPont Hospital for Children, Wilmington, Delaware, United States; Robert E. Akins, The Nemours Foundation, Wilmington, Delaware, United States