A Review of Histamine-2 Receptor Antagonist and Proton Pump Inhibitor Therapy for Gastroesophageal Reflux Disease in Neonates and Infants.

Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are commonly used medications in neonates and infants for the treatment of gastroesophageal reflux disease (GERD), especially in neonatal intensive care units (NICUs). A literature review was conducted to evaluate the efficacy and safety of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) in preterm neonates, term neonates, and infants. A total of 27 studies were included in this review. Antacid medications in studies have consistently shown positive pharmacodynamic effects, including increasing gastric pH, reducing the reflux index, and reducing the number of acidic reflux events. The benefit found in placebo-controlled trials are limited exclusively to these surrogate outcomes. The actual clinically salient outcomes which H2RAs and PPIs are used for, such as reduction in GERD symptoms, especially irritability and improved feed tolerance and weight gain, have consistently shown no clinical benefit. H2RAs and PPIs appear to be extremely well tolerated by the neonatal and infant populations, which would mimic our experience with these medications in our unit. The available data from large, retrospective cohort and case-control studies paint a much more concerning picture regarding the potential for an increased risk in the development of allergies, anaphylactic reactions, necrotizing enterocolitis (NEC), other nosocomial infections, and lower respiratory tract infections. Given the risks associated with and lack of clinical effectiveness of both H2RAs and PPIs, use of these medications should be limited to specific clinical situations. Further studies are required to determine whether antacid pharmacologic therapy might benefit certain neonates and infants, such as those with complex medical issues.

Use of methadone for prevention of opioid withdrawal in critically ill children.

BACKGROUND: Opioids are commonly administered to critically ill children for analgesia and sedation, but many patients experience opioid withdrawal upon discontinuation. The authors' institution developed a protocol for using methadone to prevent opioid withdrawal in children who have received morphine by continuous IV infusion for 5 days or longer in the pediatric intensive care unit (PICU). OBJECTIVES: The primary objectives were to determine if opioids were tapered according to the protocol and to determine the conversion ratio for IV morphine to oral methadone that was used. Secondary objectives were to describe the methadone dosage used and the clinical outcomes, to evaluate adjustments to methadone dosing, and to report the incidence of adverse effects. METHODS: A retrospective analysis of charts was conducted for pediatric patients who had received morphine by continuous IV infusion for 5 days or longer followed by methadone in the PICU between May 2008 and August 2009. Validated scoring systems (the Withdrawal Assessment Tool and the State Behavioral Scale) were used to assess symptoms of withdrawal and degree of sedation, respectively. RESULTS: Forty-three patients were included in the study, with median age of 8 months (range 0.25-201 months). For 31 patients (72%), the protocol was not used, and there were no patients for whom the protocol was followed to completion. The median duration of weaning was 10 days (range 0-91 days). The conversion ratio for IV morphine to oral methadone was 1:0.78 for anticipated 5-day weaning and 1:0.98 for anticipated 10-day weaning. During the first 10 days of weaning, 18 patients (42%) experienced withdrawal symptoms. The methadone dose was increased for 11 (26%) of the 43 patients. Patients were sedated for a median of 1 day (range 0-9 days), were comfortable for a median of 6.5 days (range 1-64 days), and were agitated for a median of 2.5 days (range 0-23 days). Naloxone was required for 2 patients. CONCLUSIONS: The institution's methadone protocol was not followed consistently during the study period, and practices for transitioning from morphine by continuous IV infusion to methadone with tapering were also inconsistent. Further studies are needed to determine the optimal conversion ratio for morphine to methadone and the optimal tapering regimen to minimize withdrawal symptoms and adverse events.