|
Article Excerpt
BOTH BENIGN AND pathologic gastroesophageal reflux disease (GERD) are extremely common in infancy. In a survey of outpatient pediatric practices, two thirds of 4-month-olds regurgitated at least daily. (1) The incidence of GERD is higher in certain medically complicated subpopulations such as premature and neurologically impaired infants and those with congenital malformations. For example, estimates of the incidence of GERD in premature infants range from 40% to 85%. (2,3) These fragile populations, however, may be at the highest risk from adverse effects of the therapy for GERD. Furthermore, although the North American Society of Pediatric Gastroenterology and Nutrition treatment guidelines emphasize the difference between gastroesophageal reflux (GER) and GERD (4) (in which there are complications of GER), the complications of GER remain ill-defined in certain high-risk subgroups such as premature infants. (5-9)
Metoclopramide has been used to treat GERD in infants for several decades. (10-18) However, the recent impetus toward evidence-based prescribing in pediatric populations and reports of adverse drug reactions have spurred public discussion about the efficacy and safety profile of metoclopramide in infants and children. (19-22)
In many practices, metoclopramide has become the standard of care without a rigorous approval process. Although the prevalence of metoclopramide use in infants across inpatient and outpatient settings is ill-defined, it is clear that it is commonly prescribed for infants and children. In the United States, >7 million prescriptions for metoclopramide were dispensed in 2004. In the same year, >30% of the annual outpatient visits in which metoclopramide was mentioned were in the pediatric population (aged 0-16 years). (23) The practice patterns in the prescription of metoclopramide for GERD also vary widely. For instance, in a survey of 57 NICUs in England and Wales, 53% reported using dopamine antagonists such as metoclopramide to treat GERD in premature infants, whereas 47% did not. (6)
Therefore, we conducted a systematic review of the literature of metoclopramide for GERD in infants aged to 23 months as a complement to the Cochrane systematic review (24) of GERD therapies in children, which found both therapeutic benefit and increased adverse effects with metoclopramide treatment. Although the Cochrane review only included randomized trials and evaluated multiple therapies for GERD, we narrowed the scope of the research, focusing only on metoclopramide therapy for GERD, and broadened our search, accepting a broader variety of study designs in our inclusion criteria. (24) This decision was spurred both by the paucity of randomized, controlled trials (RCTs) in infants and a desire to capture any additional reliable and valid evidence presented by cohort and case-control studies.
METHODS
We performed a PubMed search using the search terms "Reglan neonate," "Reglan infant," "metoclopramide neonate," "metoclopramide infant," "gastroesophageal reflux medication," and "gastroesophageal reflux treatment." The search limits included English language, humans, age group "birth to 23 months," and publication dates 1980 to August 2005. Of the review articles identified by this search, the bibliographies of those from 1995-2005 with full-text available on-line were searched for additional articles that were missed by the PubMed search described above. Review articles were used only to screen for articles meeting the inclusion criteria for the study that were not identified by the PubMed search; reviews were not included in the analysis of the data.
We included only published articles in the systematic review. Study designs that met inclusion criteria were cohort studies, case-control studies, and controlled trials. We considered controls to be either a separate group of randomly assigned or nonrandomly assigned patients not receiving metoclopramide or individual patients acting as their own controls. Both blinded and nonblinded studies were included in the review. Abstracts, case reports, case series, and review articles were excluded from this analysis.
Outcomes included in the systematic review were limited to the efficacy, effectiveness, or toxicity of metoclopramide for reflux in infants. We defined efficacy as the therapeutic effect of the drug in a clinical trial and effectiveness as the benefit of the drug outside of a controlled research setting. We defined a toxicity of drug treatment as any unintended adverse consequence of the drug's use, such as dystonic reactions and irritability. Given the difficulty of quantifying GERD in a clinically and physiologically meaningful way, we accepted studies with outcomes that included clinical symptoms, pH-probe results, gastrointestinal motility, growth, or tolerance of feeding. In trials with treatment arms that included pharmacologic interventions other than metoclopramide, such as cisapride or bethanachol, we only considered the analyses comparing metoclopramide to nonintervention or placebo therapy.
We graded the level of evidence according to the scale for strength of overall evidence used by the US Preventive Services Task Force (USPSTF). (25) The quality and homogeneity of studies were assessed for suitability in a meta-analysis.
RESULTS
The PubMed search yielded 1284 articles. A search of 9 review article bibliographies (4,9,24,26-31) yielded 1 additional article. (14) By our consensus, 12 articles met the inclusion criteria. (10-18,32-34) Of these, 11 were intervention trials, (10-18,32,34)...
|
