In the evolving landscape of neonatal care, pain management during minimally invasive surfactant therapy (LISA) remains a critical concern. Recent research spearheaded by Breindahl and colleagues has embarked on a remarkable journey to explore whether non-pharmacological comfort care can effectively replace fentanyl administration during LISA procedures. The study, titled “Can non-pharmacological comfort care replace fentanyl in LISA? The NONA-LISA feasibility study,” published in Pediatric Research (2025), challenges conventional approaches by investigating comfort measures that avoid pharmacological intervention, proposing a potentially transformative shift in neonatal pain management.
LISA is a frontline technique for administering surfactant to preterm infants with respiratory distress syndrome, aiming to improve lung compliance without the need for mechanical ventilation. However, despite its minimally invasive nature, the procedure is often associated with pain and distress, which traditionally has been managed through pharmacological agents like fentanyl. While effective, opioids such as fentanyl carry notable risks including respiratory depression, delayed gut motility, and potential neurodevelopmental consequences. This context sets the stage for exploring alternative strategies that prioritize safety and efficacy without exposing these vulnerable neonates to opioid-related side effects.
The NONA-LISA study took a pioneering approach by rigorously evaluating non-pharmacological comfort care methods during the surfactant administration process. These interventions encompassed a suite of evidence-based comfort techniques such as facilitated tucking, oral sucrose, non-nutritive sucking, and gentle containment, all designed to soothe infants and mitigate procedural pain. By focusing on these sensory and behavioral methods, the research team sought to determine if sufficient analgesia could be achieved to forgo opioid use altogether.
One of the fundamental challenges in neonatal pain research lies in accurately assessing pain, given that infants cannot verbally communicate their discomfort. The study utilized validated neonatal pain scales, meticulously documenting physiological parameters such as heart rate, oxygen saturation, and facial expressions, alongside behavioral cues to quantify the infants’ pain response. These comprehensive assessments allowed the researchers to compare efficacy between fentanyl administration and non-pharmacological strategies under controlled clinical conditions.
The results of the NONA-LISA feasibility study are striking. Data suggested that non-pharmacological comfort care significantly attenuated signs of pain and distress during the LISA procedure. Infants who received these comfort interventions exhibited stable vital signs and fewer pain manifestations compared to historical controls treated with fentanyl. These findings challenge the long-standing reliance on opioid analgesics in neonatal intensive care units and support a paradigm shift towards gentler, less invasive pain management techniques.
Beyond safety, the implications of minimizing opioid exposure are profound. Neonates, particularly preterm infants, are susceptible to cumulative drug effects that may interfere with brain development and long-term neurocognitive outcomes. By employing non-pharmacological comfort care, clinicians can potentially mitigate these risks, fostering healthier developmental trajectories. Furthermore, reducing pharmacological interventions streamlines clinical workflows, potentially reducing hospital stay durations and associated healthcare costs.
Despite the encouraging results, the study acknowledges the need for larger, randomized controlled trials to validate these findings further and explore the nuanced balance between comfort care and the necessity of pharmacological support in more complex cases. The feasibility focus of this initial research lays the groundwork for future studies that could definitively reshape neonatal pain management guidelines, emphasizing versatility and patient-centered approaches.
Importantly, the study also highlights the role of multidisciplinary collaboration in advancing neonatal care. The integration of neonatologists, nurses, pain specialists, and developmental psychologists was crucial in designing and implementing the non-pharmacological interventions effectively. This holistic perspective recognizes that procedural pain is not just a physical sensation but involves emotional and neurological dimensions that can be addressed through informed caregiving techniques.
Moreover, the ethical considerations underpinning the study cannot be overstated. Ensuring that neonates receive adequate pain relief while minimizing potential harms aligns with the principles of beneficence and non-maleficence central to pediatric healthcare. Transitioning away from opioid reliance also responds to the growing societal concerns regarding opioid use and the imperative to safeguard the most vulnerable populations from drug-related complications.
The technology and equipment used in the NONA-LISA study adhered to current clinical standards, reinforcing that enhanced neonatal comfort does not require sophisticated or cost-prohibitive devices. Instead, the study underscores the potency of human touch, soothing environments, and well-established sensory interventions that can be feasibly implemented across diverse neonatal intensive care settings globally.
Furthermore, the study’s timing is particularly relevant amid the increasing emphasis on family-centered care models. Non-pharmacological comfort interventions align seamlessly with involving parents in the care process, enabling them to participate actively in comforting and supporting their infants during procedures. Such involvement not only benefits the neonate but also strengthens parental bonding and empowerment, which are critical in the stressful NICU environment.
The NONA-LISA study also prompts deeper inquiry into the neurobiological mechanisms through which non-pharmacological interventions exert analgesic effects. Researchers postulate that gentle touch, sucrose administration, and containment may activate endogenous opioid pathways or modulate stress responses via parasympathetic nervous system engagement. Elucidating these pathways could open avenues for developing novel analgesic strategies that harness natural physiological processes.
In conclusion, the work of Breindahl et al. marks a significant advancement in neonatal care by convincingly demonstrating that non-pharmacological comfort care can be a viable alternative to fentanyl in LISA procedures. While larger studies are warranted to establish definitive protocols, the findings herald a shift toward safer, developmentally supportive pain management approaches. This evolution not only promises to enhance the clinical outcomes for infants but also aligns with broader healthcare goals of minimizing medication exposure and optimizing patient comfort through empathetic, evidence-based care strategies.
As neonatal intensive care continues to progress, integrating this knowledge into practice will require comprehensive education and training for healthcare professionals. Empowering care teams with the skills to deliver effective non-pharmacological comfort interventions is essential for translating research insights into real-world benefits. The potential to transform painful procedures into more humane experiences for preterm infants serves as a powerful impetus for continued innovation and compassion in neonatal medicine.
Looking forward, the implications of the NONA-LISA feasibility study extend beyond surfactant administration. The principles of non-pharmacological comfort care could be adapted to other painful procedures common in neonatal units, including blood sampling, line insertion, and mechanically assisted respiratory support. Such broad applicability underscores the profound impact that empathetic, low-risk interventions can have across the spectrum of neonatal care.
In essence, the NONA-LISA study epitomizes a new era in pediatric research where innovation meets compassion, advocating for care practices that prioritize the unique vulnerabilities and strengths of neonates. By challenging entrenched norms and offering viable alternatives, this research paves the way for gentler, safer, and more effective neonatal pain management strategies that could redefine standards worldwide.
Subject of Research: Pain management in neonates during minimally invasive surfactant therapy (LISA), focusing on the comparison between non-pharmacological comfort care and fentanyl use.
Article Title: Can non-pharmacological comfort care replace fentanyl in LISA? The NONA-LISA feasibility study.
Article References:
Breindahl, N., Henriksen, T.B., Heiring, C. et al. Can non-pharmacological comfort care replace fentanyl in LISA? The NONA-LISA feasibility study. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04310-8
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