Sedation in ICU

OVERVIEW

• Sedation is the depression of a patient’s awareness to the environment and reduction of his or her responsiveness to external stimulation
• Sedative agents also have varying degrees of associated effects, which may be dose-dependent, such as:
  • Anxiolysis – Relief of apprehension or agitation with minimal alteration of sensorium
  • Amnesia –  memory loss for a period of time
  • Analgesia – relief of pain without an altered sensorium
  • Anaesthesia – loss of sensation
• Sedation is commonly used in ICU and sedation protocols are in widespread use and are considered best practice

DEPTH OF SEDATION

Depth of sedation is a continuum, that can be subjectively classified as:

• Minimal sedation — anxiolysis only
• Moderate sedation  — responsive to verbal or tactile stimuli (verbal or tactile); airway reflexes, spontaneous ventilation, and cardiovascular function are maintained.
• Deep sedation — responsive purposefully to repeated or painful stimuli; airway reflexes or spontaneous ventilation may not be maintained, but cardiovascular function is preserved.
• General anesthesia — a state of unconsciousness and profound unresponsiveness such that the autonomic nervous system is unable to respond to surgical or procedural stimuli.
• Dissociation — a distinct type of moderate sedation characteristic of phencyclidines such as ketamine that cause a disconnection between the thalamoneocortical system and the limbic systems, preventing higher centers from receiving sensory stimuli. Airway reflexes, spontaneous ventilation, and cardiovascular function are all maintained.

Monitoring of depth of sedation can be achieved by clinical assessment or physiological monitoring (See below).

USES

• allows patients to tolerate painful/distressing procedures (e.g. endotracheal intubation, invasive lines)
• optimise mechanical ventilation (e.g. tolerate permissive hypercapnea)
• used to decrease O2 consumption (e.g. sepsis)
• decrease ICP in neurosurgical patients
• facilitate cooling (e.g. therapeutic hypothermia)
• control agitation

IDEAL SEDATION AGENT

The ideal sedation agent does not exist. Features of the hypothetical ideal sedation agent are:

• Pharmaceutics
  • Ease of administration
  • Does not promote growth of pathogens
  • Easily prepared and long shelf life
• Pharmacodynamics
  • Predictable dose-dependent effects with minimal individual variation
  • Provides appropriate sedation, anxiolysis, amnesia and analgesia
  • No tolerance and withdrawal symptoms
  • Provides facilitation of ventilator synchrony and the performance of various procedures and nursing interventions
• Pharmacokinetics
  • Rapid onset of action
  • Easily titratable level of adequate sedation
  • Short-acting, allowing patient assessment, rapid recovery following discontinuation, easy weaning from mechanical ventilation, and early extubation
  • Minimal metabolism; not dependent on normal hepatic, renal, or pulmonary function
  • No active or toxic metabolites
  • Safe for all ages with no age-related changes in pharmacokinetics
  • Lack of accumulation with prolonged administration
• Interactions
  • No or minimal interactions with other drugs
• No or few adverse effects
  • No anaphylaxis or allergic reaction
  • No nausea, vomiting, or phlebitis
  • Minimal respiratory depression
  • Minimal effect on cardiovascular function
  • No pain on injection
  • No suppression of cortisol production by the adrenal cortex
• Other
  • Cost effective
  • Lack of abuse potential
  • Widely available

COMMONLY USED AGENTS

• propofol
• benzodiazepines, e.g. midazolam
• opioids, e.g. morphine, fentanyl
• alpha 2 agonists, e.g. dexmedetomidine, clonidine
• ketamine
• thiopentone
• tranquilisers, e.g. haloperidol

SIDE EFFECTS

• hypotension
• respiratory depression
• arrhythmias
• drug specific effects
• sleep disturbance
• withdrawal
• delirium

MONITORING

Subjective clinical assessment

• Richmond Agitation-Sedation Score (RASS) is the most-validated and most widely-used tool to assess depth of sedation (the Sedation-Agitation Scale (SAS) is a reasonable alternative)
• Views sedation and agitation as a continuum
• Not useful in patients receiving neuromuscular blocking agents
• Titrate almost all patients to a RASS score of -2 or higher (no more than light sedation); very ill or agitated patients (e.g., severe ARDS, raised ICP) may “rarely” require RASS -3 or -4

+4 Combative
+3 Very agitated
+2 Agitated
+1 Restless
0 Alert and calm
-1 Drowsy
-2 Light sedation
-3 Moderate sedation
-4 Deep sedation
-5 Unrousable

Procedure for RASS Assessment

1. Observe patient
   a. Patient is alert, restless, agitated or combative (score 0 to +4)
2. If not alert, state patient’s name and say to open eyes and look at speaker
   b. Patient awakens with sustained eye opening and eye contact (score –1)
   c. Patient awakens with eye opening and eye contact, but not sustained(score –2)
   d. Patient has any movement in response to voice but no eye contact (score –3)
3. When no response to verbal stimulation, physically stimulate patient by shaking shoulder and/or rubbing sternum
   e. Patient has any movement to physical stimulation (score –4)
   f. Patient has no response to any stimulation (score –5)

Objective physiological assessment

• objective measures of brain function (e.g., AEPs, BIS, NI, PSI, or SE) are poor substitutes for clinical assessment
• can be used as an adjunct in ICU patients who are receiving neuromuscular blocking agents, as subjective sedation assessments may be unobtainable
• EEG monitoring be used to:
  — monitor nonconvulsive seizure activity in adult ICU patients with either known or suspected seizures
  — titrate electrosuppressive medication to achieve burst suppression in adult ICU patients with elevated ICP

AN APPROACH TO SEDATION IN ICU

• Sedative medications should be titrated to maintain a light rather than a deep level of sedation in adult ICU patients, unless contraindicated
• keep patients comfortable and safe using the minimum possible amount of sedation
• use protocolised care with sedation score monitoring
• propofol is widely used as it usually allows rapid, predictable desedation
• daily sedation interruptions may not be necessary in ICUs with protocolised sedation
• review infusion rates at least daily, and after any procedures
• treat pain with boluses of analgesics (e.g. IV morphine or fentanyl), only make minor increases in basal infusion rates
• avoid prolonged deep coma whenever possible
• use caution in renal and liver failure
• use spontaneous breathing, unless contra-indicated
• dexmedetomidine is increasingly prefered in delirious patients requiring ongoing sedation

EVIDENCE

Summarised from Jacobi et al (2002) clinical practice guidelines:

• Maintaining light levels of sedation in adult ICU patients is associated with improved clinical outcomes
  — shorter duration of mechanical ventilation
  — shorter ICU length of stay
• Maintaining light levels of sedation increases the physiologic stress response, but is not associated with an increased incidence of myocardial ischemia
• The association between depth of sedation and psychological stress in lightly sedated patients is unclear
• The Richmond Agitation-Sedation Scale (RASS) and Sedation-Agitation Scale (SAS) are the most valid and reliable sedation assessment tools for measuring quality and depth of sedation in adult ICU patients
• nonbenzodiazepine sedatives (either propofol or dexmedetomidine) may be preferred over sedation with benzodiazepines (either midazolam or lorazepam) to improve clinical outcomes in mechanically ventilated adult ICU patients

References and Links

Journal articles: Trials

• Augustes R, Ho KM. Meta-analysis of randomised controlled trials on daily sedation interruption for critically ill adult patients. Anaesth Intensive Care. 2011 May;39(3):401-9. PubMed PMID: 21675059.
• Girard TD, et al. 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. PMID: 18191684.
• Jacobi J, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002 Jan;30(1):119-41. Erratum in: Crit Care Med 2002 Mar;30(3):726. PMID: 11902253.
• Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7. PMID: 10816184.
• Mehta S, et al; SLEAP Investigators; Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012 Nov 21;308(19):1985-92. Erratum in: JAMA. 2013 Jan 16;309(3):237. PMID: 23180503.
• Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010 Feb 6;375(9713):475-80. PMID: 20116842.

Journal articles: Reviews

• Hughes CG, McGrane S, Pandharipande PP. Sedation in the intensive care setting. Clin Pharmacol. 2012;4:53-63. PMC3508653.
• Weinhouse GL, Watson PL. Sedation and sleep disturbances in the ICU. Anesthesiol Clin. 2011 Dec;29(4):675-85. PMID: 22078916.

FOAM and web resources

• EMCrit Podcast 21 – A Bad Sedation Package Leaves your Patient Trapped in a Nightmare (2011)
• EMCrit – Podcast 115 – A New Paradigm for Post-Intubation Pain, Agitation, and Delirium (2013)
• PulmCCM.org — Sedation vacations don’t improve outcomes in large trial (RCT, JAMA)
• PulmCCM.org — Pain control and sedation in mechanically ventilated patients (Review, AJRCCM)
• ScanCrit — Sedated insomnia in the ICU
• ScanCrit — Gas the ICU