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Questions Answered: 127

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126
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Procedural Skills (SLO6)

Question 25 of 127

You are discussing procedural sedation in an Emergency Department peer to peer teaching session. Which of the following best describes the mechanism of action of propofol?

Answer:

Propofol is a lipophilic agent that is thought to enhance GABA neurotransmission.

Procedural Sedation: Drugs

Effective sedation

Effective procedural sedation requires:

  • Analgesia
    • Pain experienced by the patient should be treated with analgesia rather than sedation
    • Pain should be assessed and managed prior to starting sedation using the WHO pain ladder principles and the need for ongoing pain relief post-procedure considered
    • Where opiate pain relief has been given prior to procedural sedation, doses of sedatives should be adjusted accordingly
  • Anxiolysis
    • Non-pharmacological methods of reducing anxiety are often the most effective and include consideration of the environment and patient comfort
    • Environment is particularly important for children and patients with dementia or learning difficulties
    • Family members often provide invaluable support and distraction
    • Most painful procedures are best performed with the patient supine
  • Sedation
    • For most procedures in the ED, the level of required sedation will be moderate to deep, this should be determined in advance
  • Amnesia
    • A degree of amnesia will minimise unpleasant memories associated with the procedure

In most circumstances a combination of short acting analgesics and sedatives are required as the only pharmacological agent that has the potential to provide analgesia, sedation, anxiolysis and amnesia is ketamine.

Choice of sedation agents

The appropriate choice of pharmacological agents for procedural sedation depends on:

  • The nature of the procedure
  • The planned level of sedation
  • Training and familiarity of the sedating practitioner with potential pharmacological agents
  • Patient factors
  • The local environment

Having selected the appropriate drugs for the needs of the patient, doses of the pharmacological agents need to be tailored to the individual patient to deliver the required effects. Great care should be used when administering sedatives because of:

  • Slow and variable onset time
  • Inter-patient variability in dose requirement
  • Synergistic action between drugs

Common pharmacological agents for procedural sedation in adults

  • Midazolam
    • 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.
    • 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.
  • Propofol
    • Propofol is a lipophilic agent that is thought to enhance GABA inhibitory neurotransmission.
    • Propofol is used for procedural sedation in many EDs worldwide. 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.
    • Propofol is associated with profound hypotension and respiratory depression, and frequent induction of deep sedation or general anaesthesia.
    • 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.
  • 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 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.
Drug Propofol Midazolam Ketamine
Mode of action Positive modulation of GABA inhibitory neurotransmission Short-acting benzodiazepine NMDA-receptor antagonist
Effects Sedation and amnesia Sedation and amnesia Dissociative sedation, amnesia, analgesia
Side effects Hypotension, respiratory depression, pain at site of injection Respiratory depression, hypotension, paradoxical disinhibition and agitation at low doses in children, accumulates in adipose tissue which can prolong sedation (elderly, obese and patients with hepatic or renal disease at risk) Tachycardia, hypertension, laryngospasm, hallucinations, nausea and vomiting, hypersalivation, increased intracranial and intraocular pressure
Route IV IV IV
Initial onset time 30 sec - 1 min 1 - 2 min 30 sec - 1 min
Peak effect time 1 - 2 min 3 - 4 min 1 - 2 min
Initial dose
  • Adult: 0.5 - 1 mg/kg
  • Elderly: 10 - 20 mg
  • Adult: 1 - 2 mg
  • Elderly: 0.5 mg
  • Adult: 1 mg/kg
  • Elderly: 10 - 30 mg
  • IM: 4 - 5 mg/kg
Repeat dose
  • Adult: 0.5 mg/kg every 3 - 5 mins
  • Elderly: 10 - 20 mg
  • Adult: 1 - 2 mg after 2 - 5 mins
  • Elderly: 0.5 mg
  • Adult/Elderly: 0.25 - 0.5 mg/kg every 5 - 10 min
  • IM: 2 - 2.5 mg/kg every 5 - 10 min

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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