Pharmacokinetic study (phase I-II) of a new dobutamine formulation in preterm infants immediately after birth.

BACKGROUND: Dobutamine is particularly suited to treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in the preterm infant. Knowledge of the elimination half-life is essential to estimate the steady state when its efficacy/safety can be evaluated. METHODS: Analysis of pharmacokinetic data in ten preterm newborns treated with a new neonatal formulation of dobutamine (IMP) after screening for haemodynamic insufficiency within the first 72 h from birth. Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h). IMP concentration in each sample was measured by ultra-high performance liquid chromatography with electrochemical detection. RESULTS: Median duration of IMP infusion was 37.7 h (IQR 21.2). Calculated IMP half-life ranged between 3.06 and 36.1 min (median 10.6 min), leading to a time to reach the steady-state concentration between 15 min and >2 h. Adverse events were not related to IMP. CONCLUSIONS: The wide variability in dobutamine metabolism in preterm infants requires awareness about the risk of under- or overtreatment. A delay of up to 3 h might be required before drawing blood samples to evaluate the effective dose. IMPACT: Small trials suggest dobutamine as the optimal drug in the preterm infant with haemodynamic insufficiency after birth. Age-related differences in drug pharmacokinetics may result in suboptimal treatments. The lack of formal studies in preterms results in inadequate data on efficacy and safety. This study provides data on the variability of the elimination half-life of dobutamine in the very preterm infant during transitional circulation. There is a wide variation in the time to reach the plasma concentration corresponding to steady state, the moment when its efficacy/safety can be reliably evaluated. This information is crucial for planning future trials on cardiovascular support.

Coronectomy practice. Paper 2: complications and long term management.

Coronectomy was developed to reduce the incidence of iatrogenic injury to the inferior dental nerve, which can be a result of routine mandibular third molar surgery, but it is not widely accepted despite early studies that all showed positive results. This two-part paper looks at the technique in more detail to help clinicians gain a better understanding of the procedure. The first part dealt in detail with technical aspects. This one will consider the management of common complications.

Coronectomy practice. Paper 1. Technique and trouble-shooting.

Coronectomy is a technique that reduces morbidity of the nerve after operation on high-risk mandibular third molars. This two-part paper aims to give an overview of the technique and a description of common problems that can be encountered during and after operation. In this paper we discuss the technique as an overview and then each type of impaction more specifically. We also explore common problems encountered during the procedure and their subsequent management.