Sedation

Levels of Sedation (American Society of Anesthesiologists, ASA) [ASA Website]

SEDATION


American Society of Anesthesiologists (ASA) Physical Status Classification

  • ASA 1: normal healthy patient
  • ASA 2: mild systemic disease
  • ASA 3: severe systemic disease
  • ASA 4: severe systemic disease that is constant threat to life
  • ASA 5: moribund patient who is not expected to survive without surgery
  • ASA 6: declared brain dead with plan for organ donation

Procedural Sedation

Indications for Procedural Sedation/Anxiolysis/Analgesia

  • Bone Marrow Biopsy (see Bone Marrow Biopsy, [[Bone Marrow Biopsy]])
  • Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])
  • Cardioversion for Atrial Fibrillation (see Atrial Fibrillation, [[Atrial Fibrillation]])
  • Dental Procedures
  • Endoscopy
  • Fine Needle Aspiration (FNA) of Mass/Lesion
  • Foreign Body Extraction: particularly in pediatric populations
  • Surgery

Relative Contraindications to Procedural Sedation

  • Older Age: older patients have higher rates of adverse events due to increased sensitivity to sedatives, medication interactions, and higher peak levels achieved with drugs
  • Comorbid Disease: patients with comorbid disease (ASA 3 or greater) have higher rates of adverse events

Agents

Barbiturates (see Barbiturates, [[Barbiturates]])

  • Methohexital (see Methohexital, [[Methohexital]])
    • Duration of Action: 10 min
    • Properties
      • Amnestic Effect
      • No Analgesic Effect
      • Sedation
    • Adverse Effects

Opiates

  • Alfentanil (Alfenta) (see Alfentanil, [[Alfentanil]])
  • Fentanyl (Sublimaze) (see Fentanyl, [[Fentanyl]])
    • Duration of Action: 2-3 min
    • Properties
      • Analgesic Effect
      • No Amnestic Effect
    • Administration
      • Use Decreased Dose in Combination with Other Agents
    • Adverse Effects
      • Minimal Histamine Release
      • Minimal Hypotension (see Hypotension, [[Hypotension]])
  • Remifentanil (Ultiva) (see Remifentanil, [[Remifentanil]])

Sedatives

  • Dexmedetomidine (Precedex) (see Dexmedetomidine, [[Dexmedetomidine]]): see below
  • Etomidate (Amidate) (see Etomidate, [[Etomidate]])
    • Duration of Action: 5-15 min
    • Properties
      • No Analgesic Effect
      • Sedative Effect
    • Administration
      • Use Lower Dose in Elderly or Those with Renal/Hepatic Insufficiency
    • Adverse Effects
  • Ketamine (see Ketamine, [[Ketamine]]): see below
  • Ketamine + Propofol (“Ketofol”)
    • Administration: usually 0.5-0.75 mg/kg for each agent
    • Adverse Effects: may be decreased, as compared to using each agent alone
  • Lorazepam (Ativan) (see Lorazepam, [[Lorazepam]]): see below
  • Midazolam (Versed) (see Midazolam, [[Midazolam]]): see below
    • Administration
      • Use Decreased Dose in Combination with Other Agents
  • Nitrous Oxide (see Nitrous Oxide, [[Nitrous Oxide]])
  • Propofol (Diprivan) (see Propofol, [[Propofol]]): see below

Management of Procedural Sedation

Pre-Procedural Fasting

  • Clinical Efficacy: there is little evidence to support the practice of pre-procedural fasting
    • No Clear Evidence That There is an Association Between Fasting Time, Gastric Volume, Gastric pH, Depth of Sedation and the Risk of Aspiration
    • Endotracheal Intubation May Not Protect the Patient from Patient From Aspiration [MEDLINE] [MEDLINE]
      • Endotracheal intubation itself increases the risk of aspiration
  • Recommendations: despite the lack of evidence, it is recommended to use the same fasting requirements for procedural sedation as for general anesthesia [MEDLINE]
    • Usual Protocol for Fasting Pre-Procedure
      • No Clear Liquids for 2 hrs Pre-Preprocedure
      • No Cow’s Milk or Solid Foods for 6 hrs Pre-Procedure
    • In the Case of Emergent Procedures, Consideration Should Be Given to Delaying the Procedure If the Patient Has Not Been Fasting: this is especially true in patients with increased risk of aspiration

Considerations Related to Procedural Sedation in Elderly Patients and Patients with Comorbid Disease

  • Giver Lower Starting Doses of Medications
  • Use Slower Rates of Medication Administration
  • Use Longer Intervals Between Repeat Doses

Considerations for Procedural Sedation in the Pregnant Patients

  • Pre-Procedural Medications to Increase Gastroesophageal Sphincter Tone and Decrease Gastric Volume: may reduce the risk of vomiting and aspiration
  • Pre-Procedural Medications to Decrease Gastric Acidity: may reduce the risk of vomiting and aspiration
  • Pre-Procedural Hydration and Left Lateral Displacement of Uterus (In Late 2nd-3rd Trimester): decreases the risk of hypotension, uteroplacental insufficiency, and fetal hypoxemia
  • Supplemental Oxygen (see Oxygen, [[Oxygen]]): recommended (due to decreased functional residual capacity present in pregnancy, which may result in maternal hypoxemia)

Avoidance of Deep Sedation

  • Clinical Efficacy
    • No Evidence Indicates That Deeper Levels of Sedation Increase the Risk of Aspiration [MEDLINE]: however, lighter sedation may allow the patient to better protect their airway during the procedure (decreasing the risk of aspiration)

Performance of the Procedure Under General Anesthesia

  • Clinical Efficacy
    • Performing the Procedure Under General Anesthesia Has Not Been Proven to Decrease the Risk of Aspiration [MEDLINE] [MEDLINE]

Supplemental Oxygen (see Oxygen, [[Oxygen]])

  • Recommended During Procedural Sedation to Prevent Hypoventilation-Associated Hypoxemia: with pulse oximetry
    • However, Supplemental Oxygen at Low Concentrations Does Not Reliably Prevent Hypoxemia and May Delay Detection of Respiratory Depression (If End-Tidal CO2 Monitor is Not Being Used): due to the fact that SaO2 may not decrease until a significant prolonged period of hypoventilation or apnea has occurred

End-Tidal CO2 Monitoring (see Capnography, [[Capnography]])

  • Recommended During Procedural Sedation to Monitor for Hypercapnia: EtCO2 values correlate closely with arterial pCO2 values and provide early evidence of hypoventilation or apnea

Other Measures

  • Bispectral Analysis Monitoring (BIS): does not appear to be useful for monitoring the depth of procedural sedation
    • Originally developed to monitor the level of general anesthesia
  • Pre-Procedural Antacids/Motility Agents: no clinical benefit -> not recommended

Adverse Effects of Procedural Sedation

  • Aspiration (see Aspiration Pneumonia, [[Aspiration Pneumonia]])
    • Epidemiology: incidence of 1.2 per 1000 sedations [MEDLINE]
    • Risk Factors for Aspiration
      • Depressed Mental Status
      • Emergent Procedure: typically related to full stomach
      • Esophageal Reflux
        • Bowel Obstruction
        • Hiatal Hernia
      • Extremes of Age (<6 mo Old or >70 y/o)
      • Severe Systemic Disease (ASA 3 or Greater)
  • Cardiovascular Instability
  • Emergence Reactions
  • Inadequate Sedation Preventing Completion of the Procedure
  • Laryngospasm (see Laryngospasm, [[Laryngospasm]])
  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): nausea/vomiting occurs in approximately 5% of patients undergoing procedural sedation
    • Epidemiology: incidence of 16.4 per 1000 sedations [MEDLINE]
      • Incidence of Nausea/Vomiting May Be Higher When Opiates are Used
    • Prophylactic Anti-Emetics: may be useful
  • Need for Intubation
  • Respiratory Depression with Hypoxemia/Hypercapnia (see Acute Hypoventilation, [[Acute Hypoventilation]])
    • Epidemiology: hypoxemia is the most common adverse event with procedural sedation with an incidence of 40.2 per 1000 sedations [MEDLINE]
    • Reversal Agents
      • Flumazenil (Romazicon) (see Flumazenil, [[Flumazenil]]): to reverse the effects of benzodiazepines
      • Naloxone (Narcan) (see Naloxone, [[Naloxone]]): to reverse the effects of opiates

Intensive Care Unit Sedation

Indications for Sedation in the Intensive Care Unit

  • Facilitation of Measurement of Lung Compliance
  • Prevent Disconnection of Life-Sustaining Therapy
    • Prevention of Extubation
    • Prevention of Removal of Arterial Line
    • Prevention of Removal of Central Venous Catheter
    • Prevention of Removal of Nasogastric Tube
  • Promotion of Patient-Ventilator Synchrony
  • Reduction in the Work of Breathing
  • To Allow the Use of Rescue Therapies: such as mechanical ventilation (especially for high frequency oscillation ventilation), etc

Agents

Dexmedetomidine (Precedex) (see Dexmedetomidine, [[Dexmedetomidine]])

  • Pharmacology: α2-Adrenergic Receptor Agonist (see α2-Adrenergic Receptor Agonists, [[α2-Adrenergic Receptor Agonists]])
    • Similar to Clonidine (see Clonidine, [[Clonidine]])
    • Duration of Action: xxx
    • Half-Life (Terminal Elimination): approximately 2 hrs
    • Use Beyond 24 Hours: associated with tachyphylaxis and dose-related increase in adverse reactions
  • Properties
    • Analgesic Effect
    • Anxiolytic Effect
    • Sedative Effect
    • Sympatholytic Effect
    • No Significant Respiratory Depression
  • Adverse Effects

Ketamine (see Ketamine, [[Ketamine]])

  • Pharmacology
    • Duration of Action: 5-20 min
  • Properties
    • Amnestic Effect (see Amnesia, [[Amnesia]])
    • Analgesic Effect
    • Dissociative Sedative Effect
    • Does Not Inhibit Protective Reflexes
    • Increased Circulating Norepinephrine
    • Minimal Cardiorespiratory Depression
  • Adverse Effects
    • Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])
    • Arrhythmias: occurs in some cases
    • Bradycardia: occurs in some cases
    • Diplopia (see Diplopia, [[Diplopia]]): may occur in some cases
    • Emergence Reactions: occurs in 12% of cases
      • Clinical: delirium, hallucinations, irrational behavior, etc
    • Enhanced Pressor Response: may occur with rapid administration
    • Fasciculations (see Fasciculations, [[Fasciculations]]): may occur in some cases
    • Hypertension (see Hypertension, [[Hypertension]]): typically occurs shortly after injection (and returns to normal within 15 min)
    • Hyporeflexia (see Hyporeflexia, [[Hyporeflexia]]): may occur in some cases
    • Hypotension (see Hypotension, [[Hypotension]]): occurs in some cases
    • Increased Cerebrospinal Fluid Pressure: may occur in some cases
    • Increased Intraocular Pressure: may occur in some cases
    • Laryngospasm (see Laryngospasm, [[Laryngospasm]])
    • Local Injection Site Pain: has been reported
    • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): usually not severe or prolonged
    • Nystagmus (see Nystagmus, [[Nystagmus]]): may occur in some cases
    • Respiratory Depression (see Acute Hypoventilation, [[Acute Hypoventilation]]): may occur with rapid administration or overdosage
    • Sympathetic Stimulation
    • Sialorrhea (Hypersalivation) (see Sialorrhea, [[Sialorrhea]])
    • Sinus Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]])
    • Tonic-Clonic Movements (Seizure-Like): may occur in some cases (due to enhanced muscle tone)
    • Transient Erythema/Morbilliform Rash: has been reported

Lorazepam (Ativan) (see Lorazepam, [[Lorazepam]])

  • Pharmacology: longer-acting benzodiazepine which has no active metabolites (see Benzodiazepines, [[Benzodiazepines]])
    • Lorazepam is poorly soluble in water: requires both the use of a propylene glycol diluent and large volumes to deliver
  • Properties
    • Amnestic Effect (see Amnesia, [[Amnesia]])
    • Sedative Effect
  • Adverse Effects

Midazolam (Versed) (see Midazolam, [[Midazolam]])

  • Pharmacology: benzodiazepine (see Benzodiazepines, [[Benzodiazepines]])
    • Onset: slow (requires gradual initiation)
    • Duration: 10-40 min (prolonged effect in elderly, obese, or those with impaired hepatic function)
    • Lipophilic: rapidly crosses the blood brain barrier -> may have prolonged duration of action and elimination when given as continuous infusion
  • Properties
    • Amnestic Effect (see Amnesia, [[Amnesia]])
    • Anxiolytic Effect
    • Sedative Effect
    • No Analgesia
  • Adverse Effects

Propofol (Diprivan) (see Propofol, [[Propofol]])

  • Pharmacology
    • Onset: rapid
    • Duration of Action: 5 min
  • Properties
    • Amnestic Effect (see Amnesia, [[Amnesia]])
    • Anti-Emetic Effect
    • Anxiolytic Effect
    • Sedative Effect
    • No Analgesic Effect
    • Large Lipid Load: requiring adjustment of enteral/parenteral nutritional support
  • Administration
    • Decrease Dose in Elderly by 20%
    • Slow Administration in Elderly
  • Adverse Effects

Clinical Efficacy

  • Dexmedetomidine (Precedex) Compared to Lorazepam (Ativan) (2007) (see Dexmedetomidine, [[Dexmedetomidine]] and Lorazepam, [[Lorazepam]]) [MEDLINE]
    • Dexmedetomidine Resulted in More Days Alive Without Delirium/Coma and More Time at the Target Level of Sedation
  • Dexmedetomidine (Precedex) Compared to Midazolam (Versed) (2009) (see Dexmedetomidine, [[Dexmedetomidine]] and Midazolam, [[Midazolam]]) [MEDLINE]
    • Dexmedetomidine is Similarly Effective for Sedation, as Compared to Midazolam
    • Dexmedetomidine Shortened the Time to Extubation, as Compared to Midazolam
    • Dexmedetomidine was Associated with Less Delirium, as Compared to Midazolam
    • Dexmedetomidine was Associated with Less Tachycardia/Hypotension, but More Bradycardia, as Compared to Midazolam
  • Dexmedetomidine (Precedex) Compared to Midazolam (Versed) (2010) (see Dexmedetomidine, [[Dexmedetomidine]] and Midazolam, [[Midazolam]]) [MEDLINE]
    • Dexmedetomidine Resulted in Less Cost in the ICU, as Compared to Midazolam: due to decreased length of ICU stay and decreased ventilator days
  • MIDEX and PRODEX Trials: Dexmedetomidine (Precedex) Compared to Midazolam (Versed) and Propofol (Diprivan) (2012) (see Dexmedetomidine, [[Dexmedetomidine]], Midazolam, [[Midazolam]], and Propofol, [[Propofol]]) [MEDLINE]
    • General Comments: data from randomized MIDEX (Midazolam vs. Dexmedetomidine) and PRODEX (Propofol vs. Dexmedetomidine) trials
    • Dexmedetomidine was Equivalent in Maintaining Light-Moderate Sedation
    • Dexmedetomidine Decreased the Duration of Mechanical Ventilation, as Compared to Midazolam (But Not When Compared to Propofol)
    • Dexmedetomidine Improved Patients’ Ability to Communicate Pain, as Compared with Midazolam and Propofol
    • Dexmedetomidine Demonstrated More Adverse Effects (Bradycardia/Hypotension), as Compared with Midazolam and Propofol
    • In the First 24 hrs of PRODEX Trial, Discontinuation of Dexmedetomidine was More Frequent Due to Lack of Efficacy: this suggests that adequate sedation may not be possible in all patients with dexmedetomidine alone (and it is likely that dexmedetomidine is not equivalent to propofol)
  • Propofol (Diprivan) Compared to Midazolam/Lorazepam (2014) (see Propofol, [[Propofol]], Midazolam, [[Midazolam]], and Lorazepam, [[Lorazepam]]) [MEDLINE]
    • Propofol Decreased Mortality Rate, as Compared to Benzodiazepines (Midazolam/Lorazepam)
    • Propofol Increased Probability of ICU Discarge at 28 Days, as Compared to Benzodiazepines (Midazolam/Lorazepam)
    • Propofol Decreased Ventilator Days at 28 Days, as Compared to Benzodiazepines (Midazolam/Lorazepam)
  • Dexmedetomidine (Precedex) to Lessen ICU Agitation (DahLIA) Trial (JAMA, 2016): Dexmedetomidine Compared to Placebo in Agitated Delirium in Mechanically-Ventilated Patients in the Intensive Care Unit (see Dexmedetomidine, [[Dexmedetomidine]]) [MEDLINE]
    • Dexmedetomidine Increased Ventilator-Free Hours at 7 Days, as Compared to Usual Care
    • Dexmedetomidine Decreased Time to Extubation and Accelerated Resolution of Delirium

Minimization of Sedation/Daily “Sedation Vacation”

Benefits of Minimization of Sedation/Daily “Sedation Vacation”

Clinical Efficacy

  • Studies Supporting the Performance of Paired Daily Sedation Vacation and Spontaneous Breathing Trials (SBT’s) (see Ventilator Weaning, [[Ventilator Weaning]])
    • Effect of Daily Sedation Vacation and Spontaneous Breathing Trials (NEJM, 1996) [MEDLINE]: daily spontaneous breathing trials decrease the duration of mechanical ventilation, decrease the cost of intensive care, and decrease complication rates
    • Awakening and Breathing Controlled (ABC) Trial (Lancet, 2008) [MEDLINE]: paired daily sedation vacation and spontaneous breathing trial decreases duration of mechanical ventilation, decreases ICU/hospital length of stay, and decreases mortality rate
    • Study of Standardized Weaning Protocols from Mechanical Ventilation (Cochrane Database Syst Rev, 2014) [MEDLINE]: standardized weaning protocols decrease duration of mechanical ventilation, weaning duration, and ICU length of stay
  • Other Studies
    • Australian/New Zealand SPICE Study (Am J Respir Crit Care Med, 2012) [MEDLINE]: evaluated ventilation time, sedation intensity using Richmond Agitation Sedation Scale (RASS), delirium, and mortality
      • Early Sedation Depth (Deep Sedation Within 4 hrs of Intubation) Predicted Delayed Extubation, Increased Hospital Mortality, and Increased 180-Day Mortality
        • However, 54.6% of the patient population was receiving midazolam at the first assessment point of 4 hrs (with 56.6% receiving propofol and 18.3% receiving both midazolam and propofol)
      • Early Sedation Depth Had No Effect on Delirium Occurring After 48 hrs

Continuous Sedation Infusion

  • Provides more constant level of sedation than intermittent bolus dosing and may increase patient comfort
  • Increases ventilator days and ICU length of stay
  • May limit the clinician’s ability to distinguish changes in mental status (perhaps prompting the increased use of diagnostic studies to rule out neurologic injury)

References

Procedural Sedation

  • Pulmonary aspiration of gastric contents in anaesthesia. Br J Anaesth. 1999;83(3):453 [MEDLINE]
  • Practice guidelines for sedation and analgesia by non-anesthesiologists. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Anesthesiology. 2002;96(4):1004 [MEDLINE]
  • Side effects of opioids during short-term administration: effect of age, gender, and race. Clin Pharmacol Ther. 2003;74(2):102 [MEDLINE]
  • Procedural sedation and analgesia in the emergency department: what are the risks? Emerg Med Clin North Am. 2005;23(2):551 [MEDLINE]
  • Preoperative fasting for preventing perioperative complications in children. Cochrane Database Syst Rev. 2005 [MEDLINE]
  • Pre-operative fasting guidelines: an update. Task Force on Scandinavian Pre-operative Fasting Guidelines, Clinical Practice Committee Scandinavian Society of Anaesthesiology and Intensive Care Medicine). Acta Anaesthesiol Scand. 2005;49(8):1041 [MEDLINE]
  • The incidence and outcome of perioperative pulmonary aspiration in a university hospital: a 4-year retrospective analysis. Anesth Analg. 2006;103(4):941 [MEDLINE]
  • Aspiration pneumonitis requiring intubation after procedural sedation and analgesia: a case report. Ann Emerg Med. 2007;49(4):462 [MEDLINE]
  • Fasting and emergency department procedural sedation and analgesia: a consensus-based clinical practice advisory. Ann Emerg Med. 2007;49(4):454 [MEDLINE]
  • American College of Chest Physicians Consensus Statement on the Use of Topical Anesthesia, Analgesia, and Sedation During Flexible Bronchoscopy in Adult Patients. Chest 2011; 140(5):1342–1350 [MEDLINE]
  • Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014 Feb;63(2):247-58.e18. doi: 10.1016/j.annemergmed.2013.10.015 [MEDLINE]
  • The use of propofol for procedural sedation in emergency departments. Cochrane Database Syst Rev. 2015 Jul 29;7:CD007399. doi: 10.1002/14651858.CD007399.pub2 [MEDLINE]
  • Incidence of Adverse Events in Adults Undergoing Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis. Acad Emerg Med. 2016 Feb;23(2):119-34. doi: 10.1111/acem.12875. Epub 2016 Jan 22 [MEDLINE]

Intensive Care Unit Sedation

  • Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Crit Care Med. 1995;23:1596-1600
  • Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335:1864-1869 [MEDLINE]
  • The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest 1998; 114:541-548
  • Sedation, where are we now? Intensive Care Med 1999; 25:137-139
  • Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342:1471-1477 [MEDLINE]
  • Hyperlactatemia, increased osmolar gap, and renal dysfunction during continuous lorazepam infusion. Crit Care Med. 2000;28:1631-1634
  • Short-term lorazepam infusion and concern for propylene glycol toxicity. Pharmacotherapy 2001; 21:1140
  • Severe hyperosmolar metabolic acidosis due to a large dose of intravenous lorazepam. N Engl J Med 2002; 346:1253
  • The long-term psychological effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med. 2003;168:1457-1461 [MEDLINE]
  • Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med. 2004;32:1272-1276 [MEDLINE]
  • Dexmedetomidine a novel analgesic with palliative medicine potential. J Pain and Palliative Care Pharmacotherapy 2006; 20 (2): 23–7. doi:10.1080/J354v20n02_05 [MEDLINE]
  • Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults. Crit Care Med 2004; 32:1709-1714
  • Propofol infusion syndrome. Anaesthesia. 2007;62:690-701
  • Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial”. JAMA 2007; 298 (22): 2644–53 [MEDLINE]
  • Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans. J Am Coll Cardiol 2007; 50 (7): 626–33. doi:10.1016/j.jacc.2007.03.060 [MEDLINE]
  • Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008 Jan 12;371(9607):126-34 [MEDLINE]
  • Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial”. JAMA 2009; 301 (5): 489–99 [MEDLINE]
  • Sedation Management in Australian and New Zealand Intensive Care Units: Doctors’ and Nurses’ Practices and Opinions”. Am J Crit Care 2009; 19 (3): 285–95 [MEDLINE]
  • A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit. Crit Care Med 2010; 38 (2): 497–503 [MEDLINE]
  • Role of α2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 2011 May;45(5):649-57. doi: 10.1345/aph.1P575. Epub 2011 Apr 26 [MEDLINE]
  • Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 2012 May 23;2(1):12. doi: 10.1186/2110-5820-2-12 [MEDLINE]
  • SPICE Study. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients.  Am J Respir Crit Care Med  October 15, 2012; 186(8):724-731 [MEDLINE]
  • MIDEX and PRODEX Trials: Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60 [MEDLINE]
  • American College of Critical Care Medicine: Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013, 41:263-306 [MEDLINE]
  • Sedative choice: a critical decision. Am J Respir Crit Care Med 2014;189(11):1295-1297 [MEDLINE]
  • Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care Med 2014;189(11):1383-1394 [MEDLINE]
  • American Society of Anesthesiologists (ASA) Guidelines [ASA Website]
  • Protocolized versus non-protocolized weaning for reducing the duration of mechanical ventilation in critically ill adult patients. Cochrane Database Syst Rev. 2014 Nov 6;11:CD006904. doi: 10.1002/14651858.CD006904.pub3 [MEDLINE]
  • Ketamine for continuous sedation of mechanically ventilated patients. J Emerg Trauma Shock. 2015 Jan-Mar;8(1):11-5. doi: 10.4103/0974-2700.145414 [MEDLINE]
  • Clinical effectiveness of a sedation protocol minimizing benzodiazepine infusions and favoring early dexmedetomidine: a before-after study. Crit Care. 2015 Apr 2;19:136. doi: 10.1186/s13054-015-0874-0 [MEDLINE]
  • DahLIA Trial: Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium. JAMA. 2016 Mar 15. doi: 10.1001/jama.2016.2707 [MEDLINE]