Effects of Different Doses of Fentanyl on the Sedation of Infants Under Mechanical Ventilation ; A Randomized Clinical Trial

1Department of Pediatrics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran 2Department of Clinical Pharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran 3Student Research Committee (SRC), Baqiyatallah University of Medical Sciences, Tehran, Iran 4International Otorhinolaryngology Research Association (IORA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

study evaluated the effects of 2 different dosages of fentanyl on the sedation of infants under mechanical ventilation.

Methods
This randomized clinical trial was conducted between July 2016 and March 2017 at Najmiyeh University Hospital, Tehran, Iran. Figure 1 shows a flowchart of the trial.Infants with a confirmed diagnosis of RDS based on chest radiography and physical examination by a single neonatologist were assessed for eligibility using simple random sampling method.Restless infants who were under mechanical ventilation were included in the trial.Infants with weights less than 2.5 kg or more than 4 kg as well as those with congenital heart disease, brain anomalies, or metabolic or chromosomal syndromes were excluded from the study.
After explaining the study process to parents and obtaining informed consent for participation, the infants were randomly allocated to 2 groups using the random number table.The first group (A) underwent treatment with fentanyl 0.5 μg/kg, and the second group (B) received 1 μg/kg of fentanyl.Demographic information and data on gestational age, birth weight, and method of delivery were recorded.Duration of mechanical ventilation, length of hospital stay, need for re-intubation, arterial oxygen pressure, and complications such as pneumothorax and hyporeflexia were recorded on a pre-designed checklist.
Normally distributed variables (approved by the 1-sample Kolmogorov-Smirnov test) were compared between groups using the independent sample t test.The chi-square test was used to compare categorical variables in the 2 groups.Mean and standard deviation (SD) were used to describe categorical variables.
For all study individuals, mean duration of hospitalization was 10.18 ± 3.74 days.Patients in group A and B were hospitalized for 10.36 ± 3.59 days and 10 ± 3.95 days, respectively (P = 0.642).Infants underwent mechanical ventilation for an average of 3.74 ± 1.78 days.Mean duration of mechanical ventilation was 3.96 ± 2.02 days in group A infants and 3.51 ± 1.5 days in group B infants (P = 0.459).Table 2 shows detailed data for those needing an additional dose during the trial.During the trial 27 (45%), 33 (55%), 16 (26.7%),and 9 (15%) infants required an additional dose on the first, second, third, and fourth day, respectively.Among all study infants, mean weight at the time of discharge was 2.82 ± 0.57 kg; mean weights at discharge of infants in groups A and B were 2.87 ± 0.56 kg and 2.76 ± 0.58 kg, respectively (P = 0.532).
Table 3 summarizes the data on respiratory rate, heart rate, need for mechanical ventilation, respiratory distress, mean arterial oxygen pressure, and mean arterial CO2 pressure in the 2 study groups.Mean respiratory rates were 70.58 ± 8.68 per minute before and 55.58 ± 11.53 per minute after intervention in all infants (P = 0.00).The mean respiratory rate was significantly decreased in each group after intervention; however, the means were not significantly different between the 2 groups after intervention (P = 0.068).Mean heart rates were 140 ± 10.81 per minute before and 138.26 ± 14.58 per minute after intervention in the study individuals (P = 0.171).

Discussion
The current study found no significant difference between the study groups for mean length of hospitalization; all study individuals were hospitalized for a mean of 10 days.Furthermore, there was no significant difference between the 2 groups for mean duration of mechanical ventilation.Although mean respiratory rate was significantly decreased in both groups after intervention, there was no significant difference between the 2 groups for mean respiratory rate.In contrast, mean heart rate was significantly lower in group B infants after intervention.Mean arterial oxygen pressure was significantly improved after intervention, but this improvement was not significantly different between the 2 groups.In addition, mean arterial CO2 pressure was not significantly decreased after intervention in either study group.
Some previous studies have assessed the sedative effects of fentanyl and its different doses on neonates who undergo mechanical ventilation.Ancora et al assessed the superiority of infusion and bolus administration of fentanyl in infants who undergo mechanical ventilation.Mechanically ventilated infants under 37 weeks gestational age were randomly allocated to groups for continuous infusion of fentanyl, placebos, and open-label boluses.The authors concluded that fentanyl infusion did not reduce prolonged pain; however, it was effective on acute pain. 14n another similar study, Roth et al evaluated the analgesic and sedative effects of fentanyl on infants undergoing mechanical ventilation for RDS.Infants in the intervention group received a fentanyl infusion at a mean

What Is Already Known?
Fentanyl is used in different dosages ranging from 0.5 μg/ kg to 4 μg/kg for sedating infants with the same outcomes.

What This Study Adds?
We found that prescription of both 0.5 μg/kg and 1 μg/ kg doses of fentanyl effectively reduces all parameters of respiratory distress such as heart rate and respiratory rate; however there is no significant difference between 2 groups.
Research Highlights dosage of 0.68 ± 0.24 μg/kg/h; these infants needed fewer sedatives and catecholamines in comparison to the control group.The authors concluded that fentanyl did not change heart rate or blood pressure.Their findings are not in line with those of the present study.Later meconium excretion and higher bilirubin levels were reported as side effects of fentanyl, the prescription of which has been suggested under indications. 15uinsburg et al evaluated the response of ventilated neonates to a single dose of fentanyl (3 μg/kg) before, 30 minutes after, and 60 minutes after administration.They reported that minimum and maximum heart rates were decreased and growth hormone levels were increased after analgesia in the fentanyl group.The authors further concluded that behavioral measures of pain associated with mechanical ventilation were reduced in the fentanyl group. 16

Conclusion
In conclusion, the findings of the present study suggest that doses of 0.5 μg/kg and 1 μg/kg fentanyl reduce all parameters of respiratory distress, including heart rate and respiratory rate; however, no significant difference between the 2 doses was observed.

Table 1 .
Pregnancy-Related Complications in Study Individuals

Table 2 .
Need for Additional Dose During Trial in Detail

Table 3 .
Respiratory Rate, Heart Rate, Need for Mechanical Ventilation, Oxygen Dependency, Mean Arterial Oxygen Pressure, and Mean Arterial CO2 Pressure in Study Groups