Abdominal Pain, Isolated Extremity Fracture, Pain, Pediatrics
Conditions
Keywords
Ketamine, Morphine, Pediatric, Children, Sub-dissociative, Opioid-sparing, Emergency medicine, Emergency care, Emergency department, Post-traumatic stress, Anxiety, Depression, Abdominal pain, Fracture, Analgesia
Brief summary
Pain is common in children presenting to the emergency department but is frequently undertreated, leading to both short- and long-term consequences. Morphine is the standard treatment for children with moderate to severe acute pain, but its use is associated with serious side effects and caregiver and clinician concerns related to opioid administration. The investigators aim to determine if sub-dissociative ketamine is non-inferior to morphine for treating acute pain and a preferable alternative for treating acute pain in children because of its more favorable side effect profile and potential long-term benefits related to pain-related function, analgesic use/misuse, and mental and behavioral health outcomes.
Detailed description
Aim 1: To determine if IV sub-dissociative ketamine is non-inferior to IV morphine for decreasing pain intensity in children presenting to an ED with acute pain. The investigators hypothesize that IV sub-dissociative ketamine is non-inferior to IV morphine for decreasing pain intensity in children with acute abdominal pain or an extremity fracture. Aim 2: To compare the rate of acute (\<2 hours) adverse events, including cardiopulmonary adverse events requiring an intervention, associated with IV sub-dissociative ketamine and IV morphine. The investigators hypothesize that there is a smaller proportion of cardiopulmonary adverse events requiring an intervention associated with IV sub-dissociative ketamine compared to IV morphine. Aim 3: To determine the relationship between ketamine and long-term sequelae of acute pain. The investigators hypothesize that children who receive ketamine will have better levels of pain-related function during the first week following ED presentation and will have greater odds of experiencing more favorable post-traumatic stress, anxiety and depression outcomes 1-6 months after ED presentation compared to children who received IV morphine.
Interventions
DRUGKetamine hydrochloride
Sub-dissociative ketamine, IV
Morphine, IV
Sponsors
Columbia University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Non-inferiority trial design
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Age 6 to \< 18 years old 2. Chief complaint includes abdominal pain OR isolated long-bone extremity fracture (suspected or proven) 3. Self-reported pain score of ≥ 6/10 4. Requires IV morphine for analgesia as determined by the treating physician
Exclusion criteria
1. Weighs more than 81.9 kg 2. Known allergy/contraindication to morphine or ketamine 3. Antecedent receipt of ketamine related to presenting complaint 4. Inability to use self-report measures of pain or questionnaires 5. Chronic disease associated with pain 6. Chronic pain conditions requiring use of opioids as an outpatient 7. Abnormal vital signs at baseline, defined as oxygen saturation \<92% and/or low respiratory rate and/or low heart rate and/or low blood pressure per age 8. Altered mental state (e.g., GCS \< 14 or clinical intoxication) 9. Known history of schizophrenia, liver or kidney problems, or osteogenesis imperfecta 10. Concern for open fracture, neurovascular compromise, or compartment syndrome 11. Injuries in addition to the extremity injury (e.g., head, neck, abdomen) 12. Known or reported pregnancy 13. Patients who are breastfeeding 14. Patient or parent/guardian does not speak English or Spanish 15. Patient previously enrolled in this study 16. Known significant or uncontrolled cardiovascular disease 17. Known increased intracranial pressure and/or elevated intraocular pressure 18. Currently taking or having used a monoamine oxidase inhibitor within 14 days 19. Wards of state, foster children, or children in custody
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain intensity | Up to 240 minutes after completion of study drug administration or until a terminal event occurs | Self-reported pain intensity measured using the Verbal Numerical Rating Scale (VNRS). Scored from 0 to 10. A higher score indicates a worse outcome. |
| Cardiopulmonary adverse events requiring an intervention | Up to 120 minutes after completion of study drug administration or until a terminal event occurs | Cardiopulmonary adverse events (e.g., hypoxia, respiratory depression, hypotension) requiring an intervention (e.g., isotonic fluid bolus; vasopressor; chest compression; naloxone; supplemental oxygen; non-invasive positive pressure ventilation; bag-valve-mask ventilation; tracheal intubation) |
| Pain-related function | Days 1, 2,3, and 7 after discharge. | Pain intensity and related functional limitations due to pain, measured using the Parents' Postoperative Pain Measure (PPPM). Scored from 0 to 10. A higher score indicates a worse outcome. |
| Post-traumatic stress | Baseline (at time of enrollment) and days 7, 30, 90 and 180 after discharge. | Stress related to the pain experienced measured using the University of California Los Angeles Post-Traumatic Stress Disorder (UCLA PTSD). Scored from 0 to 80. A higher score indicates a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Desire of rescue analgesia | Up to 120 minutes after completion of study drug administration or until a terminal event occurs | Number of participants who indicated that they desired a rescue analgesic |
| Desire for same analgesic | At 240 minutes after completion of study drug administration or when a terminal event occurs | Number of participants who would want the same analgesic (i.e., study medication) again in the future. |
| Depth of sedation | Up to 240 minutes after completion of study drug administration or until a terminal event occurs | Depth of sedation measured using the University of Michigan Sedation Scale (UMSS). Scored from 0 to 4. 0 is deepest level of sedation (unarousable), 4 is awake and alert. |
| Adverse events, non-cardiopulmonary | Up to 120 minutes after completion of study drug administration or until a terminal event occurs | Adverse events that are non-cardiopulmonary and can include (but are not limited to) opioid-related adverse events or those as measured using the Side Effects Rating Scale of Dissociative Anesthetics (SERSDA). |
| Analgesic/opioid use after discharge | Days 1, 2, 3, 7, 30, 90, and 180 after discharge | Name, dose and duration of analgesics and/or opioids used to calculate total days of use during the elapsed time since last assessment |
| Missed school or work | Day 7 after discharge | Days of missed school or work related to the chief complaint. |
| Return visit | Day 7, 30, 90, 180 after discharge | Number of return visits related to the chief complaint, which can include (but not limited to) return visits to the emergency department or primary care physician |
| Anxiety | Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge | PROMIS Anxiety 8a. Scored from 8 to 40. A higher score indicates a worse outcome. |
| Depression | Baseline (at time of enrollment) and days 7, 30, 90, and 180 after discharge | Patient-Reported Outcomes Measurement Information System (PROMIS). Scored from 8 to 40. A higher score indicates a worse outcome. |
| Substance use | Baseline (at time of enrollment) and day 30 after discharge | National Institute on Drug Abuse (NIDA) modified assist tool. Scored from 0 to 360. A higher score indicates a worse outcome. |
Countries
United States
Contacts
CONTACTDaniel S Tsze, MD, MPH
CONTACTAmy L Drendel, DO, MS
PRINCIPAL_INVESTIGATORDaniel S Tsze, MD, MPH
Columbia University
PRINCIPAL_INVESTIGATORAmy L Drendel, DO, MS
Medical College of Wisconsin
Outcome results
None listed