Sedation in Critically-Ill Patients

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

Introduction

Sedation, ICU

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; intravenous lines; 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; 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 refers to the reduction of anxiety, stress, irritability, or excitement via administration of a sedative drugs. Sedative's actions involves increasing the neurotransmitter gamma-aminobutyric acid (GABA) within brain. GABAs role is to slow down the transmission of the brains signals.

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

In need of deep 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, prevention of awareness in patients treated with neuromuscular blocking agents.

Commonly Used Sedative Agents

Analgesics and sedatives are used to allow patients to tolerate nursing actions and tracheal intubation and to aid mechanical ventilation. Sedative therapy can be managed using a variety of drug agents, including:

• Benzodiazepines (midazolam, lorazepam, diazepam), midazolam and lorazepam tend to be used for medium- and long-term use.
• Ketamine
• Propofol (often favored for short-term sedation and ventilator weaning).
• Isoflurane
• Chloral derivatives
• Barbiturates (have largely been replaced by alternatives)
• Centrally acting alpha-2 agonists (decrease sympathetic nervous system activity) eg clonidine, dexmedetomidine. Dexmedetomidine is useful for minimizing the risk of delirium and maintaining patient interactivity under light sedation. 
• Clomethizole,
• Neuroleptics (droperidol, haloperidol)

Analgosedation agents: may also used for sedative therapy. 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. These agents are pain relieving drugs with a sedative effect and include:

• Fentanyl

• Remifentanil
• Morphine

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.

Benzodiazepines are associated with an increased risk of delirium, increased time on mechanical ventilation, and prolonged ICU stay.

Assessment and Monitoring

Man in coma, ICU

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)

Protocols

Sediation

Sedation protocols should be standard in ICU, and followed by staff. These protocols need to be regularly updated.

PADIS guidelines (developed to help ensure consistent, evidence-based care of critical care patients utilising the most up-to-date, relevant knowledge available) recommend the following:

• Depth of sedation be monitored regularly with a valid and reliable subjective scale.

• If a subjective scale cannot be used, (eg 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)

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

Sedation Vacations

Pharmacological sedation in the ICU is evolving. Traditionally, patients who were mechanically ventilated in the ICU were kept deeply sedated aiming for continuous depressant infusions to help with ventilation and decrease discomfort that may occur during critical illness. Data from early 2000's suggested that continuous infusions of sedative medications made for worse clinical outcomes.

1. Sedation vacations involves ceasing the sedative infusions, allowing the patient to wake. The infusion is restarted only when the patient is fully awake and obeying commands or until they became uncomfortable/agitated and require restarting sedation (ideally performed on a daily basis). This strategy: reduces the duration of mechanical ventilation; decreases length of stay in ICU.
2. Sedation vacations are a balancing act of carefully titrating the sedative dose to provide agitation-free, comfortable sedation at the lowest dosage viable

Physical Therapy Implications

Physiotherapist reading charts

To endure patient a multidisciplinary approach (in addition to pharmacotherapy) is needed. Physiotherapy plays an important role as prolonged immobility may be painful and this can be reduced by daily assessment and treatment.

When treating those sedated in ICU knowledge of sedative agents, depths of sedation, sedation protocols, and tools for assessment are critical. They help with gauging patient readiness for skilled therapy intervention and early mobility in ICU, and communicating with other professionals in the ICU.

Physical therapists also 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