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Definition & Drugs

How do we define sedation and which drug are commonly used? In this article, we discuss the contium that is sedation and how what drugs we use.

Procedural Sedation

  • No generally accepted definition
    • The practice of procedural sedation is the administration of one or more pharmacological agents to facilitate a diagnostic or therapeutic procedure while targeting a state during which airway patency, spontaneous ventilation, airway reflexes and haemodynamic stability are preserved while alleviating anxiety and pain
    • Brief airway and ventilatory interventions may rarely be required
    • The intended potential to administer general anaesthesia, by definition, is not procedural sedation
    • Monitored Anaesthesia Care (MAC)
  • Increasing demand
    • Expanding the range of minimally invasive surgeries that can be performed under sedation
    • Increasing patient expectations
    • Increasing elderly population who have high general anaesthesia risk
  • In reality a continuum
    • Different target levels of sedation
      • Minimal
      • Moderate
      • Dissociative
      • Deep
  • Components of sedation
    • Anxiolysis
    • Analgesia
  • Know your procedures:
    • Duration: projected procedure time has a contingency plan for unexpected complications or delays
    • Prepare for stimulating components: periods of the procedure may require higher sedation than others
    • Analgesic requirements for the procedure
  • Know your patient:
    • Patients require anaesthesist lead sedation for a variety of reasons
    • Large interpatient variability
  • Know your surgeon:
    • Titrating sedation takes time as
    • Do not allow yourself to be placed under pressure to speed up the process
    • Different surgeons will have different expectations on the level of sedation, patient movement and ability to follow commands Know your setup:
    • Setup for the procedure
      • Access available to airway and IV
      • Location of emergency drugs and equipment
    • Monitoring and documentation of the patient’s vital signs during any procedure with sedation are crucial and obligatory
  • Recommendations for standards of monitoring during anaesthesia and recovery 2021
    • Procedural sedation requires minimum monitoring
    • ECG
    • SpO2
    • NIBP
    • EtCO2: Capnography should be used during procedural sedation whenever there is a loss of response to verbal contact
      – Setting expectation
    • Surgeon: Aim for a cooperative calm patient but the patient will be rousable and patient movement may occur
    • Patient: Not general anaesthesia expect to feel relaxed and not anxious but mild discomfort and some recall of the procedure may occur
  • Narrow therapeutic index
    • Devastating outcomes when used without adequate airway support, training and access to emergency drugs/ equipment
    • Sedation is statistically much more dangerous than anaesthesia
  • Respiratory depression
    • Synergy when sedatives are combined
  • Understanding of PK & PD of drugs used is required for the provision of safe sedation
    • Time to peak drug effect
    • Expected duration of effect
    • How the drug is metabolised
    • Potential reversal agents for the drug
    • Patient characteristics that will change how the drug is expected to behave
    • What the drug is likely to do
Caution: One should note there is a significant time delay (40seconds) for pulse oximeter readings

Midazolam

  • Sedative and hypnotic
  • Licensed for administration by non- anaesthetists
  • Titrated in small increments
    • Adults: 1 mg at a time
    • Children: 0.05-0.1mg/kg up to max of 1mg
  • Time to peak effect of each dose increment is approx 10 to 15 minutes can lead to overdose
  • Elderly patients and children are more susceptible to adverse effects
    • Paradoxical reaction occurs in <1% population
  • Reversed by flumazenil
    • Adults: 0.2mg by repeated increments to max of 1mg
    • Children: 0.01mg/kg (max 0.2 mg) repeated in increments to max of 0.05mg/kg or 1mg
    • Caution: Administration may result in seizures or arrhythmias

Remimazolam

  • Ultra short-acting benzodiazepine
  • The safety and efficacy of remimazolam in those <18 years have not been established
  • Combines the PD profile of midazolam but with the speed of onset and consecutive breakdown similar to that of remifentanil
  • Procedural sedation or general anaesthesia (licence varies on the country)
  • Powder for solution for injection
  • 20mg white powder reconstituted with 8ml of normal saline to 2.5mg/ml
  • Modulates the effect of GABA(A) receptors
  • Dosing recommendations
    • With opioid: 5mg bolus after the onset of opioid with increments of 2.5mg every 2 minutes
    • Without opioid: 7mg bolus with increments of 2.5mg every 2 minutes
    • If 5 doses of remimazolam within 15 minutes does not create desired effect alternative agents should be used
    • The maximum total dose in clinical trials was 33mg
  • For IV administration only
  • Time to peak effect is 3-3.5 minutes
  • Metabolised by plasma esterase
  • Short duration of action
    • Patients are fully alert 12-14 minutes from the last dose

Propofol

  • Potent sedative and general anaesthetic agent
  • Anxiolysis and antiemetic at a low dose
  • TCI models allow easy effect-site titration
  • Start low go slow
    • 0.5 μg.ml−1 and titrating upwards by 0.2 to 0.4 μg.ml−1 -Usually, a maximum of 2μg.ml−1 is recommended for sedation
    • Caution: wide interpatient variability

Remifentanil

  • Powerful analgesics and mild sedatives
    • Allows patients to tolerate painful procedures with minimal sedative effects
  • Strong respiratory depressant
  • Remifentanil has a similar PD profile to fentanyl and other opioids
  • Fast onset
  • Metabolised by plasma esterase therefore fast offset
  • Context insensitive half-time effects wear off in 3-4 minutes
  • Minto model
    • Most common TCI PK model for remifentanil
    • Start at target concentrations of 1 ng.ml−1 and titrate upwards in 0.5 ng.ml−1 increments
  • Nausea may be a feature at higher concentrations
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