ABSTRACT
OBJECTIVES: The purpose of this study was to assess the appropriateness of weight-based dosing of continuous intravenous infusion of fentanyl in overweight/obese versus normal-weight children admitted to the pediatric intensive care unit (PICU). METHODS: This retrospective, pilot study included 5- to 12-year-old children admitted to the PICU over a 2-year period who received continuous intravenous infusion fentanyl for ≥ 4 days. The overweight/obese group included children with a body mass index (BMI) ≥ 85th percentile, while the control group included children with BMI < 85th percentile. The primary objective was to compare the number of fentanyl continuous intravenous infusion dosage changes required per day to achieve adequate sedation between groups. Secondarily, opioid withdrawal symptoms following the discontinuation of fentanyl and concomitant sedative/analgesic regimens were analyzed between groups. Student t tests and chi-square analyses were performed as appropriate, with an a priori alpha of p≤0.05. RESULTS: Sixteen normal-weight and 15 overweight/obese patients with 18 and 16 individual infusions were identified, respectively. No statistical difference was found between groups for the number of dosage changes per day, 0.92 versus 0.69 (p=0.16). Five patients in each group experienced withdrawal (p=0.71). The total number of concomitant bolus doses received was greater in the overweight/obese group but did not reach statistical significance. CONCLUSIONS: There was a numerical, but statistically nonsignificant difference in the number of sedative/analgesic bolus doses and dosing changes per day between groups. Larger studies are warranted to determine the optimal dosing strategy for continuous intravenous infusion fentanyl in overweight/obese children.
ABSTRACT
OBJECTIVE: To review the pharmacology, toxicology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines for lofexidine, an alpha(2)-agonist, for opioid detoxification. DATA SOURCES: Primary literature was identified through a MEDLINE search (1950-September 2009), EMBASE (1988-July 2009), International Pharmaceutical Abstracts (1970-September 2009), and the Cochrane Library (1996-September 2009) using the key words lofexidine and opioid withdrawal. Abstracts were included in the absence of published results of studies. STUDY SELECTION AND DATA EXTRACTION: Studies published in English-language literature reporting on animal and human pharmacology, toxicology, and pharmacokinetics were included in addition to clinical trials using lofexidine for opioid detoxification in comparison to placebo or active controls. DATA SYNTHESIS: Lofexidine is an alpha(2)-agonist structurally related to clonidine. It is not an effective antihypertensive agent; however, it decreases the sympathetic outflow responsible for many opioid withdrawal symptoms. Nine clinical studies were reviewed representing 354 patients receiving lofexidine including a recent Phase 3 clinical trial. Eight studies involved comparisons of lofexidine to an opioid receptor agonist or clonidine for opioid detoxification. In these trials, lofexidine dosing was titrated to a maximum of 1.6-3.2 mg/day in divided doses for a total of 5-18 days. The data suggest that lofexidine has positive efficacy in reducing opioid withdrawal symptoms and is at least as effective as the opioid receptor agonists utilized for detoxification. Not all withdrawal symptoms are alleviated by alpha(2)-agonists, with many patients complaining of insomnia and aching. The most common adverse event with lofexidine in the Phase 3 trial was insomnia. Hypotension was also reported; however, the studies comparing clonidine with lofexidine suggest decreased incidence and severity of adverse events with lofexidine. CONCLUSIONS: Lofexidine appears to be a promising agent for opioid detoxification. If approved, it would be the first nonopioid agent approved for this indication. Further large-scale controlled studies are needed to identify the safest, most effective dosage regimen required to achieve opioid detoxification.
