Dose and Administration

1. Dose is 100 micrograms/kg/hr for 2 hours followed by 25 micrograms/kg/hr thereafter.
2. Lower infusions of 10 -20 micrograms/kg/hr may be used but have not been shown to achieve adequate analgesic levels in preterm infants.

1. 50 - 200 micrograms/kg/dose by slow IV injection, IM or SC. Repeat as required (usually 4-hourly).
2. Usual starting dose 100 micrograms/kg. Titrate dose against clinical response. Intermittent dosing may lead to intermittent effect.
3. A bolus of a continuous infusion may be given for short-term additional sedation.  This should be charted on the stat drug chart as:

• Bolus morphine infusion with the strength specified and the volume and dose specified.
  e.g.  For a 1kg baby, "Bolus morphine infusion (25 micrograms/kg in 0.5ml) - dose 2ml (100micrograms) IV"

Indications

1. Analgesia
2. Sedation

Contraindications and Precautions

1. Known hypersensitivity to opiates
2. Hypovolaemia, hypotension
3. Caution in preterm infants, especially very immature
4. Caution in neonates with hepatic and renal impairment
5. Caution in neonates with cardiac arrhythmias

Clinical Pharmacology

Morphine sulphate is a narcotic analgesic which stimulates opioid receptors in the central nervous system (mimics actions of encephalins and β endorphins). Produces respiratory depression by direct effect upon brain stem respiratory centres. No major effect upon cardiovascular system in analgesic doses. Resistance and capacitance vessels are dilated by the opioids. Gastrointestinal secretions and motility are decreased while tone is increased. Stimulates smooth muscle of biliary and urinary tracts.

Well absorbed from gastrointestinal tract but high first pass hepatic metabolism: parenteral route of administration is preferred. Low binding (20%) to human plasma protein. Hepatic metabolism to glucuronide and other metabolites. Excretion via the kidney - significant amounts of unchanged drug in the neonate. The pharmacokinetics of morphine in the neonate are very variable.

Rapid onset of action after parenteral administration. Peak effect 20-60 minutes. Duration of analgesic effect variable (may persist up to 7 hours). Analgesic effects occur with plasma concentrations 100-150 ng/ml. Respiratory depression may occur with plasma concentrations >300 ng/ml. Accumulation can occur but is rarely a clinical problem.

Possible Adverse Effects

1. Respiratory depression
2. Gastrointestinal disturbances (ileus and delayed gastric emptying, cramps, constipation).
3. Hypotension
4. Urinary retention
5. Physical dependence

Special Considerations

1. Morphine is the drug of choice for most situations requiring pain relief.
2. Administer parenterally appropriate length of time compatible with the infant's needs for analgesia and/or sedation.
3. Wean slowly after prolonged use of morphine, greater than 2 weeks.
4. Management of morphine toxicity: stop morphine, support infant, (ventilation, external cardiac massage, volume expansion etc.), naloxone (0.1 - 0.2 mg/kg/dose IV, or IM).
5. Naloxone is never used for babies at risk of neonatal abstinence syndrome.