Pain, Pain, Postoperative
Conditions
Keywords
acetaminophen, pain, neonate, infant, tylenol, paracetamol, postoperative, surgery
Brief summary
The goal of this pilot randomized clinical trial is to determine the effect of the addition of IV acetaminophen to opioid-based pain regimes for infants admitted to the neonatal intensive care unit (NICU) after surgery. This is a pilot trial; the main goals are to make sure our study methods work before performing a larger study. The main clinical aims are: 1. Determine if adding IV acetaminophen reduces pain 2. Determine if adding IV acetaminophen reduces opioid use 3. Determine if adding IV acetaminophen reduces complications Participants will be randomized to two groups: Comparator: Fentanyl and IV acetaminophen Control: Fentanyl and placebo Patients will receive either IV acetaminophen or placebo at regular intervals for seven days after surgery. Patients will be followed daily during that period. Charts will be reviewed at 90-days for final outcomes.
Detailed description
Purpose: Opioid use in neonates is associated with short and long-term adverse events. Multi-modal pain control offers the ability to control pain while reducing opioid exposure. This topic has been relatively unexamined in preterm and term neonates. Specifically, this trial aims to evaluate the effect of adding IV acetaminophen to standard opioid-based pain regimes in neonates in the neonatal intensive care unit (NICU) undergoing major abdominal and thoracic surgery. Objectives: The primary aim of the proposed study is to determine the feasibility and cost of conducting a multicenter, randomized control trial to compare the efficacy of IV acetaminophen and fentanyl, to fentanyl and saline placebo, in terms of reduction of postoperative pain, opioid use, adverse events. The primary outcome is feasibility; secondarily, efficacy and safety will be assessed. Design: This single-center, parallel-arm, placebo-controlled, fully blinded, randomized controlled external feasibility trial will enroll patients admitted in the neonatal intensive care unit (NICU) who have undergone major, thoracic, or abdominal surgery. Patients will be randomized 1:1, with parallel allocation to receive acetaminophen and fentanyl or fentanyl and saline placebo. All study staff, clinical staff and guardians will be blinded. As this is a pilot study, no sample size will be calculated, however; we aim to enroll 60 patients. A sample size calculation will be completed for the full RCT if it is deemed feasible from the results of this study. Patients will be followed for the day of surgery and the following 7 postoperative days (192 hours) and have their charts reviewed at 90 days. Impact: The results of this study will be used to determine the feasibility of conducting a multi-center RCT to assess the effect of IV acetaminophen on fentanyl infusions in postoperative neonatal patients. The effect of IV acetaminophen for postoperative pain in preterm neonates has yet to be studied, this trial would generate novel insights into its efficacy. The prolonged follow-up period would also provide novel insights into recovery throughout the entire perioperative period.
Interventions
DRUGAcetaminophen
IV acetaminophen will be added to standard of care opioid based pain regimes.
DRUGPlacebo
In control group placebo will be added to standard of care opioid based pain regimes.
Sponsors
McMaster Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
IV acetaminophen and saline appear identical in solution. They will be administered at identical rates. Care providers, participants' parents, investigators, outcomes assessors, and statisticians will remain blinded.
Intervention model description
Patients will be randomized to the control or comparator group. There will be 60 patients enrolled, with 30 patients per arm.
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
Healthy volunteers
No
Inclusion criteria
1. Neonates, admitted to McMaster Children's Hospital NICU 2. Has had major open, thoracic or abdominal surgery (see appendix 1, table 6). 3. Informed consent obtained from guardian(s)
Exclusion criteria
1. Hepatic dysfunction * AST, ALT or Bilirubin \> 3x upper limit of normal * INR ≥ 3.0 or PT greater than 20s regardless of vitamin K administration 2. Renal dysfunction * Increase in serum creatinine ≥ 2x baseline (baseline: lowest value in first 5 days of hospitalization) * Urine output \< 0.5 mL/kg/h for ≥ 12h 3. Allergy or intolerance to acetaminophen or fentanyl 4. Acetaminophen administration within 24 hours of the end of surgery 5. Nerve blocks or epidurals 6. Refusal or withdrawal of consent 7. Enrolment in another competing trial 8. No later than 12 hours after the end of surgery 9. 12 months post gestational age or greater in age 10. Birthweight greater or equal to 2,500g. 11. Discharged from the McMaster NICU
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment rate | through study completion, an average of 1.5 years | Mean number of patients randomized per month |
| Blinding index | 7 days | Responses of nurse's physician's, and research staff's guess of group assignment (control vs treatment) compared to actual group assignment |
| Medication compliance | 7 days | Number of patients who received at least 80% of doses of study drugs at the correct dose and interval |
| Follow up rate | 90 days | Number of patients followed in completion from postoperative day 0 to 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total fentanyl consumption | 7 days | Daily fentanyl consumption will be added together for the entire study period to determine the total amount of fentanyl consumed in mcg/kg. |
| Postoperative Pain | every 6 hours for entire study period (7 days after surgery) | Measured by the N-PASS Pain Scale as units on the scale (scale ranges from 0-10) |
| Daily fentanyl consumption | daily for 7 days | Fentanyl consumption will be recorded for each patient for each 24-hour period in the study period. Will be recorded in mcg/kg. |
| Daily Consumption of other analgesics | daily for 7 days | Consumption of other analgesics will be recorded for each patient for each 24-hour period in the study period. Will be recorded in mg or mcg /kg. |
| Total consumption of other analgesics | 7 days | Daily consumption of other analgesics will be added together for the entire study period to determine the total amount of fentanyl consumed in mg or mcg/kg. |
| Invasive ventilation | 90 days | Length of time requiring intubation |
| Non-invasive ventilation | 90 days | Length of time requiring CPAP, BiPAP, or supplemental oxygen |
| Enteral feeds | 90 days | Time to first enteral feeds and time to full enteral feeds (using NICU's calculated goal feed) |
| Bowel movement | 90 days | Time to first bowel movement |
| Glycerin suppository use | 90 days | Number of patients requiring one or more glycerin suppositories |
| Length of stay | 90 days | with discharge destination |
Other
| Measure | Time frame | Description |
|---|---|---|
| Apnea | 7 days | Number of patients with oxygen saturation less than 94% or RR less than 20 breaths/min for more than 30 seconds |
| Bradycardia | 7 days | Number of patients with HR less than 100 for more than 30 seconds |
| Hypotension | 7 days | Number of patients with SBP less than 60, or requiring vasoactive medication |
| Foley catheterization | 7 days | Number of patients, mean duration |
| Feeding intolerance | 7 days | Number of patients: feeds stopped or decreased due to vomit/increased gastric output, or if diagnosed by the treating team |
| Hepatic injury | 90 days | Number of patients with hepatic injury as defined in the protocol |
| Mortality | 90 days | all cause mortality |
| Reintubation | 90 days | Number of patients |
| NG/Vygone | 90 days | Number of patients, mean duration |
| Vomiting | 7 days | Number of patients with ≥ 1 episode of vomiting documented |
| Naloxone administration | 7 days | Number of patients |
Countries
Canada
Contacts
Primary ContactVictoria Archer, MD
Outcome results
None listed