Conversion from prolonged intravenous fentanyl infusion to enteral methadone in critically ill children

Table 1 Baseline characteristics of rapid and slow conversion groups

	Rapid conversion groupa (n = 21)	Slow conversion groupb (n = 21)	P value
Age, yr (median, IQR)	1 (0.3-3.5)	2 (0.8-4)	0.95
Gender, male (%)	14 (67%)	9 (43%)	0.21
Weight, kg (median, IQR)	10 (5.5-14.3)	9.6 (6.8-15.9)	0.88
PRISM III (mean ± SD)	11.4 ± 9	16.1 ± 9.9	0.13
Admitting diagnosis, n (%)			1
ARDS/acute lung injury	14 (67)	14 (67)
Other (sepsis, seizures)	7 (33)	7 (33)
Pre-existing tracheostomy, n (%)	6 (29)	6 (29)	1
Duration of IV fentanyl infusion prior to initiation of enteral methadone, d (median, IQR)	9 (8-14)	10 (8-21)	0.48
Maximum dose of IV fentanyl infusion, μg/kg per hour (median, IQR)	6 (4-7)	6.75 (4-9.25)	0.41
Cumulative dose of IV fentanyl infusion at time of initiation of enteral methadone, mg/kg (median, IQR)	1.48 (1.11-1.92)	1.64 (1.03-1.98)	0.49
Concomitant sedative and analgesic infusions			0.61
Benzodiazepine, n (%)	18 (86)	20 (95)
Ketamine, n (%)	0 (0)	0 (0)
Dexmedetomidine, n (%)	0 (0)	0 (0)

^aRapid conversion group: Patients who were completely converted from IV fentanyl infusion directly to enteral methadone in 48 h or less;

^bSlow conversion group: Patients who were completely converted from IV fentanyl infusion directly to enteral methadone in more than 48 h. IQR: Inter-quartile range; SD: Standard deviation; PRISMIII: Pediatric risk of mortality; ARDS: Acute respiratory distress syndrome; IV: Intravenous.

Table 2 Conversion from intravenous fentanyl infusion to enteral methadone in rapid and slow conversion groups

	Rapid conversion groupa (n = 21)	Slow conversion groupb (n = 21)	P value
Dose of IV fentanyl infusion at initiation of enteral methadone, μg/kg per hour (median, IQR)	4 (3-4)	4.5 (3.6-7)	0.23
Adjustments in scheduled enteral methadone dose			< 0.05
Increase in dose	15	33
Decrease in dose	17	3
Opioid rescues in first 96 h of transition per patient (median, IQR)	3 (1-7)	12 (4-17)	< 0.05
0-24 h	0 (0-2)	3 (0-4)	< 0.05
24-48 h	1 (0-2)	2 (1-6)	0.02
48-72 h	0 (0-1)	1 (1-6)	0.01
72-96 h	0 (0-2)	2 (0-4)	0.12
Opioid rescues in first 96 h of transition by agent			< 0.05
Morphine	44	51
Fentanyl	51	210
Concomitant medications administered in first 96 h of transition (number of administrations)			0.6
Benzodiazepines	32	40
Clonidine	5	3
Barbiturates	2	8
NSAIDS	2	2
Neuromuscular blockers	4	6
Acetaminophen	9	10

^aRapid conversion group: Patients who were completely converted from IV fentanyl infusion directly to enteral methadone in 48 h or less;

^bSlow conversion group: Patients who were completely converted from IV fentanyl infusion directly to enteral methadone in more than 48 h. IV: Intravenous; IQR: Inter-quartile range; NSAIDS: Non-steroidal anti-inflammatory drugs.

Table 3 Clinical outcomes in rapid and slow conversion groups

	Rapid conversion groupa (n = 21)	Slow conversion groupb (n = 21)	P value
Ventilator free days at 28 d, d (median, IQR)	18 (13.3-18.8)	8 (1.5-10.8)	< 0.05
Total PICU length of stay, d (median, IQR)	17 (12-24)	38.5 (24.8-68.5)	0.05

^aRapid conversion group: Patients who were completely converted from IV fentanyl infusion directly to enteral methadone in 48 h or less;

^bSlow conversion group: Patients who were completely converted from IV fentanyl infusion directly to enteral methadone in more than 48 h. IQR: Inter-quartile range; PICU: Pediatric intensive care unit.

Table 4 Example of dose conversion from intravenous fentanyl infusion directly to enteral methadone

A 10-kg child is receiving IV fentanyl infusion of 5 mcg/kg per hour. The total daily fentanyl dose is 5 μg/kg per hour × 24 h = 1.2 mg/d

Dose conversion ratio - methadone:fentanyl = 2.5 (rounded up from 2.3 observed in rapid conversion group in the present study that converted from IV fentanyl infusion directly to enteral methadone within 48 h) based on potency, half-life and enteral bioavailability

Total daily dose of enteral methadone = 2.5 × 1.2 mg/d = 3 mg/d administered in 2 divided doses, i.e., 1.5 mg dosed every 12 h

Following the second dose of enteral methadone, the IV fentanyl infusion is decreased by 50% to 2.5 mcg/kg per hour

Following the third dose of enteral methadone, the IV fentanyl infusion is decreased again by 50% to 1.25 mcg/kg per hour

Following the fourth dose of enteral methadone, the IV fentanyl infusion is discontinued

IV: Intravenous.