Post-Intubation Sedation and Analgesia

Aka: Post-Intubation Sedation and Analgesia, Sedation and Analgesia in Ventilated Patients, Sedation and Analgesia in Intensive Care, Insomnia Management in Critical Care

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II. Precautions

  1. Balance adequate pain and sedation with over-sedation
    1. Inadequate treatment increases Energy Expenditure, Agitation and PTSD
    2. Excessive sedation delays Extubation and increases mortality
  2. Analgesia (e.g. Fentanyl) should accompany sedation (e.g. Propofol) in intubated patients
    1. See Critical Care Pain Observation Tool (CPOT)
    2. Opioids are preferred Analgesics (e.g. Fentanyl, remifentanil, Morphine, Hydromorphone)
    3. First address pain, and then address sedation
      1. Most common memory of Critical Illness patients, is the memory of pain
      2. Pain from ET Tube, suctioning, procedures
    4. Concurrent analgesia relieves pain and decreases Ventilator bucking
    5. Concurrent analgesia allows for less Deep Sedation and reduced secondary Delirium
    6. Cases in which Deep Sedation is initial goal
      1. Increased Intracranial Pressure
      2. Severe Respiratory Failure
      3. Status Epilepticus
      4. Rapid Sequence Intubation
        1. Paralytic Agents do not sedate!
        2. Ensure adequate sedation while paralyzed (e.g. Rocuronium)
        3. Patient may otherwise awaken, aware of ET Tube, but paralyzed (torture)
  3. Propofol and Dexmedetomidine are preferred Sedatives
    1. Benzodiazepines (e.g. Lorazepam, Midazolam) in contrast result in longer intubation and ICU duration
    2. Fraser (2013) Crit Care Med 41(9 suppl 1): 830-8 [PubMed]
  4. Avoid longer-acting paralytics in general
    1. May be useful to reduce shivering in Induced Hypothermia protocol
    2. Do not use without sedation and Analgesics
    3. Vecuronium (Norcuron) 0.1 mg/kg IV
    4. Pancuronium (Pavulon) 0.1 mg/kg IV
  5. Post-Intubation Sedation and Analgesia is often inadequate
    1. Study of 10 interviewed patients, 5 patients could recollect their emergency intubation (including associated pain)
      1. Kinmball (2011) West J Emerg Med 12(4): 3655-7 [PubMed]
    2. Long-acting paralytics (recuronium) are associated with longer delays, too low dose of sedation and analgesia
      1. Paralysis outlasts induction agent leaving only indirect external cues (e.g. Sinus Tachycardia)
      2. Critical to have adequate analgesia and sedation started from the time of intubation
      3. Johnson (2015) J Emerg Med 49(1):43-9 +PMID:25797938 [PubMed]
      4. Korinek (2014) Eur J Emerg Med 21(3): 206-11 [PubMed]
    3. Sedation and analgesia is inconsistently used and at inadequate doses
      1. Bunomo (2008) Am J Emerg Med 26(4): 469-72 [PubMed]
      2. Kendrick (2009) Pediatr Emerg Care 25(6): 393-6 [PubMed]

III. Approach: Default Strategies

  1. Fentanyl with Propofol
    1. Precautions
      1. See Propofol Infusion Syndrome
      2. Hypotension risk (esp. with Propofol)
        1. Fluid boluses as needed
        2. May require initial Norepinephrine
    2. Target
      1. Richmond Agitation and Sedation Scale (RASS): Alert and calm (0) to drowsy (-1)
      2. Modify with deeper sedation for Delirium or similar indications
    3. Protocol: Analgesia AND Sedation
      1. Approach: Lead with analgesia and titrate sedation as needed
      2. Analgesia (primary medication)
        1. Choose one Analgesic (e.g. Fentanyl, hydomorphone, Morphine)
          1. Dose immediately after intubation
          2. Reassess every 1-2 hours for additional doses
        2. Fentanyl infusion is most commonly used
          1. Give Fentanyl bolus, Hydromorphone bolus or Morphine bolus until infusion Running
          2. However, losing favor due to adverse effects and recommended to wean to other agents
      3. Sedation (added to the analgesia, wean as able)
        1. Choose one Sedative (e.g. Propofol, Ketamine)
        2. Propofol is most commonly used (however, risk of Propofol Infusion Syndrome)
        3. Start immediately after intubation
  2. Special Cohort Agent Selection
    1. Neuro ICU (e.g. head injured patient)
      1. Propofol and Fentanyl
      2. Exercise caution with Propofol induced Hypotension (worse neurologic outcomes)
    2. Status Epilepticus
      1. Propofol
      2. Ketamine or Dexmedetomidine may be considered
    3. Alcohol Withdrawal
      1. Benzodiazepines
      2. Propofol
      3. Dexmedetomidine (Precedex)
    4. Hypotensive medical patient
      1. Fentanyl
      2. Benzodiazepine
      3. Ketamine
      4. Once Hypotension is corrected with fluid Resuscitation and Vasopressors, Propofol may be used

IV. Medications: Analgesics

  1. See Acute Pain Management
  2. See Opioid Analgesic
  3. See Regional Anesthesia
  4. Analgesics are the core drugs in this regimen
    1. Controlling post-intubation pain is a critical post-intubation task
    2. With adequate Analgesic use, sedation doses may be minimal
    3. However, Analgesics should specifically target pain and should not be used for sedation
      1. See Critical Care Pain Observation Tool (CPOT)
    4. Most Sedatives are not Analgesics
      1. Exceptions: Ketamine, Dexmedetomidine
    5. Fentanyl or Remifentanil
      1. Preferred first-line agents (quick onset, short duration and less hemodynamic effects)
  5. Fentanyl (preferred initial Analgesic)
    1. Bolus
      1. Fentanyl 0.35 to 0.5 mcg/kg (or 50 mcg) IV as needed until patient appears comfortable
      2. Onset in 1 to 2 minutes
      3. Duration 30 to 60 minutes
    2. Infusion
      1. Typical dosing: 25-50 mcg/hour
        1. Fentanyl 25 mcg/h is equivalent to Oxycodone 120 mg per day
      2. High dose: 1 mcg/kg/hour (or ~70 mcg/hour, up to 250 mcg/hour)
        1. Risk of Opioid-Induced Hyperalgesia
    3. May be administered in hypotensive patients
      1. Fentanyl is among the most hemodynamically stable Opioids
      2. Manage Hypotension with standard fluid boluses, Vasopressors
    4. Precautions
      1. Risk of Opioid tolerance within days of continuous use with risk of Opioid Withdrawal on stopping
      2. Attempt to wean dose on each day of infusion, and switch when able to other agents (see below)
  6. Alternative Opioids to Fentanyl
    1. Remifentanil (Ultiva)
      1. Bolus: 1 to 1.5 mcg/kg IV
        1. Onset in 1 to 3 minutes
        2. Duration 3 to 10 minutes (much shorter than Fentanyl)
      2. Infusion: 0.25 mcg to 0.5 mcg/kg/min
      3. Safe in Renal Failure or hepatic failure
    2. Hydromorphone (Dilaudid)
      1. Bolus: 1 mg IV initially, then 0.5 mg every 1 hour as needed (range 0.5 to 2 mg)
        1. Subsequent lower doses of 0.2 to 0.4 mg every 1 hour are often effective
        2. Onset 5 to 15 min
        3. Duration 3 to 4 hours
      2. Infusion: 0.5 to 3 mg/hour
      3. Preferred Opioid in end-stage renal disease
        1. Hydromorphone is primarily metabolized in the liver
    3. Morphine
      1. Bolus: 0.1 mg/kg up to 8-10 mg every 2 hours as needed
        1. Subsequent lower doses of 2 to 4 mg every 1 hour are often effective
        2. Onset in 5 to 10 min
        3. Duration 3 to 5 hours
      2. Infusion: 2 to 30 mg/hour (up to 40 mg/hour)
      3. AVOID in Hypotension (use Fentanyl or Remifentanil instead)
      4. AVOID in hepatic failure due to risk of accumulation (use Remifentanil instead)
      5. AVOID in Renal Failure (use Hydromorphone or Remifentanil instead)
    4. Oral Opioids (via Enteral Tube in stable patients with moderate persistent pain)
      1. Oxycodone 5-10 mg every 4-6 hours as needed
      2. Hydromorphone (Dilaudid) 2-4 mg every 4-6 hours
      3. Morphine Sulfate Immediate Release (MSIR) 15 to 30 mg PO q4 hours
  7. Non-Opioid Analgesics
    1. Acetaminophen
      1. Consider scheduled dosing every 6 hours, via Rectum or Enteral Tube
      2. Safe in most patients, aside from acute Hepatic Injury
      3. Typical dosing: 1000 mg every 6 hours (max 4000 mg/day)
        1. Reduce to 650 mg every 8 hours in Chronic Liver Disease or Alcohol Abuse (max 2000 mg/day)
    2. Ketamine
      1. Moderate analgesia (and also used for sedation - see below)
      2. Decreases Opioid requirements, tolerance and adverse effects (Opioid-Induced Hyperalgesia, Vomiting)
      3. Dosing: 0.1 to 0.3 mg/kg/hour (sub-dissociative dose)
        1. Exercise caution above 0.2 to 0.3 mg/kg (risk of Hallucinations, flashbacks, Agitation)
        2. Stop infusion for 1 hour if psychotropic effects, and restart infusion at 0.1 mg/kg/h
      4. Consider with adjunctive agents that potentiate Ketamine effects (avoid in Hypotension, Bradycardia)
        1. Dexmedetomidine or Precedex
        2. Clonidine
  8. Agents to avoid
    1. Avoid Tramadol
      1. See Tramadol
      2. Weak Opioid with risk of Serotonin Syndrome, Delirium and Seizures
    2. Avoid NSAIDs
      1. See Nephrotoxicity due to NSAIDs
      2. See NSAID Gastrointestinal Adverse Effects (Peptic Ulcer Disease)

V. Medications: Sedation

  1. See Procedural Sedation and Analgesia
  2. Targets
    1. Richmond Agitation and Sedation Scale (RASS)
      1. Goal RASS: Alert and calm (0) to drowsy (-1) or lightly sedated (-2)
    2. Critical Care Pain Observation Tool (CPOT)
      1. Target analgesia first (see above), then sedation
      2. Goal CPOT <=2
  3. Propofol (typically preferred)
    1. Most common post-intubation Sedative (esp. Status Epilepticus, Alcohol Withdrawal, CNS condition)
    2. Offers no analgesia, and risk of Hypotension, Propofol Infusion Syndrome, Bacterial Infection
    3. Bolus (adults): 60 to 80 mg IV
      1. Lower doses (10 to 20 mg IV) may be effective
      2. Be ready with repeat boluses while starting Propofol infusion
      3. Onset in 10 to 30 seconds
    4. Infusion: 10-30 mcg/kg/min (low dose when used with Fentanyl)
      1. Less adverse effects (including Propofol Infusion Syndrome) with dosing <50 mcg/kg/min
      2. Infusion dosing as high as 50-100 mcg/kg/min may be needed in some cases
    5. Avoid in hemodynamically Unstable Patients refractory to adequate fluid Resuscitation, Vasopressors
      1. Consider Ketamine as an alternative in these cases
    6. Risk of Propofol Infusion Syndrome
      1. Especially in the young, septic, Trauma or those on Corticosteroids or Vasopressors
    7. Risk of Hypertriglyceridemia (and Acute Pancreatitis)
      1. Propofol is a lipid-based infusion that contains 1 kcal/ml
  4. Alternatives to Propofol
    1. Dexmedetomidine (Precedex)
      1. Central alpha agonist Sedative, with anxiolysis and Analgesic effects that is generic
      2. Indications
        1. Indicated in Ventilator Weaning (decreased Delirium, duration of Mechanical Ventilation)
        2. Used in Alcohol Withdrawal as Benzodiazepine adjunct, often in non-intubated patients
      3. Dosing
        1. Load: Start high dose infusion 1 to 1.4 mcg/kg/hour without bolus
          1. Decrease infusion rate in the first 30-60 minutes to maintenance dose
          2. Alternative to 0.5 to 1 mcg/kg bolus which may have higher adverse effects
        2. Maintenance: 0.2 to 0.7 mcg/kg/hour (up to 1.5 mcg/kg/hour)
      4. No respiratory depression
        1. Very effective in the Ventilator Weaning process (also reduces associated anxiety, Tachypnea)
      5. Use other agents (e.g. Propofol) in the first hour after intubation (delayed effect with Dexmedetomidine)
      6. Risk of Bradycardia and Hypotension, as Clonidine-like effect (avoid bolus dosing)
        1. Low dose Epinephrine infusion may be used to counter Dexmedetomidine effects if needed
      7. Risk of tolerance (within 4-5 days of starting)
        1. Results in less sedation and risk of withdrawal
        2. Transition to Clonidine if Dexmedetomidine tolerance develops
    2. Ketamine
      1. Dosing
        1. Bolus: 0.5 to 1 mg/kg (onset in 10 to 30 seconds)
        2. Infusion: 0.5 to 2 mg/kg/hour
      2. Mechanism
        1. Rapidly acting with short duration, Analgesic effects and raises Blood Pressure and Heart Rate
      3. Indications
        1. Sedation in hemodynamically Unstable Patients and peri-intubation (does not blunt respirations)
        2. Consider in Asthma or COPD exacerbation
        3. Consider in hemodynamically Unstable Patients
      4. Precautions
        1. Less standardized protocols for prolonged sedation with Ketamine (and unclear longterm safety data)
        2. Risk of Hallucinations, Delirium, Tachycardia
    3. Avoid Benzodiazepines as primary Sedatives (may be used for secondary adjuncts)
      1. Indications
        1. Status Epilepticus
        2. Continued chronic Benzodiazepines
        3. Alcohol Withdrawal
        4. Ketamine re-emergence
        5. Consider in hypotensive medical patients
      2. Precautions
        1. Associated with longer duration Mechanical Ventilation and hospital stays
        2. Associated with Delirium (increased risk with cummulative dosing)
          1. Pandharipande (2006) Anesthesiology 104(1):21-6 +PMID:1639485 [PubMed]
        3. Associated with longterm cognitive insult
        4. Effective only initially and transiently, and titration is difficult
      3. Dosing
        1. Midazolam 1-2 mg IV prn
        2. Lorazepam 1-2 mg IV prn
          1. Risk of Metabolic Acidosis due to Lactic Acidosis, Acute Kidney Injury (propylene glycol)

VI. Medications: Adjuncts for Agitation and Anxiety

  1. See Agitated Delirium
  2. See Agitation in Dementia
  3. Haloperidol
  4. Olanzapine
  5. Ketamine

VII. Management: Post-Intubation Paralysis (avoid in most cases)

  1. No longer routinely recommended due to Myopathy
    1. May be needed in hyperventilating patients with Breath Stacking
  2. Advantages
    1. Reduced oxygen demands
    2. Improved Metabolic Acidosis
    3. Reduced Barotrauma
  3. Indications
    1. Ventilator-patient desynchrony
    2. High peak airway pressure
    3. Failed response to sedation
    4. Therapeutic Hypothermia
  4. Complications
    1. Myopathy (exacerbated by Corticosteroids)
    2. Increased Deep Vein Thrombosis risk
    3. Unable to assess mental status
  5. Pearls
    1. Define lowest effective dose with nerve stimulator
    2. Hold infusion every 4-6 hours (avoids accumulation)
    3. Concurrent sedation is imperative (see below)
  6. References
    1. Cornwell (2003) UW New Therepeutics Lecture, Cable,WI

VIII. Management: Insomnia (and Delirium prevention)

  1. See Insomnia
  2. General measures
    1. Avoid sleep interruption (minimize lab testing, Blood Pressure cuff, examination overnight)
    2. Apply eye shades and ear plugs overnight
    3. Assist with daytime reorientation and activity (eye glasses, lighting, early mobilization)
  3. Medications
    1. Avoid Benzodiazepine and Nonbenzodiazepine Hypnotic Agent or Z-Drug (e.g. Zolpidem or Ambien)
    2. Melatonin 3 mg (or Ramelteon 8 mg) scheduled dosing at night
    3. Quetiapine 25-50 mg orally (or via Enteral Tube) in early evening
    4. Clonidine 0.2 to 0.3 mg in evening (avoid in Hypotension or Bradycardia)
    5. Dexmedetomidine with dose increased in evening and decreased significantly during daytime
    6. Trazadone (other agents are preferred)

IX. Resources

  1. Internet Book of Critical Care (EMCRIT.org)
    1. https://emcrit.org/ibcc/guide/

X. References

  1. Copeland and Mehta (2024) Crit Dec Emerg Med 33(9): 27-35
  2. Marino (2014) The ICU Book, p. 901-22
  3. Orman and Weingart in Herbert (2014) EM:Rap 14(4): 8-9
  4. Arora and Menchine in Herbert (2014) EM:Rap 14(9): 2-3
  5. Swaminathan and Weingart (2019) EM:Rap 19(3): 2-3

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