Peitz, Gregory

Fentanyl is commonly used in critically ill patients receiving extracorporeal membrane oxygenation (ECMO). Fentanyl’s lipophilicity and protein binding may contribute to a sequestration of the drug in the ECMO circuit. Hydromorphone lacks these characteristics potentially leading to a more predictable drug delivery and improved pain and sedation management among ECMO patients. This study compared hydromorphone to fentanyl in patients receiving ECMO. This retrospective study included adult patients receiving ECMO for ≥48 hours. Patients were excluded if they required neuromuscular blockade, received both fentanyl and hydromorphone during therapy, or had opioid use before hospitalization. Baseline characteristics included patient demographics, ECMO indication and settings, and details regarding mechanical ventilation. The primary outcome was opioid requirements at 48 hours post cannulation described in morphine milligram equivalent (MME). Secondary endpoints included 24-hour opioid requirements, concurrent sedative use, and differences in pain and sedation scores. No differences were noted between the patients receiving fentanyl (n = 32) or hydromorphone (n = 20). Patients receiving hydromorphone required lower MME compared to fentanyl at 24 hours (88 [37–121] vs. 131 [137–227], p < 0.01) and 48 hours (168 [80–281] vs. 325 [270–449], p < 0.01). The proportion of within-goal pain and sedation scores between groups was similar at 24 and 48 hours. Sedative requirements did not differ between the groups. Patients receiving hydromorphone required less MME compared to fentanyl without any differences in sedative requirements, or agitation-sedation scores at 48 hours. Prospective studies should be completed to validate these findings.

Objective: To summarize the role of pharmacotherapy in the management of phenylketonuria (PKU) and to review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile of sapropterin for this indication. Data Sources: A literature search was conducted using MEDLINE (1966–May 2009), International Pharmaceutical Abstracts (1970–May 2009), and Cochrane database (2008) for the following key words: sapropterin, tetrahydrobiopterin, phenylketonurias, and phenylalanine. Study Selection and Data Extraction: English-language studies involving humans examining the role of tetrahydrobiopterin (BH4) in the management of PKU were reviewed to evaluate the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile for sapropterin. All Phase 2 and 3 randomized controlled trials assessing the safety and efficacy of sapropterin were included in this literature evaluation. Data Synthesis: Sapropterin represents the only Food and Drug Administration–approved medication for BH4-responsive PKU, marking an important advance in the treatment of this condition. Among individuals with hyperphenylalaninemia and some residual phenylalanine hydroxylase function, sapropterin can enhance activity of this enzyme to decrease serum phenylalanine concentrations. Sapropterin has been compared with placebo in one Phase 2 and one Phase 3 clinical trial, demonstrating significantly better response rates. Based on available studies, this agent appears to be safe and well tolerated, with adverse event rates similar to those of placebo. However, additional studies are warranted to assess the long-term safety and efficacy of sapropterin therapy. Conclusions: Sapropterin offers a promising therapeutic option for select individuals with BH4-responsive PKU, although long-term data are limited evaluating its safety and efficacy in traditional clinical practice settings. When considering sapropterin therapy, clinicians must consider factors such as cost and patient adherence to drug therapy and/or diet.