Neonatal Intensive Care Drug Manual

Schedule 8 (S8) medicine. Must be stored and handled according to local S8 drug policy.

Sedation.

0.5–4 microgram/kg/dose over 3−5 minutes every 2−4 hours

0.5–5 microgram/kg/hour. General starting dose: 1 microgram/kg/hour. Titrate using a validated pain score.

2−4 microgram/kg bolus. Wait at least 3 minutes for onset of action after giving the dose.

DOUBLE STRENGTH continuous IV infusion

Neonates < 1 kg

Using 100 microgram/2 mL injection draw up 1 mL (50 microgram fentanyl)) and add 24 mL sodium chloride 0.9% to make a final volume of 25 mL with a concentration of 2 microgram/mL.
Neonates ≥ 1 kg

Using 100 microgram/2 mL injection draw up 1 mL (50 microgram fentanyl)) and add 9 mL sodium chloride 0.9% to make a final volume of 10 mL with a concentration of 5 microgram/mL.

As above for IV bolus.

IV infusion via syringe pump

Full cardiorespiratory monitoring is required.

Monitor for urinary retention.

Withdrawal has been reported in patients who have received continuous infusions for >5days.

Chest wall rigidity can occur at higher doses.

May cause respiratory depression.

May cause urinary retention.

May decrease intestinal motility.

When given in combination with amiodarone can cause profound bradycardia, sinus arrest and hypotension.

Muscle/chest wall rigidity (usually naloxone responsive). Naloxone 0.01−0.04 mg/kg reversed muscle rigidity immediately allowing resuscitation in a case series of 8 patients.

At high doses can cause neuro-excitation and rarely seizure like activity/myoclonic movements.

Respiratory depression.

Bradycardia (usually atropine responsive).

Urinary retention.

Y-site: Abciximab, adrenaline hydrochloride, amiodarone, anidulafungin, atracurium, atropine, bivalirudin, caffeine citrate, caspofungin, cisatracurium, dexamethasone, doripenem, esmolol, haloperidol lactate, heparin sodium, hydrocortisone sodium succinate, hyoscine hydrobromide⁸, ketorolac, labetalol, levomepromazine, linezolid,, metoclopramide, midazolam, milrinone, palonosetron, pancuronium, potassium chloride, remifentanil, vecuronium

It blocks endocrine stress responses.

It causes less histamine release than morphine.

It decreases pain-induced increases in pulmonary vascular resistance.

Opioids are to be used selectively based on clinical judgment and evaluation of pain indicators, although there are limitations to pain measurement in newborns¹ (LOE 1 GOR B).

A short course of low dose fentanyl by infusion reduces behavioural sedation scores, O₂ desaturations and neuroendocrine stress responses in preterm ventilated infants² (LOE II, GOR B).

Continuous infusion of fentanyl in the post-operative period achieves acceptable pain control but there may be increased need for ventilator support (LOE II, GOR C). (LOE II, GOR C).

In very preterm infants on mechanical ventilation, continuous fentanyl infusion plus boluses of fentanyl reduces acute pain and increases side effects but does not reduce prolonged pain compared with boluses of fentanyl alone (LOE II GOR B). (LOE II GOR B).

Safety

When controlling for other variables, the cumulative fentanyl dose did not correlate with neurodevelopmental outcomes in very low birth weight infants (LOE III GOR C). (LOE III GOR C).

Tolerance may develop to analgesic doses⁷.

Significant withdrawal symptoms have been reported in patients treated with continuous infusion for 5 days and longer (LOE IV GOR D).

Pharmacokinetics

Fentanyl is metabolised in the liver (CYP3A4) and excreted in the urine. There is wide variability in apparent volume of distribution and serum half-life can be up to 15 hours. There is significant correlation between postnatal age and total body clearance⁸.

2. Lago P, Benini F, Agosto C, Zacchello F. Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease. Arch Dis Child Fetal Neonatal Ed. Nov 1998;79(3):F194–197.

3. Vaughn PR, Townsend SF, Thilo EH, McKenzie S, Moreland S, Denver KK. Comparison of continuous infusion of fentanyl to bolus dosing in neonates after surgery. Journal of pediatric surgery. Dec 1996;31(12):1616–1623.

4. Ancora G, Lago P, Garetti E, et al. Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation. The Journal of pediatrics. Sep 2013;163(3):645–651 e641.

5. Fahnenstich H, Steffan J, Kau N, Bartmann P. Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants. Critical care medicine. Mar 2000;28(3):836–839.

6. Lammers EM, Johnson PN, Ernst KD, et al. Association of fentanyl with neurodevelopmental outcomes in very-low-birth-weight infants. The Annals of pharmacotherapy. Mar 2014;48(3):335–342.

7. Arnold JH, Truog RD, Scavone JM, Fenton T. Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion. The Journal of pediatrics. Oct 1991;119(4):639–643.

8. Santeiro ML, Christie J, Stromquist C, Torres BA, Markowsky SJ. Pharmacokinetics of continuous infusion fentanyl in newborns. J Perinatol. Mar-Apr 1997;17(2):135–139.

9. Fahnenstich H, Steffan J, Kau N, Bartmann P. Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants. Critical care medicine. Mar 2000;28(3):836-839.

10. Australian Injectable Drugs Handbook, 6th Edition, Society of Hospital Pharmacists of Australia 2014.