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Agitation, Confusion, and Neuromuscular Blockade in Critically Ill Patients

By

Cherisse Berry

, MD, New York University School of Medicine

Last full review/revision Nov 2020| Content last modified Nov 2020
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Topic Resources

Intensive care unit (ICU) patients are often agitated, confused, and uncomfortable. They can become delirious (ICU delirium). These symptoms are unpleasant for patients and often interfere with care and safety. At worst, they may be life threatening (eg, patients dislodge the endotracheal tube or IV lines).

Etiology

In a critically ill patient, agitation, confusion, or both can result from the original medical condition, from medical complications, or from treatment or the ICU environment (see table Some Causes of Agitation or Confusion in Critical Care Patients). It is important to remember that neuromuscular blockade merely masks pain and agitation, it does not prevent it; paralyzed patients may be suffering significantly.

Table
icon

Some Causes of Agitation or Confusion in Critical Care Patients

Mechanism

Examples

Underlying disorder

Head injury

Toxin ingestion

Pain and discomfort (eg, caused by injuries, surgical procedures, endotracheal intubation, IVs, blood drawing, or nasogastric tube)

Complications

Hypoxia (see Oxygen Desaturation)

Hypotension

Organ failure (eg, hepatic encephalopathy)

Drugs

Sedatives and other drugs active in the central nervous system, particularly opioids, benzodiazepines, H2 blockers, and antihistamines

Withdrawal from alcohol, drugs, or both

Intensive care unit (ICU) environment*

Sleep deprivation (eg, due to noise, bright lights, or round-the-clock medical interventions)

Fear of death

Anxiety about unpleasant medical procedures

* Particularly a problem for older adults

Evaluation

The chart should be reviewed and the patient examined before sedatives are ordered for “agitation.”

History

The presenting injury or illness is a prime causative suspect. Nursing notes and discussion with personnel may identify downward trends in blood pressure and urine output (suggesting hypoperfusion of the central nervous system [CNS]) and dysfunctional sleep patterns. Drug administration records are reviewed to identify inadequate or excessive analgesia and sedation.

Past medical history is reviewed for potential causes. Underlying liver disease suggests possible portosystemic encephalopathy (hepatic encephalopathy). Known substance dependency or abuse suggests a withdrawal syndrome.

Awake, coherent patients are asked what is troubling them and are questioned specifically about pain, dyspnea, and previously unreported substance dependency.

Physical examination

Oxygen saturation < 90% suggests a hypoxic etiology. Low blood pressure and urine output suggest CNS hypoperfusion. Fever and tachycardia suggest sepsis or delirium tremens. Neck stiffness suggests meningitis, although this finding may be difficult to demonstrate in an agitated patient. Focal findings on neurologic examination suggest stroke, hemorrhage, or increased intracranial pressure (ICP).

The degree of agitation can be quantified using a scale such as the Riker Sedation-Agitation Scale (see table Riker Sedation-Agitation Scale) or the Ramsay Sedation Scale, which grades patients on a scale from 1, the patient is anxious, to 6, the patient shows no response. The Confusion Assessment Method (see table Confusion Assessment Method for Diagnosing Delirium) can be used to screen for delirium as a cause of agitation. Use of such scales allows better consistency between observers and the identification of trends. Patients who are under neuromuscular blockade are difficult to evaluate because they may be highly agitated and uncomfortable despite appearing motionless. It is typically necessary to allow paralysis to wear off periodically (eg, daily) so that the patient can be assessed.

Table
icon

Riker Sedation-Agitation Scale

Score

Description

Explanation

7

Dangerous agitation

Tries to remove monitors and devices or climb out of bed; tosses and turns; lashes out at staff

6

Very agitated

Remains restless despite frequent verbal reassurance; bites endotracheal tube; requires restraint

5

Agitated

Anxious or restless; attempts to move; calms down with reassurance

4

Calm and cooperative

Calm; easy to arouse; able to follow instructions

3

Sedated

Difficult to awaken; responds to verbal prompts or gentle shaking but drifts off again

2

Very sedated

Incommunicative; responds to physical stimuli but not verbal instructions; may move spontaneously

1

Unarousable

Incommunicative; little or no response to painful stimuli

Table
icon

Confusion Assessment Method (CAM) for Diagnosing Delirium*

Feature

Assessment†

Required features

Acute onset and fluctuating course

Shown by positive responses to the following questions:

"Has the patient’s mental status changed abruptly from baseline?"

"Did the abnormal behavior fluctuate during the day (ie, tend to come and go or increase and decrease in severity)?"

Inattention

Shown by a positive response to the following question:

"Did the patient have difficulty focusing attention (eg, was easily distracted or had difficulty following what was being said)?"

One of the following features required

Disorganized thinking

Shown by a positive response to the following question:

"Was the patient's thinking disorganized or incoherent (eg, evidenced by rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject)?"

Altered level of consciousness

Shown by any answer other than "alert" to the following question:

"Overall, how would you rate this patient's level of consciousness?"

  • Normal = alert

  • Hyperalert = vigilant

  • Drowsy, easily aroused = lethargic

  • Difficult to arouse = stupor

  • Unarousable = coma

* The diagnosis of delirium requires the presence of the first 2 features plus one of the second 2 features.

† This information is usually obtained from a family member or nurse.

Testing

Identified abnormalities (eg, hypoxia, hypotension, fever) should be clarified further with appropriate testing. Head CT need not routinely be done unless focal neurologic findings are present or no other etiology is found. A bispectral index (BIS) monitor placed on the head to capture cerebral cortex electrical activity may be helpful in determining the level of sedation/agitation of patients under neuromuscular blockade.

Treatment

Underlying conditions (eg, hypoxia, shock, drugs) should be addressed. The environment should be optimized (eg, darkness, quiet, and minimal sleep interruption at night) as much as is compatible with medical care. Clocks, calendars, outside windows, and TV or radio programs also help connect the patient with the world, lessening confusion. Family presence and consistent nursing personnel may be calming.

Drug treatment is dictated by the most vexing symptoms. Pain is treated with analgesics; anxiety and insomnia are treated with sedatives; and psychosis and delirium are treated with small doses of an antipsychotic drug. Intubation may be needed when sedative and analgesic requirements are high enough to jeopardize the airway or respiratory drive. Many drugs are available; generally, short-acting drugs are preferred for patients who need frequent neurologic examination or who are being weaned to extubation.

Analgesia

Pain should be treated with appropriate doses of IV opioids; conscious patients with painful conditions (eg, fractures, surgical incisions) who are unable to communicate should be assumed to have pain and receive analgesics accordingly. Mechanical ventilation is somewhat uncomfortable, and patients generally should receive a combination of opioid and amnestic sedative drugs. Fentanyl is the opioid of choice for short-term treatment because of its potency, short duration of action, and minimal cardiovascular effects. A common regimen can be 30 to 100 mcg/hour of fentanyl; individual requirements are highly variable.

Sedation

Despite analgesia, many patients remain sufficiently agitated so as to require sedation. A sedative can also provide patient comfort at a lower dose of analgesic. Benzodiazepines (eg, lorazepam, midazolam) are most common. A common regimen for sedation is lorazepam 1 to 2 mg IV every 1 to 2 hours or a continuous infusion at 1 to 2 mg/hour if the patient is intubated. These drugs pose risks of respiratory depression, hypotension, delirium, and prolonged physiologic effects in some patients. Long-acting benzodiazepines such as diazepam, flurazepam, and chlordiazepoxide should be avoided in older adults. Antipsychotics with less anticholinergic effect, such as haloperidol 1 to 3 mg IV, may work best when combined with benzodiazepines.

For short-term sedation, propofol (eg, 5 to 50 mcg/kg per minute in young, healthy patients), a sedative-hypnotic drug, may be used. Long-term use of high-dose propofol increases the risk of propofol infusion syndrome (PRIS), characterized by metabolic acidosis, rhabdomyolysis, hyperlipidemia, acute kidney injury, heart failure, and is often fatal.

Dexmedetomidine has anxiolytic, sedative, and some analgesic properties and does not affect respiratory drive. The risk of delirium is lower than with benzodiazepines. Because of these lower rates, dexmedetomidine is an increasingly used alternative to benzodiazepines for patients requiring mechanical ventilation. The character and depth of sedation caused by dexmedetomidine may permit mechanically ventilated patients to interact or be easily awakened, yet remain comfortable. The most common adverse effects are hypotension and bradycardia. Typical dosing is 0.2 to 0.7 mcg/kg/hour, but some patients require doses up to 1.5 mcg/kg/hour. Dexmedetomidine is usually used only for brief periods (eg, < 48 hours).

Ketamine is a dissociative anesthetic that provides analgesia and sedation. Ketamine acts as a NMDA (N-methyl-D-aspartate) noncompetitive antagonist. Benefits of ketamine include maintenance of respiratory drive and minimal cardiovascular depression. Ketamine also has bronchodilator effects, which may be beneficial in patients with asthma. The most common adverse effects include laryngospasm and visual hallucinations. Typical dosing is 1 to 2 mg/kg IV, followed by 0.5 to 1 mg/kg IV as needed.

Neuromuscular blockade

For intubated patients, neuromuscular blockade is not a substitute for sedation; it only removes visible manifestations of the problem (agitation) without correcting it. However, neuromuscular blockade may be required during tests (eg, CT, MRI) or procedures (eg, central line placement) that require patients to be motionless or in patients who cannot be ventilated despite adequate analgesia and sedation. When sedative drugs (including dexmedetomidine) are used, neuromuscular blockade is rarely required.

Prolonged neuromuscular blockade should be avoided unless patients have severe lung injury and cannot do the work of breathing safely. Use for > 1 to 2 days may lead to prolonged weakness, particularly when corticosteroids are concomitantly given. Common regimens include vecuronium (continuous infusion as directed by stimulation).

Key Points

  • Agitation, confusion, or both can result from the original medical condition, from complications of the acute illness, from treatment, or from the ICU environment.

  • History and physical examination often suggest a cause and direct subsequent testing.

  • Treat the cause (including giving analgesics for pain and optimizing the environment to minimize confusion) and manage any remaining agitation with a sedative drug such as lorazepam, propofol, dexmedetomidine, or ketamine.

  • Neuromuscular blockade merely masks pain and agitation; paralyzed patients may be suffering significantly.

Drugs Mentioned In This Article

Drug Name Select Trade
LIBRIUM
PRECEDEX
HALDOL
No US brand name
ATIVAN
KETALAR
VALIUM
DIPRIVAN
ACTIQ, DURAGESIC, SUBLIMAZE
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