20A17: Exam Report

Discuss the advantages and disadvantages of the use of an intravenous infusion of fentanyl in comparison to morphine.

27% of candidates passed this question.

These are both level 1 drugs commonly used as an infusion in daily practice. This question specifically asked the candidates to frame their answers around an intravenous infusion of fentanyl in comparison to morphine. A tabular listing of general properties of the two drugs highlighting the differences between the drugs would not score well. The question asks for a
considered response that should focus on context sensitive half-life, compartments and metabolism, instead many focused on the speed of onset and potency, which are minor considerations when drugs are given for long periods by infusion. Candidates often demonstrated a superficial knowledge of key pharmacokinetic concepts with limited application of these
principles in the context of an intravenous infusion. Better answers also related the above to various relevant pharmacodynamic influences such as age, liver and renal impairment.

K4ii / 20A17: Discuss the advantages and disadvantages of an IV infusion of fentanyl in comparison to morphine

Use

  • Currently the two commonest used analgesic agents in ANZ ICUs for analgesia and sedation

Cost

  • Similar; Morphine 10mg A$0.52 cf Fentanyl 100mcg $0.35

Pharmacokinetics

PPB

M

35%

F

84%

Vd

M

192L

F

312L

Time to Analgesia

M

10-40min

F

6-15min

Metabolism

M

Hepatic via Glucuronidation

M3G (>80%)

M6G (<10%)

F

N-Demethylation to Norfentanyl

Active Metabolites

M

M6G

F

minimal

Excretion

M

Renal, Biliary

<5% unchanged

F

Renal

10% unchanged

CSHT

M

N/A

F

200mins

  • F has a high level of PPB which in the malnourished ICU patient will see more free active fentanyl
  • F has a much larger Vd which explains its prolonged CSHT and ‘stores’ in the body
  • Morphine metabolism produces active metabolites which will accumulate in renal failure
  • Both require hepatic metabolism, through different enzyme systems, F is metabolized through the P450 pathway and drugs which interfere with this system will increase/decrease its effects
  • Elimination of M will be prolonged with renal failure
  • Although F is hepatically metabolized, it can be given to patients with impaired liver function (studies confer no change in clearance when pts with cirrhosis were compared to those with normal liver fn)

Adverse Effects

M

Nausea, vomiting, delayed gastric emptying, constipation, bowel distention, paralytic ileus, Sphinter of Oddi spasm, urinary retention, miosis, dizziness, sedation, drowsiness, eurphoria

Histamine release – non immune mediated, however amount of histamine release has large inter individual variability.  Can precipitate bronchospasm

Avoided in the pregnant ICU patient as it crosses the placenta, the neonate liver has reduced conjugation capacity and an immature BBB results in increased sensitivity to M

F

Chest wall rigidity, respiratory depression

Overuse of both opioids can have additional unwanted effects in the ICU patient; prolonged sedation, intubation, mechanical ventilation, LOS, delirium, weakness, PI and delayed long term recovery