Table 2.
Demographic and pharmacokinetic parameters of morphine in neonates. The figures are means. The adult values 34 are normal and are used for comparison.
| Reference | Number of cases | Dose | Developmental stage | Age at treatment | Procedure | Half-life (hours) | Clearance (ml/min/kg) or (l/h/70 kg) | Distribution volume (l/kg) |
|---|---|---|---|---|---|---|---|---|
| 20 | 17 | 100-200 µg/kg + infusion | Preterm (26-34 weeks) | Day 1 | Analgesia | 8.75 | 2.4 ml/min/kg | 1.82 |
| 21 | 20 | 100 µg/kg | Preterm (10-28 weeks) Preterm (7-33 weeks) Term (3) |
<5 days | Analgesia | 10.0 7.4 6.7 |
3.4 ml/min/kg 9.6 ml/min/kg 15.5 ml/min/kg |
1.84 5.18 2.9 |
| 22 | 48 | 50 µg/kg + infusion | Preterm (24-27 weeks) Preterm (28-31 weeks) Preterm (32-35 weeks) Preterm (36-39 weeks) |
NA | Pain response control | 6.6 | 2.3 ml/min/kg 3.2 ml/min/kg 4.5 ml/min/kg 7.8 ml/min/kg |
2.2 2.4 2.6 3.2 |
| 23 | 898 | 100 µg/kg + infusion versus placebo | Preterm (22-38 weeks) | 5 days to 54 weeks | Ventilation + Analgesia | NA | Increased from 2.0 l/h/70 kg to 6.0 l/h/70 kg | 2.7 |
| 24 | 19 | 50 µg/kg diamorphine + infusion | Preterm (24-39 weeks) Term | 1-37 days | Ventilation | 11.1 (M3G) 18.2 (M6G) |
4.6 ml/min/kg | 0.55 (M3G) 1.03 (M6G) |
| 25 | 27 | 100 µg/kg | Term | 1 week to 6 months | Ventilation (n=4) or surgery (n=23) | 8.1 to 2.6 | 8.7-28.0 ml/min/kg | NA |
| 26 | 19 | 10-100 µg/kg + infusion | Preterm (12) Term (7) |
NA | Ventilation for respiratory distress | 9.6 | 2.6 ml/min/kg | 2.05 |
| 27 | 10 | 20-100 µg/kg/h | Preterm Term |
1-70 days | Ventilation | 6.8 (1-7 days) 3.9 (older) | 6.3 (1-7 days) 23.8 (older) | 2.9 |
| 28 | 14 | 100 µg/kg + infusion | Term | <7 days Lasting 14 days | Membrane oxygenation | NA | 2.2 l/h/70 kg, increased to 10.5 l/h/70 kg | 2.0, increasing to 5.0 |
| 29 | 11 | infusion | Term | NA | Membrane oxygenation | NA | 11.7 ml/min/kg | NA |
| 30 | 7 | NA | Term | 1 day to 12 months, lasting 40-103 hours | Membrane oxygenation | NA | 9.1 during increase 17.6 post-oxygenation |
NA |
| 31 | 184 | 100 µg/kg + infusion | Term | 0-3 years | Surgery | NA | 71 l/h/70 kg | 1.94 |
| 32 | 26 | 50 µg/kg + infusion diamorphine | Preterm (26-38 weeks) | NA | Surgery | 8.9±3.3 | 3.6 ml/min/kg | 2.7 |
| 33 | 13 | 100-200 µg/kg + infusion | Preterm (8) Term (5) |
NA | Surgery | 9.3 3.7 |
2.8 ml/min/kg 4.7 ml/min/kg |
2.4 1.7 |
| 34 | 20 | 50 µg/kg + infusion | Term | NA | Surgery | 6.6 | 2.1 ml/min/kg | 5.0 |
| 35 | Standard values | ---- | ---- | Adults | -------- | 1.9 | 35 ml/min/kg | 3.3 |
M-3G: Morphine-3-glucuronide; M-6G: Morphine-6-glucuronide; NA: Not available.