Immediate Effects of Use of Recombinant Bone Morphogenetic Protein in Children Having Spinal Fusion and Refusion Procedures in United States.

STUDY DESIGN: Retrospective study of Nationwide Inpatient Sample (NIS). OBJECTIVE: The objective of this study is to estimate the prevalence of complications in children who had insertion of recombinant human bone morphogenetic protein (rhBMP) at the time of spinal fusion procedures (SFP) and to examine if the use of rhBMP is associated with an increased risk of complications. SUMMARY OF BACKGROUND DATA: Use of rhBMP for SFP has been associated with conflicting safety profile reports in adults. METHODS: NIS (years 2004-2010) was used. All patients with age  < 18 years who had a SFP during hospitalization with or without insertion of rhBMP were selected. Complications were selected based on a literature review of studies examining outcomes of SFP. Association between insertion of rhBMP and occurrence of complications was examined by multivariable logistic regression models. RESULTS: Of the 72,898 children who underwent SFP, 7.1% children had insertion of rhBMP. Overall complication rate was 14.34% (15.2% in rhBMP group and 14.3% in no-rhBMP group). There was no statistically significant difference in the overall complication rate [odds ratio (OR) = 1.08, 95% confidence intervals (CI) = 0.89-1.30] or among 14 different complications between rhBMP and no-rhBMP groups. Children who had rhBMP were associated with higher odds for "other infections" (OR = 2.09, 95% CI = 1.26-3.48, P = 0.004) when compared with their counterparts. CONCLUSION: Despite the lack of Food and Drug Administration approval, rhBMP was not infrequently used in pediatric SFP. In this large retrospective study using administrative data, the use of rhBMP in children during SFP was not associated with higher risks for majority of assessed complications with the exception of "other infections". Future studies must examine the long-term impact of use of rhBMP in children with SFP. LEVEL OF EVIDENCE: 3.

Pharmacology of inotropic agents in infants and children.

Inotropic agents are drugs which increase the stroke work of the heart at a given pre-load and after-load. All of these agents work through a final common pathway involving the modulation of calcium interactions with various myocardial contractile proteins. The agents employed with pediatric patients include the cardial glycosides, catecholamine beta-agonists and the selective phosphodiesterase III inhibitors. Digoxin is the prototypic cardiac glycoside which has a long history of safe and effective use in infants and children. Its utility in improving right ventricular dysfunction in patients with cor pulmonale leading to biventricular dysfunction makes it ideally suited to the pediatric population. Monitoring digoxin pharmacokinetics in infants is confounded by the presence of an endogenous digoxin-like substance. Nevertheless, the drug is well suited for subacute and chronic myocardial support. In contrast, the catecholamines are the drugs of choice for acute intervention. Their pharmacokinetics permit rapid dosing titration. In infants and children the greatest experience has been accrued with dopamine, a mixed alpha- and beta-agonist but both epinephreine and norepinephrine are being used with increasing frequency as the need for drugs with increased potency and pressor activity becomes more common. The phosphodiesterase inhibitors amrinone and milrinone are the newest additions to our therapeutic armamentarium. In addition to their modest inotropic effects, amrinone and to a greater extent, milrinone offer significant pulmonary vasodilatation as part of their therapeutic package. These effects occur with little or any impact on myocardial oxygen consumpton while their lusitropic effects enhance relaxation in hypertrophied ventricular muscle. Of the two agents milrinone is probably preferred due to its greater therapeutic index and shorter elimination half-life. All of these agents remain important tools in the care of critically ill infants and children. The rational use of these drugs based upon their pharmacokinetic and pharmacodynamic properties is essential to achieve their optimal effects.