Which Agent is Most Appropriate?

• Midazolam is a fast acting water soluble benzodiazepine that has been used for procedural sedation in the ED for approximately 30 years. It has no analgesic properties.
  • Midazolam should be prepared as a 1 mg in 1 ml solution [7].
  • The recommended intravenous dose for midazolam is 2-2.5 mg initially, with further 1mg doses repeated after 2-5 minutes, titrated to effect [1].
  • The initial dose is 0.5-1 mg in adults older than 60 and the chronically ill or debilitated, with 0.5mg aliquots thereafter.
  • Midazolam should be given at a rate of approximately 1 mg over at least 30 seconds; the time to effect is approximately 3 minutes.
  • A total dose of more than 5 mg is not usually necessary in a healthy young adult; less than 3.5 mg in adults older than 60 and the chronically ill or debilitated.
• An important safety feature of midazolam is the availability of flumazenil. This rapidly reverses the depressant effects of benzodiazepines. It should not be used routinely, but only in cases of emergency.
  • Care must be taken as flumazenil may have a shorter duration of action than the sedative agent, resulting in re-sedation [7].
  • The use of flumazenil should be regularly audited as a marker of excessive dosage of midazolam [3].

Propofol

• Propofol is a lipophilic agent that is thought to enhance GABA inhibitory neurotransmission. It is used widely in anaesthesia induction and maintenance [1].
• Propofol is used for procedural sedation in many EDs worldwide [10]. It has a rapid onset and recovery from sedation with complication rates that are comparable with midazolam, making it particularly useful for procedures that require a very brief period of sedation. It is reported to be associated with less apnoea than midazolam, but with slightly more aspirations and intubations [9]; however, formal comparison with other agents used in PSA was inconclusive [11].
• Propofol is associated with profound hypotension and respiratory depression, and frequent induction of deep sedation or general anaesthesia [1].
  • Most patients will require 0.5 -1 mg/kg for onset of sedation; further doses of 0.25-0.5mg/kg can be given every 3-5 minutes, titrating to effect.
  • 10-20mg boluses given slowly should be used in the elderly and chronically ill or debilitated [1].
• The respiratory depressant effects of midazolam and propofol are enhanced when used in combination with an opiate. When opiate analgesia is required, it should be given first and allowed time to become maximally effective before sedative administration.
• Appropriate training is required prior to its use, following local protocols.

Ketamine

• Ketamine is a dissociative anaesthetic and analgesic that produces a trance-like state due to dissociation between the limbic and cortical systems.
• Patients sedated with ketamine appear to be awake and have little cortical depression, but the awareness of external stimulation is blocked. It is unique in that it produces a state in which respiration and airway reflexes are usually maintained.
• A dose of 1 mg/kg intravenously delivered over at least one minute, or 4-5 mg/kg intramuscularly will rapidly produce a dissociative state lasting up to 30 minutes.
  • A reduced dose in the elderly of 10-30mg intravenously is appropriate.
• A problem is emergence phenomena. This may be related to pre-sedation agitation and can be attenuated by minimising stimulation during recovery and avoiding premature awakening.
  • Administration of a benzodiazepine, to treat or prevent emergence phenomena is likely to prolong the recovery phase.
• Ketamine is also associated with sympathetic stimulation causing tachycardia and hypertension.
• Ketamine is relatively contraindicated in patients with airway instability or tracheal pathology, a high predisposition to laryngospasm or apnoea, severe cardiovascular disease, CSF obstructive states, previous psychotic illness, hyperthyroidism or thyroid medication use, globe injury or glaucoma and porphyria [1].

Nitrous oxide

• Nitrous oxide has been used as an inhalational analgesic and anaesthetic agent since the 1800s.
• Its analgesic and anxiolytic effect is reliable and dose related and the recovery is rapid once inhalation of the agent ceases.
• It is usually administered from cylinders containing the gas premixed with oxygen at a concentration of 50%, delivered via a demand valve which allows some patient control.
• It is useful as a sole analgesic for minor procedures or as an adjunct to opiate analgesia for moderate to severe pain [12].
• When the inspired concentration of nitrous oxide reaches 70% (the routine anaesthetic dose) consciousness is lost and the same standard of care as general anaesthesia is required [13].
  • It is important to be aware of this if a method of delivery other than that described above is used, i.e. an anaesthetic machine. The concentration of oxygen in the inspired gas must never be less than 30%.

Nitrous oxide rapidly diffuses into closed air spaces causing volume expansion and pressure effects. It is contraindicated when there is any suspicion of pneumothorax, bowel obstruction, ruptured viscera or decompression illness (potential air embolism).”