| Study characteristics |
| Methods |
Single‐centre double‐blind randomised controlled trial |
| Participants |
24 mechanically ventilated infants were recruited
Inclusion criteria: gestational age ≥ 36 weeks with postnatal age no greater than 60 days; intubation within the last 12 hours; expected analgesia and sedation requirement due to mechanical ventilation for a further 12 to 96 hours
Exclusion criteria: CNS insult (e.g. asphyxia); structural brain disorder affecting ability to assess the level of sedation |
| Interventions |
Fentanyl group (n = 12): 3 mcg/kg/hour combined with midazolam 50 μg/kg/hour. Subsequently, opioid was adjusted in steps of 1 μg/kg/hour (maximum 10 mcg/kg/hour) to achieve and maintain a Hartwig score between 9 and 13
Remifentanil group (n = 12): 9 μg/kg/hour combined with midazolam 50 μg/kg/hour. Subsequently, opioid was adjusted in steps of 3 μg/kg/hour (maximum 30 mcg/kg/hour) to achieve and maintain a Hartwig score between 9 and 13
Pre‐medication for endotracheal intubation was given and boluses as needed to keep the infant sedated and pain‐free until the start of study medication, which had to be started at the latest 12 hours after intubation. Increased dosage of midazolam and boli of thiopental were allowed. If analgesia and sedation were insufficient despite the maximum allowed opioid and midazolam dosage, the infant was excluded from the study |
| Outcomes |
Primary outcome: extubation time (time from cessation of opioid infusion until extubation)
Secondary outcomes: efficacy in analgesia and sedation (Hartwig score); haemodynamic stability (MBP, HR); adverse effects; opioid tolerance (number of doses, number of dose adjustments); opioid withdrawal (Finnegan score); opioid‐induced hyperalgesia (CHIPPS Scale score and Flexion Withdrawal Reflex threshold) in the first 48 hours after extubation |
| Notes |
Of 24 infants randomised, 1 was withdrawn from the fentanyl group because of insufficient analgesia despite the maximum allowed dosage, and 2 were withdrawn from the remifentanil group because of protocol deviation |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Computer‐generated randomisation list |
| Allocation concealment (selection bias) |
Low risk |
Allocation concealment was ensured by the central pharmacy of the hospital |
| Blinding of participants and personnel (performance bias) |
Low risk |
Interventions were masked; the trial was stated to be double‐blinded |
| Blinding of outcome assessment (detection bias) |
Low risk |
Interventions were masked; the trial was stated to be double‐blinded |
| Incomplete outcome data (attrition bias) |
Unclear risk |
If analgesia and sedation were insufficient despite the maximum allowed opioid and midazolam dosage, the infant was excluded from the study (not considered for the ITT analysis) |
| Selective reporting (reporting bias) |
High risk |
Outcomes reported in the article seemed much more than those established in the protocol. Moreover, not all outcomes in the protocol were reported in the article (discharge time from the PICU) |
| Other bias |
Low risk |
Study appears to be free of other sources of bias |
