Sedation in Critically-Ill Patients

Original Editor - Karen Wilson Top Contributors - Karen Wilson

Introduction[edit | edit source]

Critical care is full of potential stressors.  A review by Walder et al.[1] found that up to 71% of critically-ill patients experience agitation, confusion, and anxiety during their ICU stay. Common stressors include pain, sleeplessness, mechanical ventilation, tubes in the nose and mouth, genitourinary catheters, noise, hallucinations, discomfort due to medical procedures, thoughts of death, and uncertainty.[1][2] Left untreated, inadequate sedation can lead to unplanned extubation, pulmonary and cardiac complications, increased time on mechanical ventilation, and prolonged ICU stay.[1][3] As a result, use of sedative agents is common to enhance patient comfort, facilitate therapeutic procedures, and avoid preventable complications.

Definitions[edit | edit source]

Sedation is defined as the act of calming.[1] In critical care, this typically refers to the administration of centrally acting drugs, but may also include non-pharmacological tools such as music, information, and reassurance. Sedative agents are associated with the following effects:[4]

  • Anxiolysis- relief of anxiety, stress, or agitation
  • Analgesia- relief of pain
  • Anesthesia- loss of sensation
  • Amnesia- loss of memory for a block of time  

Depth of Sedation[edit | edit source]

Dosing can alter the effect of sedative agents.[4] At minimal levels, sedation may only have an anxiolytic effect. At deeper levels of sedation, responsiveness, airway reflexes, and spontaneous ventilation are impacted. Table 1 summarizes the different levels of sedation seen in critical care.[4]

Table 1. Depth of Sedation

Depth Description
Minimal or light sedation Relief of anxiety or agitation (anxiolysis) only
Moderate sedation Responsive to tactile or verbal stimuli (verbal or tactile); cardiovascular function, spontaneous ventilation, and airway reflexes are maintained.
Deep sedation Purposefully responsive to painful or repeated stimuli; spontaneous ventilation or airway reflexes may not be maintained, however cardiovascular function is preserved.

Indications[edit | edit source]

There are numerous indications for sedation. In most cases, a minimal sedation protocol is used to help patients remain “calm, lucid, pain-free, interactive, and cooperative with their care.”[5] Deep sedation is only warranted under select circumstances. Table 2 contains a non-exhaustive list of indications for minimal and deep sedation.[2][5][6]  

Table 2. Indications by Sedation Protocol

Sedation Protocol Indications
Minimal sedation
  • Minimize stress response in critically ill patients
  • Decrease anxiety
  • Increase tolerance for ventilator support
  • Facilitate nurse/doctor interventions such as aspiration and dressing changes
  • Improve patient comfort
Deep sedation
  • Treatment of specific medical conditions including:
    • intracranial hypertension,
    • severe respiratory failure,
    • refractory status epilepticus,
    • and prevention of awareness in patients treated with neuromuscular blocking agents.

Commonly Used Sedative Agents[edit | edit source]

Sedative therapy can be managed using a variety of drug agents:[1][5]

  • Benzodiazepines (midazolam, lorazepam, diazepam)
  • Ketamine
  • Propofol
  • Isoflurane
  • Chloral derivatives
  • Barbiturates (have largely been replaced by alternatives)
  • Centrally acting alpha-2 agonists (clonidine, dexmedetomidine)
  • Clomethizole,
  • Neuroleptics (droperidol, haloperidol)

Among the most common are propofol, dexmedetomidine, midazolam, and lorazepam.[1] Propofol is often favored for short-term sedation and ventilator weaning, while midazolam and lorazepam tend to be used for medium- and long-term use.[1][5][6] Dexmedetomidine is useful for minimizing the risk of delirium and maintaining patient interactivity under light sedation.    

Analgosedation agents may be used for sedative therapy as well.[1][5][7] These agents are pain relieving drugs that also have a sedative effect:

  • Fentanyl
  • Remifentanil
  • Morphine

Early research suggests that analgosedation agents, particularly Remifentanil, may reduce sedative requirements, reduce ventilator time, and decrease ICU length of stay when used as first-line treatment for light sedation.[7]

Negative Side Effects[edit | edit source]

The negative side effects of pharmacological sedation vary by agent. The general side effects of sedatives include the following:[4][7]

  • Hypotension
  • Respiratory depression
  • Heart arrhythmias
  • Withdrawal
  • Delirium
  • Sleep disturbance
  • Toxicity

In particular, benzodiazepines are associated with an increased risk of delirium, increased time on mechanical ventilation, and prolonged ICU stay.[1]

The general side effects of analgosedation agents include:[6][7]

  • Delirium (namely, morphine)
  • Immunosuppression
  • Withdrawal
  • Decreased gastric motility
  • Hallucinations
  • Nausea and vomiting
  • Pruritus
  • Respiratory depression

Assessment and Monitoring[edit | edit source]

Regular assessment of sedation and agitation are important for ensuring adequate patient arousal. Consistent monitoring likely reduces over-sedation, the use of unnecessary imaging to assess patients’ neurological status, and negative patient outcomes.[1] Below are common scales used to measure sedation and agitation:

Clinical Guidelines[edit | edit source]

Pain, agitation, and delirium (PAD) are separate, but interlinked challenges for managing critically-ill patients.[5] Thus, clinical guidelines for sedation therapy are presented and best implemented in coordination with recommendations for reducing pain and delirium. More recently, immobility and sleep have been added to develop the Pain, Agitation, Delirium, Immobility, and Sleep (PADIS) guidelines.

With respect to agitation and sedation, the PADIS guidelines recommend the following:[8]

  • Source: Pixabay, License: Creative Commons
    Depth of sedation should be monitored regularly with a valid and reliable subjective scale.
  • When a subjective scale cannot be used, as in deep sedation or neuromuscular blockade, Bispectral Index (BIS) monitoring is best suited for guiding titration.
  • In critically ill, mechanically ventilated patients, propofol or dexmedetomidine should be used over benzodiazepines to minimize delirium.
  • When possible, sedation should be minimized using daily awakening trials or continuous monitoring with light sedation targets.

These guidelines and ongoing research acknowledge two areas in need of further investigation:[6][7][8]

  1. Sedative choice in terms of analgosedation, and
  2. Sedative choice for certain patient subgroups (ex. patients who are hemodynamically unstable, have neurological injuries, extensive burns, and/or COVID-19 infection)

Despite the aforementioned limitations, Dale et al[9] found that a PAD protocol helped to increase agitation and delirium assessment, reduce the use of benzodiazepines, decrease delirium, decrease time on mechanical ventilation, and decrease ICU length of stay and hospitalization. Additional benefits may include reduced tracheostomy rate.[10]

Ongoing challenges include the adoption of up-to-date sedation guidelines by facilities.[11][12]

Physical Therapy Implications[edit | edit source]

Knowledge of sedative agents, depths of sedation, sedation protocols, and tools for assessment are critical for providing early mobility in the ICU. They help with gauging patient readiness for skilled therapy intervention, identifying patients’ unmet care needs, and communicating with other professionals in the ICU.

In addition, physical therapists may engage in non-pharmacological means of reducing patient anxiety and agitation to minimize the need for sedative agents. Strategies may include:[2]

  • Making explanations to patients before performing any interventions
  • Providing frequent orientation and reassurance
  • Using alternative means of communication for non-verbal patients (ex. writing, communication boards)
  • Trying to identify and eliminate causes of pain
  • Coordinating analgesic administration with therapy sessions
  • Repositioning for comfort
  • Frequently cleaning oral secretions
  • Regularly checking the location and fixation of lines and tubes

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Walder B, Tramèr MR. Analgesia and sedation in critically ill patients. Swiss medical weekly. 2004 Jun 12;134(23-24):333-46.
  2. 2.0 2.1 2.2 Topçu S, Ecevit Alpar Ş, Gülseven B, Kebapçı A. Patient experiences in intensive care units: a systematic review. Patient Experience Journal. 2017;4(3):115-27.
  3. Jaber S, Chanques G, Altairac C, Sebbane M, Vergne C, Perrigault PF, Eledjam JJ. A prospective study of agitation in a medical-surgical ICU: incidence, risk factors, and outcomes. Chest. 2005 Oct 1;128(4):2749-57. [abstract only]
  4. 4.0 4.1 4.2 4.3 Nickson, C. Sedation in the ICU. Last updated March 30, 2019. Accessed 8 August 2020 at
  5. 5.0 5.1 5.2 5.3 5.4 5.5 Reade MC, Finfer S. Sedation and delirium in the intensive care unit. New England Journal of Medicine. 2014 Jan 30;370(5):444-54.
  6. 6.0 6.1 6.2 6.3 Makii JM, Mirski MA, Lewin III JJ. Sedation and analgesia in critically ill neurologic patients. Journal of pharmacy practice. 2010 Oct;23(5):455-69.
  7. 7.0 7.1 7.2 7.3 7.4 Devabhakthuni S, Armahizer MJ, Dasta JF, Kane-Gill SL. Analgosedation: a paradigm shift in intensive care unit sedation practice. Annals of Pharmacotherapy. 2012 Apr;46(4):530-40.
  8. 8.0 8.1 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJ, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Critical care medicine. 2018 Sep 1;46(9):e825-73.
  9. Dale CR, Kannas DA, Fan VS, Daniel SL, Deem S, Yanez III ND, Hough CL, Dellit TH, Treggiari MM. Improved analgesia, sedation, and delirium protocol associated with decreased duration of delirium and mechanical ventilation. Annals of the American Thoracic Society. 2014 Mar;11(3):367-74.
  10. Society of Critical Care Medicine. PADIS guidelines teaching slides: sedation. Accessed 20 Aug 2020:
  11. Tallgren M, Pettilä V, Hynninen M. Quality assessment of sedation in intensive care. Acta anaesthesiologica scandinavica. 2006 Sep;50(8):942-6. (abstract only)
  12. Arroyo-Novoa CM, Figueroa-Ramos MI, Puntillo KA. Occurrence and practices for pain, agitation, and delirium in intensive care unit patients. Puerto Rico health sciences journal. 2019 Sep;38(3):156.