Clinical Science Research
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Background: Sedation is used during ECMO to prevent agitation. Analgesia is used to dampen pain perception as neonatal procedural pain related stress is associated with later altered neurodevelopment with poorer perceptual reasoning and visual perception. Common sedatives/analgesics used during ECMO are opiates and benzodiazepines. Studies have shown that lipophilic drugs such as Fentanyl and Midazolam are significantly sequestered in the circuit suggesting opportunities to improve delivery for pain.
Hypothesis and Methods: We hypothesized opportunities to improve sedation/analgesia drug treatment in ECMO patients. Using a retrospective analysis of all neonatal patients receiving ECMO between 2015-2020, we aimed to assess the relationship between sedative/analgesia type and dose and clinical complications. We identified patient demographics, medication type, dose used, days to wean, length of hospital stay, mortality, medical complications at discharge and MRI results.
Results: 49 patients were included, mean gestational age 37.6 wks ±3.6. Seventeen (35%) infants died. Race was not associated with mortality. All patients received Fentanyl and Midazolam with one patient who also received Morphine infusion. Fentanyl and Midazolam dose during ECMO was associated with risk for oxygen at discharge 296 vs 517 mcg/kg/days for Fentanyl (p=0.04), and 358 vs 2598 mcg/kg/days for Midazolam (p=0.002) as well as need for feeding tube at discharge 272 vs 420 mcg/kg/days for Fentanyl (p=0.049) and 1.03 vs 1.60 mg/kg/days for Midazolam(p=0.04). Risk for abnormal MRI was increased with Fentanyl ECMO dose exposure (p=0.016). Male gender was associated with greater fentanyl dose exposure by 27% (p=0.038).
Conclusion: Fentanyl and Midazolam increased dose exposure was associated with increased risk for later neurological clinical complications in infants undergoing ECMO. Further studies are needed to assess serum drug concentrations in ECMO patients to better understand development of drug tolerance, circuit sequestration and dose exposure to adjust the therapeutic range of sedation and analgesia use.
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VCU School of Medicine GME Resident and Fellow Research Day Posters