Sedation in Critically-Ill Patients

Original Editor - Karen Wilson Top Contributors - Lucinda hampton and Karen Wilson

Introduction

Critical care is full of potential stressors.  A review by Walder et al. 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. Left untreated, inadequate sedation can lead to unplanned extubation, pulmonary and cardiac complications, increased time on mechanical ventilation, and prolonged ICU stay. As a result, use of sedative agents is common to enhance patient comfort, facilitate therapeutic procedures, and avoid preventable complications.

Definitions

Sedation is defined as the act of calming. 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:

• 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

Dosing can alter the effect of sedative agents. 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.

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

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.” Deep sedation is only warranted under select circumstances. Table 2 contains a non-exhaustive list of indications for minimal and deep sedation.  

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

Sedative therapy can be managed using a variety of drug agents:

• 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. 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. 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. 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.

Negative Side Effects

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

• 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.

The general side effects of analgosedation agents include:

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

Assessment and Monitoring

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. Below are common scales used to measure sedation and agitation:

• Richmond Agitation-Sedation Scale (RASS)
• Riker Sedation-Agitation Scale (SAS)
• Ramsay Sedation Scale (RSS)

Clinical Guidelines

Pain, agitation, and delirium (PAD) are separate, but interlinked challenges for managing critically-ill patients. 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:

• 

  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:

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 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.

Ongoing challenges include the adoption of up-to-date sedation guidelines by facilities.

Physical Therapy Implications

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:

• 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