Pain Assessment During Less-Invasive-Surfactant-Administration (PALISA)

The PALISA Study - Pain Assessment During Less-Invasive-Surfactant-Administration

Primary aims of the study are to evaluate the feasibility of Skin conductance (SC) measurements and its correlation to Neonatal Pain and Distress Scale (N-PASS) - scores during the Less-Invasive-Surfactant-Administration (LISA)-procedure in preterm infants. Secondary aims are to evaluate the effect of LISA on the general stress-level in preterm infants with respiratory distress syndrome.

The assessment of pain and stress with SC measurement in addition to the subjective assessment with N-PASS may provide more conclusive data on the sensation of pain or stress during the LISA procedure and therefore the necessity of analgosedation. Therefore, this study might help to identify those infants in need for analgosedation, which would allow an individualized approach in the future.

Study Overview

• Status: Completed
• Conditions: Pain; Stress; Infant, Premature, Diseases; Respiratory Distress Syndrome; Surfactant Deficiency Syndrome Neonatal
• Intervention / Treatment: Other: Skin Conductance (SC) Measurement; Other: Video Recording

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, CH-8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All preterm infants with ≥27 0/7 weeks of gestation at birth who meet the inclusion criteria and who do not fulfill the exclusion criteria

Description

Inclusion Criteria:

• Preterm infants ≥27 0/7 weeks of gestation at birth
• Need for surfactant therapy via LISA according to the local standard operating procedure
• ≥27 0/7 weeks of gestation,
• within first 48 hours of life
• FiO2 ≥0.30 to maintain SpO2 ≥90% for 15 min,
• non-invasive respiratory support with PEEP 6-8 cmH2O
• consent of attending NICU staff for videorecording

Exclusion Criteria:

• Primary intubation in the delivery room
• Severe congenital malformation or other conditions requiring immediate endotracheal intubation
• Insufficient language skills (German or English) of the parents to understand and consent the participation in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Preterm infants with minimal gestational age of 27 weeks requiring LISA; LISA will be preformed according to our local standard protocol while measuring skin conductance via a specific monitor. At the same time a video is recorded for later unblinded and blinded N-PASS assessment.

Other: Skin Conductance (SC) Measurement; SC will be measured using a specific monitor and three self-adhesive electrodes on one foot of the infant (one plantar and two on the ankles). Peaks per second (the rate of firing in the sympathetic nerves), average amplitude (mean peaks) and area under curve (forcefulness of sympathetic nerve firing) will be automatically analyzed. Corresponding data will be transferred to a separate tablet computer via bluetooth.; Other: Video Recording; The video recording for later N-PASS assessment will be done by a camera fixed above the incubator / resuscitation unit, not interfering with the LISA procedure. The video will show the full body of the newborn as well as the hands / forearms of the treating clinical team with the awareness and oral consent of the treating team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median peaks per second at prespecified time-points adjusted for median peaks per second at baseline	The prespecified time-points are: baseline: before starting of interventions (2 minutes recording without any intervention);; insertion of nasopharyngeal tube;; insertion of laryngoscope for visualization of the vocal cords;; insertion of LISA catheter; administration of surfactant; removal of catheter; 5 minutes after removal of catheter (2 minutes recording without any intervention); 1 hour (±10 minutes) after LISA (2 minutes recording without any intervention)	2 minutes before LISA, during LISA, 1 hour (±10 minutes) after LISA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute number of apneas	Absolute number of apneas requiring non-invasive pressure ventilation or increase of peak inspiratory pressure or frequency during the LISA procedure	During LISA procedure
Absolute number of desaturations	Absolute number of decreasing SpO2 requiring increase of FiO2 during the LISA procedure	During LISA procedure
Absolute number of bradycardia	Absolute number of bradycardia (<100/min) during the LISA procedure	During LISA procedure
Absolute number of arterial hypotension	Absolute number of arterial hypotension with mean blood pressure lower than gestational age during the LISA procedure	During LISA procedure
Absolute number of blunt surfactant reflux	Absolute number of blunt surfactant reflux seen in mouth or nose without laryngoscopy during the LISA procedure	During LISA procedure
Difference in maximum peaks per second before and after apnea	Difference in maximum peaks per second before and after apnea requiring non-invasive pressure ventilation or increase of peak inspiratory pressure or frequency during the LISA procedure	During LISA procedure
Difference in median peaks per second during 20-second interval before and after apnea	Difference in median peaks per second during 20-second interval before and after apnea requiring non-invasive pressure ventilation or increase of peak inspiratory pressure or frequency during the LISA procedure	During LISA procedure
Difference in maximum peaks per second before and after desaturation	Difference in maximum peaks per second before and after decreasing SpO2 requiring increase of FiO2 during the LISA procedure	During LISA procedure
Difference in median peaks per second during 20-second interval before and after desaturation	Difference in median peaks per second during 20-second interval before and after decreasing SpO2 requiring increase of FiO2 during the LISA procedure	During LISA procedure
Difference in maximum peaks per second before and after bradycardia	Difference in maximum peaks per second before and after bradycardia (<100/min) during the LISA procedure	During LISA procedure
Difference in median peaks per second during 20-second interval before and after bradycardia	Difference in median peaks per second during 20-second interval before and after bradycardia (<100/min) during the LISA procedure	During LISA procedure
Difference in maximum peaks per second before and after arterial hypotension	Difference in maximum peaks per second before and after arterial hypotension with mean blood pressure lower than gestational age during the LISA procedure	During LISA procedure
Difference in median peaks per second during 20-second interval before and after arterial hypotension	Difference in median peaks per second during 20-second interval before and after arterial hypotension with mean blood pressure lower than gestational age during the LISA procedure	During LISA procedure
Difference in maximum peaks per second before and after blunt surfactant reflux	Difference in maximum peaks per second before and after blunt surfactant reflux seen in mouth or nose without laryngoscopy during the LISA procedure	During LISA procedure
Difference in median peaks per second during 20-second interval before and after blunt surfactant reflux	Difference in median peaks per second during 20-second interval before and after blunt surfactant reflux seen in mouth or nose without laryngoscopy during the LISA procedure	During LISA procedure
Difference in heart-rate between baseline and prespecified time-points as listed above.	Difference in heart-rate between baseline and prespecified time-points as listed above 2 minutes before LISA, during LISA and 1 hour (±10 minutes) after LISA	2 minutes before LISA, during LISA, 1 hour (±10 minutes) after LISA
Difference in oxygen saturation between baseline and prespecified time-points as listed above.	Difference in oxygen saturation between baseline and prespecified time-points as listed above 2 minutes before LISA, during LISA and 1 hour (±10 minutes) after LISA	2 minutes before LISA, during LISA, 1 hour (±10 minutes) after LISA
Difference in SpO2/FiO2-ratio between baseline and prespecified time-points as listed above.	Difference in SpO2/FiO2-ratio between baseline and prespecified time-points as listed above 2 minutes before LISA, during LISA and 1 hour (±10 minutes) after LISA	2 minutes before LISA, during LISA, 1 hour (±10 minutes) after LISA
Difference of SpO2/FiO2-ratio compared to skin conductance peaks per second	Difference of SpO2/FiO2-ratio at baseline, 5 minutes after removal of catheter and 60 minutes after LISA compared to skin conductance peaks per second (median peaks per second of 2 minute intervals).	2 minutes before LISA, 5 minutes after removal of catheter, 60 Minutes after LISA
LISA failure	Incidence of LISA failure defined as intubation or repeated LISA within 24 hours	Within 24 hours after LISA
Intubation <72 hours after the LISA procedure	Incidence of intubation within <72 hours after the LISA procedure	Within 72 hours after LISA
Air-leaks <72 hours after the LISA procedure	Incidence of air-leaks within <72 hours after the LISA procedure	Within 72 hours after LISA
Incidence of intraventricular hemorrhage	Incidence of intraventricular hemorrhage at first ultrasound scan after 72 hours	72 hours after LISA
Median Neonatal Pain, Agitation and Sedation Scale (N-PASS) at prespecified time-points, adjusted for median N-PASS at baseline	The N-PASS serves as a tool for evaluating pain and sedation levels in newborns. In the context of this study, the focus is solely on assessing pain. Five criteria, including crying, behavior, facial expression, extremity tone and vital signs, are rated on a scale of 0 to 2 points each. These individual scores are then added up to calculate a total pain score, which falls within the range of 0 to 10. A higher total score correlates with a higher level of perceived pain. The prespecified time-points, at which the N-PASS will be assessed, are: baseline: before starting of interventions; during insertion of laryngoscope for visualization of the vocal cords; administration of surfactant; 5 minutes after removal of catheter; 1 hour (±10 minutes) after LISA	2 minutes before LISA, during LISA, 1 hour (±10 minutes) after LISA

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Study Chair: Dirk Bassler, MD, Newborn Research, Department of Neonatology, University Hospital and University of Zurich

Publications and helpful links

General Publications

• Storm H. Changes in skin conductance as a tool to monitor nociceptive stimulation and pain. Curr Opin Anaesthesiol. 2008 Dec;21(6):796-804. doi: 10.1097/ACO.0b013e3283183fe4.
• Hummel P, Puchalski M, Creech SD, Weiss MG. Clinical reliability and validity of the N-PASS: neonatal pain, agitation and sedation scale with prolonged pain. J Perinatol. 2008 Jan;28(1):55-60. doi: 10.1038/sj.jp.7211861. Epub 2007 Oct 25.
• Hummel P, Lawlor-Klean P, Weiss MG. Validity and reliability of the N-PASS assessment tool with acute pain. J Perinatol. 2010 Jul;30(7):474-8. doi: 10.1038/jp.2009.185. Epub 2009 Nov 19.
• Storm H. Skin conductance and the stress response from heel stick in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2000 Sep;83(2):F143-7. doi: 10.1136/fn.83.2.f143.
• Peterson J, den Boer MC, Roehr CC. To Sedate or Not to Sedate for Less Invasive Surfactant Administration: An Ethical Approach. Neonatology. 2021;118(6):639-646. doi: 10.1159/000519283. Epub 2021 Oct 8.
• Tribolet S, Hennuy N, Snyers D, Lefebvre C, Rigo V. Analgosedation before Less-Invasive Surfactant Administration: A Systematic Review. Neonatology. 2022;119(2):137-150. doi: 10.1159/000521553. Epub 2022 Feb 4.
• Munsters J, Wallstrom L, Agren J, Norsted T, Sindelar R. Skin conductance measurements as pain assessment in newborn infants born at 22-27 weeks gestational age at different postnatal age. Early Hum Dev. 2012 Jan;88(1):21-6. doi: 10.1016/j.earlhumdev.2011.06.010. Epub 2011 Jul 20.
• Morgan ME, Kukora S, Nemshak M, Shuman CJ. Neonatal Pain, Agitation, and Sedation Scale's use, reliability, and validity: a systematic review. J Perinatol. 2020 Dec;40(12):1753-1763. doi: 10.1038/s41372-020-00840-7. Epub 2020 Oct 2.
• Dirler C, Boos V, Bassler D, Benke-Bruderer S, Held U, Ruegger CM, Muehlbacher T. Pain Assessment During Less Invasive Surfactant Administration Using Skin Conductance: A Prospective Cohort Study. Pediatr Res. 2025 Dec 22. doi: 10.1038/s41390-025-04703-9. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2023
• Primary Completion (Actual): June 14, 2024
• Study Completion (Actual): June 17, 2024

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: November 20, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Analgosedation; Neonatal Pain and Sedation Scale; Skin Conductance; Less-Invasive-Surfactant-Administration; General stress-level
• Additional Relevant MeSH Terms: Neurologic Manifestations; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Respiratory Distress Syndrome; Pulmonary Atelectasis; Infant, Premature, Diseases; Investigative Techniques; Technology, Industry, and Agriculture; Technology; Tape Recording; Audiovisual Aids; Educational Technology; Television; Weights and Measures; Videotape Recording
• Other Study ID Numbers: PALISA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No