Sedation

Sedation is a mainstay of intensive care therapy and is indicated for:

Relative indications also include:

  • ↓ Patient anxiety and distress
  • Rest
  • ↓ Distress
  • ↓ Awareness of confronting environment

However, these are preferably managed by non-pharmacological means. Options include:

  • Access to visitors
  • Good communication
  • Positive reinforcement
  • Comforts
    • Ice chips
    • Comfortable mattress
    • Music and entertainment
    • Circadian routine

Assessment

Sedation scoring tools:

  • Are used to quantify the degree of sedation provided
  • Aim avoid over- or under-sedating patients
  • Include:
    • Ramsay Sedation Scale
    • Richmond Agitation Sedation Scale

EEG has also been trialled, but is limited by movement artifact and not yet made it into routine practice.

Richmond Agitation Sedation Scale

The RASS is a 10-point scale that grades patient arousal from:

  • +4: Combative
    Violent, with immediate danger to staff.
  • +3: Very agitated
    Pulls or removes indwelling devices.
  • +2: Agitated
    Non-purposeful, fights ventilator.
  • +1: Restless
    Anxious but not aggressive.
  • 0: Alert and calm
  • -1: Drowsy
    Sustained (>10s) awakening to voice.
  • -2: Light sedation
    Brief awakening to voice.
  • -3: Moderate sedation
    Movement or eye opening to voice.
  • -4: Deep sedation
    Movement or eye opening to pain.
  • -5: Unarousable
    No response to pain.

Principles

The goal of sedation is to achieve a controlled degree of sedation, specific to the needs of the patient, and based on the characteristics of the disease, patient, and therapy.

A large number of strategies have been described to achieve this, though there is little evidence supporting any one therapy:

  • No sedation
    ↑ Risk of accidental extubation and line removal without change in mortality.
  • Goal-directed sedation
    Sedatives freely adjusted by the beside nurse to attain the prescribed level of sedation.
    • Deep sedation
      • Indicated for certain specific disease states:
        • Severe T1RF
        • Hyperthermic emergencies
        • Super-refractory status epilepticus
        • ↑ ICP
      • Associated with:
        • Delayed extubation
        • ↑ Mortality
  • Patient-targeted sedation
    Consist of structured approach for:
    • Assessing pain and distress
    • Adjusting analgesia and sedation based on the algorithm
  • Daily interruption of sedation
    As goal-directed sedation, except aims to prevent excessive sedation by pausing sedation each day until the patient awakens or exhibits distress requiring recommencement.
    • Facilitate neurological assessment
    • Minimise accumulation of sedation
      This is more relevant to routine deep sedation, and targeting light (e.g. RASS >-2) sedation will limit this as well.
    • Are not necessary if light sedation is used
  • Intermittent sedation
    Intermittent administration of long-acting sedatives.
  • Analgo-sedation
    • Involves:
      • Commencing analgesia (classically opioid) until pain is controlled
      • Adding sedatives only if analgesia is inadequate
    • Benefits include possible ↓ mechanical ventilation duration, ICU length of stay, and VAP
    • Risks include possible ↑ self-extubation, myocardial ischaemia, and opioid withdrawal
  • Patient-controlled sedation

Practice

In general:

This framework outlines intravenous sedation and analgesia for tnhe above indications. More complex overlapping scenarios, such as severe opioid tolerance (e.g. long stay burns) or hyperactive delirium requiring antipsychotics are not covered here.

  • Deep sedation should be limited to specific indications
  • Most other patients should be sedated to RAAS of 0 to -2
  • High levels of sedation requirements may suggest another present pathology
    • If present, these should be managed separately
    • These include:
      • Pain
      • Delirium
      • Withdrawal
  • This may result certain patients receiving no sedation, typically those with:
    • Tracheostomy
    • Exceptional tube tolerance
  • Choice of drug is often based on institutional preference
    • Propofol is a common first-line agent
    • Dexmedetomidine:
      • Has analgesic and sedative properties
      • Provides conscious sedation
      • Is useful for weaning sedation in patients who:
        • Are emerging dangerously on propofol
        • Have controlled pain

Sedatives

Sedation infusions:

  • Propofol
    0-300mg/hr.
    • Easily titrated
    • ↓ Ventilation time compared to midazolam
    • May precipitate hypotension
    • Risk of hypertriglyceridaemia
      Should be taken account of in nutrition assessment.
    • Risk of propofol infusion syndrome
      • Paediatric with heart failure
      • Prolonged, high-dose infusions
  • Dexmedetomidine
    0-1.4μg/kg/min. Consider load of 1μg/kg over 10 minutes in well patients.
    • Analgo-sedative due to central α2-agonism
    • ↓ Opioid requirements
    • Minimal suppression of respiration
    • Major side effects include:
      • Bradyarrhythmia
      • Hyperthermia
  • Midazolam
    1-20mg/hr.
    • Wide dose requirement based on
      • Previous exposure
      • Age
      • Physiologic reserve
      • Organ function
      • Alcohol
      • Other drugs
    • Risk of accumulation in renal or hepatic failure
    • Significant dose ↓ with concurrent opioid infusions
  • Ketamine
    0.1-0.3mg/kg/hr.
    • Produces dissociative anaesthesia; with sedation, analgesia, and amnesia
    • Use limited predominantly by emergence phenomena
    • Indications include:
      • Asthma
      • Burns

Special:

  • Thiopentone
    • Very long CSHT limits general use
    • Immunosuppression
    • Essentially reserved for:
      • Intractable ↑ ICP
      • Status epilepticus
  • Volatile anaesthetics
    • Primarily used as bronchodilating sedation in severe asthma
    • General use is limited by:
      • Cost
        ↓ With modern devices that allow volatile to be recirculated in an ICU ventilator.
      • Complexity of running circle system
      • Occupational health risks

Analgesia

Opioids:

Common features of opioid infusions include:

  • High interindividual variability
  • Long duration of action due to:
    • Retained metabolites
    • Long CSHT
  • Constipation
    Aperients should be administered concurrently.
  • Tolerance
  • Fentanyl
  • Morphine
  • Remifentanil
    0.05-0.2μg/kg/min.
    • Short and reliable context-insensitive half-time
    • Provides tube tolerance and permits rapid sedation assessment
    • Risk of rebound hyperalgesia limits use to patients without much intrinsic pain

Key Studies

Dexmedetomidine:

  • Dexmedetomidine is a sedative that also produces biomimetic sleep

  • Patients may be more easily roused and appropriate when roused, which further ↑ utility of dexmedetomidine

  • MENDS-2 (2021)

    • 438 non-pregnant septic Americans without bradyarrhythmias requiring sedation for mechanical ventilation
    • Randomised, clinician (not nurse) blinded, multicentre (13) RCT
      Pharmacy prepared drugs in identical opaque bags, and nurses covered lines in opaque tubing.
    • 85% power to detect 1.5 day difference in days alive without delirium or coma
    • 80% power to detect a 12% (!!) ARR in mortality at 90 days, assuming 30% control mortality
    • Dexmedetomidine vs. propofol
      • Dexmedetomidine titrated by protocol between 0.15-1.5μg/kg/min
      • Propofol titrated by protocol between 5-50μg/kg/min
    • No change in primary outcomes
    • 90% of eligible patients excluded, predominantly by clinician or family

  • SPICE III (2019)

    • 4000 adult patients requiring mechanical ventilation
    • Unblinded, variable block RCT
    • 90% power for 4.5% ↓ 90 day mortality
    • Dexmedetomidine vs. usual care
      • Dexmedetomidine
        • Up to 1.5μg/kg/hr
        • 60% received propofol
      • Usual care
        • Other sedatives used
        • Dexmedetomidine as rescue if other agents required
    • No difference in primary outcome
    • Secondary outcomes showed no difference in cognitive decline or quality of life
    • Dexmedetomidine group had:
      • Better achievement of target sedation
      • 1 day less mechanical ventilation
      • ↑ Bradycardia, hypotension, and asystolic arrest (0.7% vs 0.1%)

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  2. Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021;384(15):1424-1436.
  3. Olsen HT, Nedergaard HK, Strøm T, et al. Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients. N Engl J Med. 2020;382(12):1103-1111. doi:10.1056/NEJMoa1906759
  4. Shehabi Y, Howe BD, Bellomo R, et al. Early Sedation with Dexmedetomidine in Critically Ill Patients. New England Journal of Medicine. 2019;380(26):2506-2517. doi:10.1056/NEJMoa1904710