Assessment of Pain in Newborns and Older Infants (Infant Pain Assessment Study = (iPAS))

Using Machine-learning Algorithms to Assess Acute Pain in Nonverbal Infants

Pain assessments in non-verbal, critically ill infants represent an important clinical challenge. Older children or adults can easily express their pain, but infants lack that capability. They frequently experience repetitive acute pain during routine ICU care, but their analgesic management flounders on the horns of a dilemma: (a) failure to treat infant pain leads to immediate clinical instability and potentially long-term physical, behavioral, and cognitive sequelae, vs. (b) strong analgesics may increase risks for medical complications and/or impaired brain growth. Bedside nurses currently assess pain using pain scores, before taking action to ameliorate pain. Pain scores increase nursing workload and provide subjective assessments, rather than objective data for evaluating infant pain. Consequently, infants exposed to skin-breaking procedures, surgery, or other painful conditions often receive variable and inconsistent pain management in the ICU. The investigators aim to develop a multimodal pain assessment system, using sensor fusion and novel machine learning algorithms to provide an objective measure of pain that is context-dependent and rater-independent. This will enhance the quality of pain management in ICUs and allow continuous pain monitoring in real-time.

Study Overview

• Status: Completed
• Conditions: Pain, Acute
• Intervention / Treatment: Other: Pain Measurement

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital Stanford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 9 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We will collect data from 30 study subjects in each of the following age groups:

• Preterm infants (34-37 weeks, postnatal age 3-30 days)
• Term newborns (37-42 weeks gestation, less than 1 month of age)
• Infants from 1-3 months age, and
• Older infants from 3-6 months age. A total of 120 subjects will be recruited before study closure.

Description

Inclusion Criteria:

• 1. All infants less than 6 months of corrected chronological age. 2. Infants admitted to the participating ICUs at LPCH (NICU, PICU, CVICU). 3. Require an acute painful procedure for routine clinical care.

Exclusion Criteria:

1. Newborns with birth trauma, intrapartum asphyxia (5-minute Apgar Score <4 or cord pH < 7.01), fetal growth restriction (birth weight < 5th percentile for gestation), congenital anomalies or metabolic disorders, or any kind of brain injury.
2. Newborns born to mothers with a history of heavy smoking or drug abuse (alcohol, cocaine, ketamine, heroin/other opiates) or psychiatric drugs used during this pregnancy.
3. Newborns and infants requiring positive pressure ventilation using a face mask (BiPAP) or endotracheal tube (conventional or high-frequency ventilators).
4. Newborns and infants receiving continuous infusions of opioid drugs (morphine, fentanyl, others) and nerve blocks or neuraxial analgesia affecting the site of the invasive procedure during the 24 hours prior to study entry. (Note: Infants receiving intermittent opioids or non-opioid analgesics (acetaminophen, ibuprofen, ketorolac, others) WILL NOT be excluded).
5. Newborns and infants with facial anomalies, injuries or other pathologies affecting the facial area.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Preterm infants; preterm neonates (34-37 weeks gestational age, n=15)	Other: Pain Measurement; Measurement of infant responses (behavioral and physiological) during a painful procedure.
Term infants; term newborns (37-42 weeks gestation, n=15)	Other: Pain Measurement; Measurement of infant responses (behavioral and physiological) during a painful procedure.
Small infants; 1-3 month-old infants (n=15)	Other: Pain Measurement; Measurement of infant responses (behavioral and physiological) during a painful procedure.
Older infants; 3-6 month-old infants (n=15)	Other: Pain Measurement; Measurement of infant responses (behavioral and physiological) during a painful procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Measurement (all infants)	Visual Analogue Scale (VAS) measures pain intensity based on observer assessment on a scale from 1 to 10, where higher values indicate more intense pain.	10 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Measurement	Facial Expressions specific for infant pain will be assessed, including nasolabial furrow and brow bulge. Presence or absence as well as the duration for each facial expression will be recorded during the painful procedure. These facial expressions were chosen from the Neonatal Facial Coding Scale (NFCS) and the Premature Infant Pain Profile (PIPP).	30 minutes
Pain Measurement (newborns 0-30 days)	Neonatal Pain, Agitation and Sedation Scale (N-PASS) measures level of sedation versus increasing pain or agitation in newborns. Scores range from -10 to +10, where negative scores denote increasing levels of sedation, zero indicates a neutral condition, and positive scores indicate increasing pain intensity and/or agitation.	5 minutes
Pain Measurement (newborns 0-30 days)	Premature Infant Pain Profile - Revised (PIPP-R) measures pain intensity in newborns, with scores ranging from 0 to 21, higher scores indicating greater pain (adjusted for prematurity and behavioral state).	8 minutes
Pain Measurement (infants 1-6 months)	Face, Legs, Activity, Cry, Consolability scale (FLACC scale) measures pain in children between the ages of 2 months and 7 years. The scale is scored in a range of 0-10 with 0 representing no pain and 10 indicating severe pain.	3 minutes

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Autonomous Healthcare, Inc.
• Investigators: Principal Investigator: Kanwaljeet S Anand, MBBS, D.Phil., Prof.

Publications and helpful links

General Publications

• Roue JM, Morag I, Haddad WM, Gholami B, Anand KJS. Using sensor-fusion and machine-learning algorithms to assess acute pain in non-verbal infants: a study protocol. BMJ Open. 2021 Jan 6;11(1):e039292. doi: 10.1136/bmjopen-2020-039292.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2017
• Primary Completion (Actual): April 29, 2021
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: October 24, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): June 8, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: pain; acute pain; infant-newborn; infant-premature
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: IRB-39076

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No data will be shared

Drug and device information, study documents

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