Madathil 2021b.

Study characteristics
Methods	Open‐label randomized trial. In the first part of this study, lower doses were used; see Madathil 2021a.
Participants	27 neonates Inclusion criteria: hemodynamically stable infants with type 1 ROP requiring laser photocoagulation. Exclusion criteria: anemia, grade III to IV intraventricular hemorrhage, congenital malformations, patent ductus arteriosus or necrotizing enterocolitis and the anticipated duration of procedure was more than 30 min; infants receiving respiratory support and/or admitted to NICU. Fentanyl group (n = 13; mean GA 30.3 SD 1.3 weeks; mean BW 1281.6 SD 267 g) Ketamine group (n = 14; mean GA 30.5 SD 2.4 weeks; mean BW 1301.0 SD 338 g)
Interventions	Fentanyl group: 2 μg/kg bolus, followed by a continuous infusion of 2 μg/kg/h increased to a maximum of 5 µg/kg/h (intravenously) Ketamine group: 1 mg/kg bolus, followed by further intermittent bolus doses of 0.5 mg/kg given to a maximum of 4 mg/kg (intravenously)
Outcomes	PIPP‐R scores measured every 15 min less than 7, proportion of the procedure time the infant spent crying less than 5% apnea during and postprocedure, need for supplemental oxygen during and postprocedure, change in mean cardiorespiratory stability scores requiring up‐gradation of respiratory support, hemodynamic instability requiring fluid boluses or vasoactive support, feed intolerance, urinary retention, need for NICU admission for 24 hours or longer
Funding sources	The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not‐for‐profit sectors.
Declaration of interest among the primary researchers	None declared.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Low risk	Quote: "We used serially numbered, sealed and opaque envelopes for allocation concealment. The unit nurse opened the envelope and assigned the infant to a group"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Unblinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "the outcome assessors were blinded to the groups"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcomes are reported for all randomized infants—see Fig 1.
Selective reporting (reporting bias)	Low risk	Quote: "Trial registration number CTRI/2018/03/012878"
Other bias	Unclear risk	Quote: "Small number of infants enrolled in the second phase of the study due to logistical constraints as we had to stop the trial after achieving the target sample size." "Accordingly, the study steering committee recommended revision of the regimens: higher dose of intravenous fentanyl (intravenous bolus dose of 2 µg/ kg followed by an intravenous infusion of 2 µg/kg/ hour to maximum of 5 µg/kg/hour) and intravenous ketamine (bolus dose of 1 mg/kg followed by intermit‐ tent bolus doses of 0.5 mg/kg to a maximum of 4 mg/kg) were recommended. Subsequently, we enrolled 27 more infants (13 in fentanyl group and 14 in ketamine group). The results are described separately as initial phase and revised regimen phase"