Czarnecki 2020.

Study characteristics
Methods	Study design: Randomized clinical trial Study grouping: Morphine parent/nurse‐controlled analgesia versus continuous opioid infusion
Participants	Baseline Characteristics Inclusion criteria: Infants born no earlier than 34 weeks postmenstrual age and having a corrected age of no greater than 44 weeks at the time of enrollment, had a birth or current weight of at least 2 kg, underwent an abdominal or thoracic surgical procedure conducted by the pediatric general and thoracic surgery team, and expected to require opioids for at least 24 hours after the surgical procedure based on the opinion of the surgeon. Additionally, at least one parent was required to be able to read and speak English. Exclusion criteria: Authors excluded patients if they required vasopressors, had significant prior opioid exposure, or were expected to be chemically paralyzed after surgery. Pretreatment:
Interventions	Intervention Characteristics Continuous infusion versus bolus administration Dose regimen: Morphine parent/nurse‐controlled analgesia versus continuous opioid infusion (0.030 mg/kg/h) Description of procedure: A 250 mcg/mL solution of parent/nurse‐controlled morphine, 0.010 to 0.0125 mg/kg/h basal rate (0.060 mg/kg/h total maximum) was ordered; doses were rounded to the nearest microgram. Parents were instructed about signs of pain and told to: push the parent/nurse‐controlled analgesia button only when the child was awake and in pain; to never push the button when the child was asleep; and to notify their nurse if they felt their child’s pain was not well controlled. For the continuous opioid infusion group, morphine was ordered at 0.030 mg/kg/h, with a 0.030 mg/kg/h nurse bolus available each hour to a maximum of 0.060 mg/kg/h total. Parents were instructed on signs of pain and to notify their nurse if their child’s pain was not well controlled.
Outcomes	Pain assessed with validated methods during the administration of selected drugs Outcome type: Continuous outcome Average pain intensity over the time of the study. Participant pain intensity was assessed using the Revised‐Face, Legs, Activity, Cry, Consolability (Revised‐FLACC) scale.
Identification	Sponsorship source: The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Country: United States of America Setting: Neonatal Intensive Care Unit Comments: None Authors names: Michelle L. Czarnecki, Keri Hainsworth, Pippa M. Simpson, Marjorie J. Arca, Michael R. Uhing, Liyun Zhang, Ann Grippe, Jaya Varadarajan, Lynn M. Rusy, Mary Firary, StevenJ. Weisman Institution: Jane B. Pettit Pain and Headache Center, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin Email: mczarnecki@chw.org Address: Jane B. Pettit Pain and Headache Center, Children’s Hospital of Wisconsin, P.O. Box 1997, MS 792, Milwaukee, WI 53201
Notes	Mari Kinoshita on 29/08/2021 19:15 Included Method matches that of 3496 ‐ NCT 2013 (registry number not clearly stated in paper)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomization scheme was created by a statistician on the research team using Windows version 6.0 of “rand.exe” (http://block‐stratified‐ randomization.software.informer.com/). The clinical research coordinator used the scheme to assign participants to groups." Computer‐generated
Allocation concealment (selection bias)	Low risk	"The clinical research coordinator used the scheme to assign participants to groups."  Concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	"Based on our current practice, PNCA patients were managed by the APS, and COI patients were managed by the neonatology team. COI patients were checked on". Not blinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	"This study used an unblinded design." Not blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	"There were 371 screened patients, with the final sample consisting of 25 infants, 16 in the PNCA group and nine in the COI group (CONSORT diagram shown in Fig. 1). Four participants from each group were removed from the study early, but all eight had at least one post‐randomization outcome and were included in the modified intent‐to‐treat analyses." No major concern
Selective reporting (reporting bias)	Low risk	Protocol registered as NCT01823497
Other bias	Unclear risk	"The current trial was originally designed to randomize 30 patients into each study arm based on an a priori power analysis. As stated previously, constraints in funding, and difficulty recruiting, required early termination of the trial. Although most parents were open to the idea when initially approached, they declined enrollment owing to the randomized nature of the study. In fact, 39% (28 of 71 approached) declined enrollment, with many stating they wanted their surgeon to make decisions regarding their infant’s pain management. Another reason for the small sample size was the number of enrolled patients who, despite their infants originally seeming likely to require a PNCA/COI for post‐surgical pain, ultimately had an epidural placed during surgery. Of the 36 who were consented and randomized, 28% (n = 10) received an epidural." Early termination of the study