Pharmacological agents

The pharmacological agents typically used for procedural sedation in UK emergency medicine practice are listed, along with their properties, in Table 4.

DRUG DOSE ONSET (MIN) PEAK EFFECT (MIN) DURATION
Morphine 0.1mg/kg iv titrated to effect 1-2 10-15 2-4hrs
Fentanyl 1-2mcg/kg 1-2 2-5 20-30min
Nitrous oxide 10-70% 1-2 2 Rapidly wears off
Ketamine 1mg/kg iv titrated to effect given over 60s

2 – 4mg/kg im

1-2

2-5

2

5

30 min

90 min

Midazolam 0.02-0.1mg/kg iv adult titrated to effect

0.025-0.05mg/kg iv child titrated to effect

1-2 3-4 30 min
Propofol 1.0mg/kg bolus 1 1-2 5-10 min

In general you should deliver these agents via the intravenous route. The onset is quick and reliable, allowing you to titrate the drug appropriately. The intramuscular route should be reserved for children (Section 7) and those adults with learning difficulties or behavioural problems. It is worth emphasizing the need to use smaller initial doses in the elderly6 and allowing the drug extra time to take effect, given the slower arm-brain circulation time in such patients. In contrast, those patients with regular alcohol consumption that comfortably exceed current recommendations may require larger sedative doses than usual to achieve the required level of sedation. Titration is not necessarily straightforward, the therapeutic window being narrow in these cases. All the drugs listed have the capacity to produce deeper levels of sedation and even anaesthesia if used in excess. Further, combinations of drugs, especially sedatives and opioids, should be employed with caution. The opioids should be given first to allow time to become maximally effective before any sedative is added.

You should be familiar with two reversal agents, naloxone and flumazenil. Naloxone should be titrated 100-200mcg every 1-2mins to reverse respiratory depression following opioid administration. Its effects may wear off before the opioid is cleared so you should consider extended patient monitoring. Naloxone may precipitate withdrawal in opioid dependent patients. In excess it will also antagonise analgesia.

Give flumazenil in small increments of 100-200mcg every one minute to reverse respiratory depression following benzodiazepine use. Use it with caution in those on long term benzodiazepines to avoid withdrawal symptoms.

The role of propofol for deep sedation in adult patients is covered in detail in a separate RCEM learning module. A single analysis of 1008 patients sedated with propofol, demonstrated a sentinel adverse event rate of 1% with no adverse outcomes6.

The dissociative drug ketamine offers a unique sedative state that will be considered in detail in the section on sedation for children.

Adverse Events Associated with Specific Procedural Sedation and Analgesia Medications

Medication Associated Adverse Events
Propofol Respiratory depression, hypotension, decreased cardiac output
Etomidate Nausea, vomiting, myoclonus, adrenal suppression
Ketamine Tachycardia, hypertension, increased cardiac output, hypersalivation, emergence phenomenon, laryngospasm
Midazolam Hypoventilation , hypoxemia, hypotension, paradoxical stimulatory effect
Fentanyl Pruritus, nausea, vomiting, respiratory depression

Learning Bites:

  • If using benzodiazepine/opioid combinations give the opioid first to allow time for it to become maximally effective before any sedative is added
  • Use smaller initial doses of sedative in the elderly, debilitated and acutely ill patients
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