Vaughn 1996.

Study characteristics
Methods	Study design: Double‐blind, randomized clinical trial Study grouping: Fentanyl continuous infusion versus bolus dosing every 2 hours
Participants	Baseline Characteristics Inclusion criteria: Infants between 36 and 52 weeks postmenstrual age at the time of studies, who were admitted to the neonate intensive care unit. Patients underwent a surgical procedure after which at least 24 hours of narcotic analgesia was likely to be needed. Exclusion criteria: Patients that required assisted ventilation before surgery were not eligible. Pretreatment: None
Interventions	Intervention Characteristics Continuous infusion versus bolus administration Dose regimen: Fentanyl by continuous infusion or bolus dosing every 2 hours Description of procedure: In the initial phase of the study, enrolled patients were randomly assigned to receive fentanyl by either continuous infusion beginning at 1 mcg/kg/h, or bolus dosing with a starting dose of 2 mcg/kg every 2 hours, thus providing equivalent cumulative dosing over time.
Outcomes	Pain assessed with validated methods during the administration of selected drugs Outcome type: Continuous outcome After initiating the study medications, an observational pain assessment was performed. The observational pain assessment tool used was an adaptation of the Infant Pain Scale (IPS). Duration of mechanical ventilation (days) Outcome type: Continuous outcome Time to extubation
Identification	Sponsorship source: Supported by the General Clinical Research Centers Program, National Center for Research Resources (NIH) Country: United States of America Setting: Neonate Intensive Care Unit Comments: None Authors names: Philip R. Vaughn, Susan F. Townsend, Elizabeth H. Thilo, Shirley McKenzie, Susan Moreland, Kerry Kawato Institution: Department of Pediatrics, University of Colorado School of Medicine and Department of Pharmacy, The Children's Hospital Email: Not provided Address: Pediatrics, University of Colorado Health Sciences Center, 4200 E Ninth Ave, BOX B‐195, Denver, CO, 80262
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Enrolled patients were randomly assigned to receive fentanyl by either continuous infusion (C) beginning at 1 pg/kg/h, or bolus dosing (B) with a starting dose of 2 kg every 2 hours, thus providing equivalent cumulative dosing over time." Not specified
Allocation concealment (selection bias)	Unclear risk	Not described in paper
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Caregivers were unaware of the patient’s group assignment (i.e. the caregivers did not know which of the two syringes contained the fentanyl)." Blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"Any intervention to support the patient was recorded by the bedside nurse. Apnea was determined by impedance pneumography and direct observation." Not stated whether these nurses were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	"A description of the patients enrolled in both phases of the study is shown in Table 2." No concern
Selective reporting (reporting bias)	Unclear risk	No registry reported so unable to compare to protocol
Other bias	Unclear risk	"A significant limitation of the study is demonstrated by the larger proportion of patients who remained intubated and ventilated in phase 2 (6 of 13) compared with phase 1 (1 of 7). The study design did not incorporate a systematic approach to weaning ventilator support, and therefore interpretation of this observation is difficult." See quote

APS: Acute Pain Service
CM: continuous morphine
COI: continuous opioid infusion
CS: COMFORT scale
FLACC: Face, Legs, Activity, Cry, Consolability scale
IM: intramuscular
IPS: Infant Pain Scale
i.v.: intravenous
PNCA: parent‐ or nurse‐controlled analgesia
VAS: visual analogue scale