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 an increased risk of aspiration
Pre-Procedural Antacids/Motility Agents
Clinical Efficacy
No Clinical Benefit: not recommended
Pre-Procedural Sedation Assessment
American Society of Anesthesiologists (ASA) Physical Status Classification
ASA 1: Normal Healthy Patient
Examples
Varicose Veins in Otherwise Healthy Patient
ASA 2: Mild Systemic Disease That Does Not Impair Normal Activity
General Comments: Mallampati scoring is necessary to determine the pre-procedural difficulty of airway management in case sedation-related respiratory complications occur
Mallampati Airway Class/Score: assessed in upright patient with mouth wide open and tongue out -> allows assessment of oral size and anatomy of tongue and oropharynx
Class I: hard palate, soft palate, entire uvula, fauces, and pillars visible
Class II: hard palate, soft palate, part of uvula, and fauces visible
Class III: hard palate, soft palate, and base of uvula visible -> predicts difficult mask ventilation and difficult intubation
Class IV: only hard palate visible -> predicts difficult mask ventilation and difficult intubation
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): 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]
Recommendations
Despite Evidence, Lighter Sedation May Allow the Patient to Better Protect Their Airway During the Procedure (Decreasing the Risk of Aspiration)
Performance of Procedure Under General Anesthesia (see General Anesthesia)
Clinical Efficacy
Performing the Procedure Under General Anesthesia Has Not Been Proven to Decrease the Risk of Aspiration [MEDLINE] [MEDLINE]
Supplemental Oxygen is Recommended (in Conjunction with Pulse Oximetry) During Procedural Sedation to Prevent Hypoventilation-Associated Hypoxemia
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
Score = 1 (Restless): anxious, but movements not aggressive or vigorous
Score = 0 (Alert and Calm): alert and calm
Score = -1 (Drowsy): not fully alert, but sustained awakening (eye opening or eye contact) to voice (≥10 sec)
Score = -2 (Light Sedation): briefly awakens with eye contact to voice (<10 sec)
Score = -3 (Moderate Sedation): movement or eye opening to voice, but no eye contact
Score = -4 (Deep Sedation): no response to voice, but movement or eye opening with physical stimulation
Score = -5 (Cannot Be Aroused): no response to voice or physical stimulation
Riker Sedation-Agitation Scale (SAS)
Score = 7 (Dangerous Agitation): pulling at endotracheal tube, trying to remove catheters, climbing over bed rail, striking at staff, thrashing from side to side
Score = 6 (Very Agitated): requiring restraint and frequent verbal reminding of limits, biting endotracheal tube
Score = 5 (Agitated): anxious or physically agitated, calming at verbal instruction
Recommendations (Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit; 2013) [MEDLINE]
Richmond Agitation-Sedation Scale (RASS) and Riker Sedation-Agitation Scale (SAS) are Most Valid and Reliable Sedation Assessment Tools for the Measurement of Quality/Depth of Sedation in Adult ICU Patients (Grade B Recommendation)
Objective Measures of Brain Function are Not Recommended as the Primary Method of Assessment of Sedation in Non-Comatose, Non-Paralyzed Critically Ill Adult ICU Patients (Grade -1B Recommendation)
Objective Measures of Brain Function are Suggested as an Adjunct Method of Assessment of Sedation in Critically Ill Adult ICU Patients Receiving Neuromuscular Blockade (Grade +2B Recommendation)
EEG Monitoring is Recommended to Monitor Non-Convulsive Seizure Activity in Adult ICU Patients with Known/Suspected Seizures or to Titrate Anticonvulsants to Achieve Burst Suppression in Patients with Elevated Intracranial Pressure (Grade +1A Recommendation)
Association of Sedation Use with Physical Restraint Use
Studies
Use of Physical Restraints in the ICU is Associated with Sedative Use, Analgesic Use, Anti-Psychotic Drug Use, Agitation, Heavy Sedation, and Occurrence of an Adverse Event (Crit Care, 2014) [MEDLINE]: treatment characteristics predominantly predicted restraint use, as opposed to patient or hospital/ICU characteristics
Adrenal Suppression (see Adrenal Insufficiency): this side effect has created ongoing concern about the use of etomidate for induction for endotracheal intubation in critically ill patients
In the KETASED Multicenter, Randomized Trial of Etomidate vs Ketamine for Intubation of Acutely Ill Patients, Ketamine was a Safe Alternative to Etomidate for Endotracheal Intubation (Although the Percentage of Patients with Adrenal Insufficiency was Significantly Higher in the Etomidate Group) (Lancet, 2009) [MEDLINE]
In a Propensity Score Analysis of Etomidate in Patients with Septic Shock Treated with Hydrocortisone, Etomidate Did Not Impact Life-Threatening Complications Following Intubation, But When Associated with Hydrocortisone, it Also Did Not Worsen Outcome (Crit Care, 2012) [MEDLINE]
In Retrospective Trauma Study Using Propofol as an Induction Agent for Rapid Sequence Intubation, Propofol Did Not Result in Hypotension (Mean Dose: 127 ± 5 mg), as Compared to Etomidate (Mean Dose: 21 ± 6 mg) (Eur J Trauma Emerg Surg, 2015) [MEDLINE]
In a Systematic Review and Meta-Analysis of Mostly Retrospective/Observational Studies of Single-Dose Etomidate for Endotracheal Intubation in Patients with Sepsis, Etomidate Did Not Increase the Mortality Rate (Chest, 2015) [MEDLINE]
In a Cochrane Database Systematic Review of Single-Dose Etomidate for Induction for Endotracheal Intubation, There was No Conclusive Evidence that Etomidate Increased the Mortality Rate or Healthcare Resource Utilization in Critically Ill Patients (But Did Increase the Risk of Adrenal Dysfunction and Multiorgan System Dysfunction by a Small Amount) (Cochrane Database Syst Rev, 2015) [MEDLINE]
In a Comparison of Etomidate and Ketamine for Induction During Rapid Sequence Intubation of Adult Trauma Patients, Patient-Centered Outcomes were Comparable for Either Agent (Ann Emerg Med, 2017) [MEDLINE]
In the KEEP PACE Randomized Trial of Ketamine/Propofol vs Decreased-Dose Etomidate for Induction Prior to Endotracheal Intubation of Critically Ill Patients, Ketamine/Propofol Admixture (0.5 mg/kg of Ketamine and Propofol Each) was Comparable to Decreased Dose Etomidate (0.15 mg/kg) in Terms of Maintaining Mean Arterial Blood Pressure, Use of Vasopressors, and Difficulty of Intubation (J Trauma Acute Care Surg, 2019) [MEDLINE]
Tonic-Clonic Movements (Seizure-Like): may occur in some cases (due to enhanced muscle tone)
Transient Erythema/Morbilliform Rash: has been reported
Clinical Efficacy
In the KETASED Multicenter, Randomized Trial of Etomidate vs Ketamine for Intubation of Acutely Ill Patients, Ketamine was a Safe Alternative to Etomidate for Endotracheal Intubation (Although the Percentage of Patients with Adrenal Insufficiency was Significantly Higher in the Etomidate Group) (Lancet, 2009) [MEDLINE]
In Small Case Series, Ketamine and Propofol (“Ketofol”) Can Be Used as Induction Agents for Intubation of Hemodynamically-Unstable Critically Ill Patients (Am J Case Rep, 2015) [MEDLINE]
In a Comparison of Etomidate and Ketamine for Induction During Rapid Sequence Intubation of Adult Trauma Patients, Patient-Centered Outcomes were Comparable for Either Agent (Ann Emerg Med, 2017) [MEDLINE]
In the KEEP PACE Randomized Trial of Ketamine/Propofol vs Decreased-Dose Etomidate for Induction Prior to Endotracheal Intubation of Critically Ill Patients, Ketamine/Propofol Admixture (0.5 mg/kg of Ketamine and Propofol Each) was Comparable to Decreased Dose Etomidate (0.15 mg/kg) in Terms of Maintaining Mean Arterial Blood Pressure, Use of Vasopressors, and Difficulty of Intubation ( J Trauma Acute Care Surg, 2019) [MEDLINE]
Study of the Safety of Propofol as an Induction Agent for Urgent Endotracheal Intubation in the ICU Demonstrated a Low Rate (4%) of Hypotension (J Intensive Care Med, 2015) [MEDLINE]
Protocol Used 0.5-1.0 mg/kg as the Initial Dose
Average Dose of Propofol: 99 mg (SD ± 7.39)
Concomitant Vasopressors were Used in 59% of Cases
In Retrospective Trauma Study Using Propofol as an Induction Agent for Rapid Sequence Intubation, Propofol Did Not Result in Hypotension (Mean Dose: 127 ± 5 mg), as Compared to Etomidate (Mean Dose: 21 ± 6 mg) (Eur J Trauma Emerg Surg, 2015) [MEDLINE]
In Small Case Series, Ketamine and Propofol (“Ketofol”) Can Be Used as Induction Agents for Intubation of Hemodynamically-Unstable Critically Ill Patients (Am J Case Rep, 2015) [MEDLINE]
In the KEEP PACE Randomized Trial of Ketamine/Propofol vs Decreased-Dose Etomidate for Induction Prior to Endotracheal Intubation of Critically Ill Patients, Ketamine/Propofol Admixture (0.5 mg/kg of Ketamine and Propofol Each) was Comparable to Decreased Dose Etomidate (0.15 mg/kg) in Terms of Maintaining Mean Arterial Blood Pressure, Use of Vasopressors, and Difficulty of Intubation ( J Trauma Acute Care Surg, 2019) [MEDLINE]
Clinical Utility: has been used as a sole sedative agent, due to its sedating properties
Trials Have Compared Remifentanil with Midazolam, Midazolam with Fentanyl, Fentanyl, and Morphine
Adverse Effects
xxxx
Comparative Clinical Efficacy Studies of Induction Medications for Endotracheal Intubation
Retrospective Trauma Study Using Propofol as an Induction Agent for Rapid Sequence Intubation (Eur J Trauma Emerg Surg, 2015) [MEDLINE]
Propofol Did Not Result in Hypotension (Mean Dose: 127 ± 5 mg), as Compared to Etomidate (Mean Dose: 21 ± 6 mg
Small Case Series Studying Combination Ketamine and Propofol (“Ketofol”) as Induction Agents for Endotracheal Intubation of Hemodynamically-Unstable Critically Ill Patients (Am J Case Rep, 2015) [MEDLINE]
Combination Ketamine and Propofol Can Be Used as Induction Agents for Endotracheal Intubation of Hemodynamically-Unstable Critically Ill Patients
KEEP PACE Randomized Trial of Ketamine/Propofol vs Etomidate for Induction Prior to Endotracheal Intubation of Critically Ill Patients ( J Trauma Acute Care Surg, 2019) [MEDLINE]: n = 160
Ketamine/Propofol Admixture (0.5 mg/kg of Ketamine and Propofol Each) was Comparable to Decreased Dose Etomidate (0.15 mg/kg) in Terms of Maintaining Mean Arterial Blood Pressure
No Difference in the Use of New-Onset Vasopressors or Difficulty of Intubation Between the Groups
For patients who had adrenal testing performed, more patients in the etomidate group developed immediate adrenal insufficiency (13 [81%] of 16 vs. 5 [38%] of 13, p = 0.027)
Comparative Clinical Efficacy Studies of Intensive Care Unit Sedation
Cohort Study of ICU Sedation and Risk of Delirium (Anesthesiology, 2006) [MEDLINE]
Lorazepam is an Independent Risk Factor for the Development of Delirium
Dexmedetomidine (Precedex) Compared to Lorazepam (Ativan) (JAMA, 2007) [MEDLINE]
Dexmedetomidine Resulted in More Days Alive Without Delirium/Coma and More Time at the Target Level of Sedation
Trial of Dexmedetomidine vs Haloperidol in Agitated Delirium in Mechanically Ventilated Patients (Crit Care, 2009) [MEDLINE]
Dexmedetomidine Decreased the Time to Extubation and ICU Length of Stay, As Compared to Haloperidol
Dexmedetomidine Decreased the Propofol Requirement
Dexmedetomidine (Precedex) Compared to Midazolam (Versed) (JAMA, 2009) [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) (Crit Care Med, 2010) [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) (JAMA, 2012) [MEDLINE]: 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
Rates of Anxiety/Agitation/Delirium were Lower with Dexmedetomidine than with Propofol, But the Rates were the Same Between Dexmedetomidine and Midazolam: CAM-ICU delirium rates assessed 48 hrs after sedation was stopped showed no differences between the groups
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)
Comparison of Non-Benzodiazepine Sedation (Dexmedetomidine, Propofol) vs Benzodiazepine Sedation in Mechanically Ventilated ICU Patients (Crit Care Med, 2013) [MEDLINE]
Use of Dexmedetomidine/Propofol-Based Sedation Regimen Decreased ICU Length of Stay and Duration of Mechanical Ventilation, as Compared to a Benzodiazepine-Based Regimen
Propofol (Diprivan) Compared to Midazolam/Lorazepam (Am J Respir Crit Care Med, 2014) [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 [MEDLINE]
Dexmedetomidine Increased Ventilator-Free Hours at 7 Days, as Compared to Usual Care
Dexmedetomidine Decreased Time to Extubation and Accelerated Resolution of Delirium
Meta-Analysis of Dexmedetomidine in ICU Sedation (Anaesth Crit Care Pain Med, 2016)[MEDLINE]
Dexmedetomidine was Associated with a 48 hr Reduction in ICU Length of Stay, Mechanical Ventilation Duration, and Duration of Delirium: despite significant heterogeneity among the studies
Dexmedetomidine was Associated with an Increased Risk of Bradycardia and Hypotension
Open-Label, Randomized SPICE III Trial of Early Dexmedetomidine (vs Propofol, Midazolam, or Other Sedatives) in Critically Ill Patients (NEJM, 2019)[MEDLINE]: n = 4,000
In a Modified Intention-to-Treat Analysis Involving 3,904 Patients, Any-Cause Mortality was 29.1% in the Dexmedetomidine Group and 29.1% in the Usual Care Group (Adjusted Risk Difference, 0.0%; 95% CI: -2.9 to 2.8)
An Ancillary Finding was that to Achieve the Prescribed Level of Sedation, Patients in the Dexmedetomidine Group Received Supplemental Propofol (64% of Patients), Midazolam (3%), or Both (7%) During the First 2 Days After Randomization
In the Usual Care Group, These Drugs were Administered as Primary Sedatives in 60%, 12%, and 20% of the Patients, Respectively
Bradycardia and Hypotension were More Common in the Dexmedetomidine Group
Recommendations (Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit; 2013) [MEDLINE]
Non-Benzodiazepine Sedatives (Propofol, Dexmedetomidine) are Recommended Over Benzodiazepine Sedatives (Lorazaepam, Midazolam) to Improve the Clinical Outcomes of Mechanically Ventilated Adult ICU Patients (Grade +2B Recommendation(
“Analgesia First” Sedation is Suggested in Mechanically Ventilated Adult ICU Patients (Grade +2B Recommendation)
Systematic Review of Sedatives in Traumatic Brain Injury (Crit Care MED, 2011) [MEDLINE]
No Evidence that Any Sedative is Superior to Another in Traumatic Brain Injury in Terms of Patient-Centered Outcomes, Intracranial Pressure, or Cerebral Perfusion Pressure
High Bolus Doses of Opiates Have Potentially Deleterious Effects on Intracranial Pressure and Cerebral Perfusion Pressure
Continuous Sedation Infusion
Potential Advantages
Continuous Sedation Infusion Provides a More Constant Level of Sedation than Intermittent Bolus Dosing and May Increase Patient Comfort
Potential Disadvantages
Continuous Sedation Infusion Increases Ventilator Days and ICU Length of Stay, as Compared to Intermittent Bolus Dosing
Continuous Sedation Infusion May Limit the Clinician’s Ability to Distinguish Changes in Mental Status (Perhaps Necessitating the Increased Use of Diagnostic Studies to Rule Out Neurologic Injury)
Depth of Sedation (and Daily “Sedation Vacation”)
Benefits of Minimization of Sedation/Daily “Sedation Vacation”
Decreases Intensive Care Unit Length of Stay [MEDLINE] [MEDLINE]
Decreases Rate of Various Intensive Care Unit-Related Complications [MEDLINE]
Decreases Total Amount of Midazolam Administered by 50%: but no demonstrated effect on the amount of propofol administered though
Decreases Total Duration of Mechanical Ventilation [MEDLINE] [MEDLINE]
Does Not Increase the Self-Extubation Rate [MEDLINE]
Clinical Efficacy
Studies Supporting the Performance of Paired Daily Sedation Vacation and Spontaneous Breathing Trials (SBT’s) (see 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
Study of Effect of Daily Sedation Vacation in Mechanically Ventilated Patients (NEJM, 2000) [MEDLINE]: daily sedation vacation decreased the duration of mechanical ventilation and the length of ICU stay
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 the duration of mechanical ventilation, weaning duration, and ICU length of stay
Other Studies
Study of Addition of Daily Sedation Vacation to a Sedation Protocol That Already Attempted to Minimize Sedation (JAMA, 2012) [MEDLINE]: daily sedation vacation resulted in an increased total sedative dose with no clinical benefit
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
Meta-Analysis of Use of Sedation Protocols in Mechanically-Ventilated Patients (Chest, 2017) [MEDLINE]: n = 6 trials
Protocolized Sedation Resulted in No Significant Difference in the Duration of Mechanical Ventilation (Mean Difference 1 Day Shorter; 95% CI: 2.14 to 0.14)
Protocolized Sedation Resulted in a Shorter ICU Length of Stay (Mean Difference 1.78 Days Shorter; 95% CI: –3.41 to –0.14)
Protocolized Sedation Resulted in No Difference in the Short-Term Mortality Rate (RR, 0.93; 95% CI: 0.77- 1.11; P=42
Danish NONSEDA Trial of Non-Sedation vs Light Sedation with Daily Sedation Vacation in Mechanically-Ventilated ICU Patients (NEJM, 2020) [MEDLINE]: n = 700 (intention-to-treat analysis)
In Mechanically-Ventilated ICU Patients, 90-Day Mortality was Similar Between the Non-Sedation Group and the Light Sedation with Daily Sedation Vacation Group
90-Day Mortality was 42.4% in the Non-Sedation Group and 37.0% in the Light Sedation with Daily Sedation Vacation Group (Difference, 5.4%; 95% Confidence Interval: −2.2 to 12.2; p=0.65)
The Number of ICU-Free Days and Ventilator-Free Days Did Not Differ Significantly Between the Groups
The Patients in the Non-Sedation Group had a Median of 27 Days Free from Coma or Delirium, and Those in the Light Sedation with Daily Sedation Vacation Group Had a Median of 26 Days Free from Coma or Delirium
A Major Thromboembolic Event Occurred in 1 Patient (0.3%) in the Non-Sedation Group and in 10 patients (2.8%) in the Light Sedation with Daily Sedation Vacation Group (Difference −2.5%; 95% CI, −4.8 to −0.7 [Unadjusted for Multiple Comparisons])
Recommendations (“Choosing Wisely” Campaign; Am J Resp Crit Care Med, 2014) [MEDLINE] and Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit; 2013) [MEDLINE]
“Choosing Wisely” Campaign Recommends Not Sedating Ventilated Patients Without a Specific Indication and Recommends Employing a Daily Sedation Vacation
Sedative Medications Should Be Titrated to Maintain a Light, Rather Than Deep, Level of Sedation, in Adult ICU Patients, Unless Clinically Contraindicated (Grade +1B Recommendation)
Maintaining a Light Level of Sedation in Adult ICU Patients is Associated with Improved Clinical Outcome (Shorter Duration of Mechanical Ventilation and Shorter ICU Length of Stay) (Grade B Recommendation)
Maintaining a Light Level of Sedation Increases the Physiologic Stress Response, But is Not Associated with an Increased Incidence of Myocardial Ischemia (Grade B Recommendation)
The Association Between Depth of Sedation and Psychological Stress in Adult ICU Patients Remains Unclear (Grade C Recommendation)
Daily “Sedation Vacation” Should Be Used Routinely in Mechanically Ventilated Adult ICU Patients (Grade +1B Recommendation)
An Interdisciplinary ICU Team Should Be Employed (with Provider Education, Protocols/Order Sets, and Quality ICU Rounds Checklists to Facilitate the Use of Pain, Agitation, and Delirium Management Guidelines/Protocols in Adult ICU’s (Grade +1B Recommendation)
Recommendations (American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline for Liberation from Mechanical Ventilation in Critically Ill Adults) (Chest, 2017) [MEDLINE]
For Acutely Hospitalized Patients Ventilated for >24 hrs, Protocols Attempting to Minimize Sedation are Recommended (Conditional Recommendation, Low Quality of Evidence)
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 [MEDLINE]
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 [MEDLINE]
Sedation, where are we now? Intensive Care Med 1999; 25:137-139 [MEDLINE]
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 [MEDLINE]
Short-term lorazepam infusion and concern for propylene glycol toxicity. Pharmacotherapy 2001; 21:1140 [MEDLINE]
Severe hyperosmolar metabolic acidosis due to a large dose of intravenous lorazepam. N Engl J Med 2002; 346:1253 [MEDLINE]
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 [MEDLINE]
Adverse events associated with sedatives, analgesics, and other drugs that provide patient comfort in the intensive care unit. Pharmacotherapy. 2005 May;25(5 Pt 2):8S-18S [MEDLINE]
Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006;104(1):21-26 [MEDLINE]
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]
Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit Care 2009;13:R75 [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]
Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012;308:1985-92 [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]
Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013 Sep;41(9 Suppl 1):S30-8. doi: 10.1097/CCM.0b013e3182a16898 [MEDLINE]
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]
Sedation and delirium in the intensive care unit. N Engl J Med. 2014;370:444–454 [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]
An official American Thoracic Society/American Association of Critical-Care Nurses/American College of Chest Physicians/Society of Critical Care Medicine policy statement: the Choosing Wisely® Top 5 list in Critical Care Medicine. Am J Respir Crit Care Med. 2014 Oct 1;190(7):818-26. doi: 10.1164/rccm.201407-1317ST [MEDLINE]
Predictors of physical restraint use in Canadian intensive care units. Crit Care. 2014;18(2):R46. doi: 10.1186/cc13789 [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]
Efficacy and safety of sedation with dexmedetomidine in critical care patients: a meta-analysis of randomized controlled trials. Anaesth Crit Care Pain Med. 2016 Feb;35(1):7-15. doi: 10.1016/j.accpm.2015.06.012. Epub 2015 Dec 11 [MEDLINE]
Liberation From Mechanical Ventilation in Critically Ill Adults: Executive Summary of an Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline. Chest. 2017 Jan;151(1):160-165. doi: 10.1016/j.chest.2016.10.037 [MEDLINE]
An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Chest. 2017 Jan;151(1):166-180. doi: 10.1016/j.chest.2016.10.036 [MEDLINE]
SPICE III Trial. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710 [MEDLINE]
Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients. N Engl J Med. 2020 Mar 19;382(12):1103-1111. doi: 10.1056/NEJMoa1906759 [MEDLINE]
Comparative Clinical Efficacy Studies of Induction Medications for Endotracheal Intubation
Pharmacological properties of ketamine. Drug Alcohol Rev. 1996 Jun;15(2):145-55 [MEDLINE]
KETASED Trial. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009 Jul 25;374(9686):293-300. doi: 10.1016/S0140-6736(09)60949-1 [MEDLINE]
Effects of etomidate on complications related to intubation and on mortality in septic shock patients treated with hydrocortisone: a propensity score analysis. Crit Care. 2012 Nov 21;16(6):R224. doi: 10.1186/cc11871 [MEDLINE]
Systematic assessment of dexmedetomidine as an anesthetic agent: a meta-analysis of randomized controlled trials. Arch Med Sci. 2014 Feb 24;10(1):19-24. doi: 10.5114/aoms.2014.40730 [MEDLINE]
Safety of Propofol as an Induction Agent for Urgent Endotracheal Intubation in the Medical Intensive Care Unit. J Intensive Care Med. 2015 Dec;30(8):499-504. doi: 10.1177/0885066614523100 [MEDLINE]
Use of propofol as an induction agent in the acutely injured patient. Eur J Trauma Emerg Surg. 2015 Aug;41(4):405-11. doi: 10.1007/s00068-014-0479-3 [MEDLINE]
Single-dose etomidate does not increase mortality in patients with sepsis: a systematic review and meta-analysis of randomized controlled trials and observational studies. Chest. 2015 Feb;147(2):335-346. doi: 10.1378/chest.14-1012 [MEDLINE]
Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients. Cochrane Database Syst Rev. 2015 Jan 8;1:CD010225. doi: 10.1002/14651858.CD010225.pub2 [MEDLINE]
Safety of Propofol as an Induction Agent for Urgent Endotracheal Intubation in the Medical Intensive Care Unit. J Intensive Care Med. 2015 Dec;30(8):499-504. doi: 10.1177/0885066614523100 [MEDLINE]
Ketamine and propofol combination (“ketofol”) for endotracheal intubations in critically ill patients: a case series. Am J Case Rep. 2015 Feb 13;16:81-6. doi: 10.12659/AJCR.892424 [MEDLINE]
Comparison of Etomidate and Ketamine for Induction During Rapid Sequence Intubation of Adult Trauma Patients. Ann Emerg Med. 2017 Jan;69(1):24-33.e2. doi: 10.1016/j.annemergmed.2016.08.009 [MEDLINE]
Ketamine/propofol admixture vs etomidate for intubation in the critically ill: KEEP PACE Randomized clinical trial. J Trauma Acute Care Surg. 2019 Oct;87(4):883-891. doi: 10.1097/TA.0000000000002448 [MEDLINE]
Sedation in Specific Clinical Settings
Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med. 2011;39:2743–2751 [MEDLINE]
Sedation in traumatic brain injury. Emerg Med Int. 2012; vol 2012; article ID 637171, pp 1–11 [MEDLINE]
Editor’s Choice- Sedation in the coronary intensive care unit: An adapted algorithm for critically ill cardiovascular patient. Eur Heart J Acute Cardiovasc Care. 2019 Mar;8(2):167-175. doi: 10.1177/2048872617753797 [MEDLINE]
