Patients who are in an intensive care unit (ICU) 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 of Agitation and Confusion
In a patient who is critically ill, 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.
Some Causes of Agitation or Confusion in Critical Care Patients
Mechanism | Examples |
|---|---|
Underlying disorder | Head injury Toxin ingestion Electrolyte abnormalities (eg, hypercalcemia, hypocalcemia, hypomagnesemia, hypernatremia, hyponatremia, hypophosphatemia) Pain and discomfort (eg, caused by injuries, surgical procedures, endotracheal intubation, IVs, blood drawing, or nasogastric tube) |
Complications | Hypotension Organ failure (eg, hepatic encephalopathy) |
Medications or substances | Sedatives and other drugs active in the central nervous system, particularly opioids, benzodiazepines, H2 blockers, and antihistamines Withdrawal from alcohol, illicit 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 of Agitation and Confusion
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. Medication 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, drug withdrawal, 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).
Continuously assessing the degree of agitation and the need for sedation are key to preventing increased morbidity. The 2 most commonly used sedation scales are the Richmond Agitation-Sedation Scale (RASS) and the Riker Sedation-Agitation Scale (SAS). The Ramsay Sedation Scale is also sometimes used. 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.
The Confusion Assessment Method (see table Confusion Assessment Method for Diagnosing Delirium) can be used to screen for delirium as a cause of agitation.
Richmond Agitation-Sedation Scale
Score | Term | Description |
|---|---|---|
+4 | Combative | Overly combative or violent; immediate danger to staff |
+3 | Very agitated | Pulls on or removes tube(s) or catheter(s) or has aggressive behavior toward staff |
+2 | Agitated | Frequent nonpurposeful movement or patient-ventilator dyssynchrony |
+1 | Restless | Anxious or apprehensive but movements not aggressive or vigorous |
0 | Alert and calm | — |
-1 | Drowsy | Not fully alert, but has sustained (more than 10 seconds) awakening, with eye contact, to voice |
-2 | Light sedation | Briefly (less than 10 seconds) awakens with eye contact to voice |
-3 | Moderate sedation | Any movement (but no eye contact) to voice |
-4 | Deep sedation | No response to voice, but any movement to physical stimulation |
-5 | Unarousable | No response to voice or physical stimulation |
Adapted from Sessler CN, Gosnell MS, Grap MJ, et al: The Richmond Agitation-Sedation Scale: Validity and reliability in adult intensive care unit patients. American Journal of Respiratory and Critical Care Medicine 166(10)1338–1344, 2002. doi: 10.1164/rccm.2107138 | ||
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 |
Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med. 1999;27(7):1325-1329. doi:10.1097/00003246-199907000-00022 | ||
The Ramsay Sedation Scale
Clinical Score | Patient Characteristics |
|---|---|
1 | Awake; agitated or restless or both |
2 | Awake; cooperative, oriented, and tranquil |
3 | Awake but responds to commands only |
4 | Asleep; brisk response to light glabellar tap or loud auditory stimulus |
5 | Asleep; sluggish response to light glabellar tap or loud auditory stimulus |
6 | Asleep; no response to glabellar tap or loud auditory stimulus |
Adapted from Ramsay MA, Savage TM, Simpson B, et al: Controlled sedation with alphaxalone-alphadolone. British Medical Journal 2(5920):656–659, 1974. doi: 10.1136/bmj.2.5920.656 | |
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?"
|
* 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. | |
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113(12):941-948. doi:10.7326/0003-4819-113-12-941 | |
Testing
Identified abnormalities (eg, hypoxia, hypotension, fever) should be clarified further with appropriate testing. Head CT need not routinely be performed unless focal neurologic findings are present or no other etiology is found. A bispectral index (BIS) monitor (specialized EEG monitor) placed on the head to capture cerebral cortex electrical activity may be helpful in determining the level of sedation or agitation of patients under neuromuscular blockade.
Treatment of Agitation and Confusion
Underlying conditions (eg, hypoxia, shock, sepsis, progression of traumatic brain injury) 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.
Medication treatment should treat the cause of symptoms. For example, pain is treated with analgesics; anxiety and insomnia are treated with sedatives; and psychosis and delirium are treated with small doses of an antipsychotic medication. Intubation may be needed when sedative and analgesic requirements are high enough to jeopardize the airway or respiratory drive. Many medications are available; generally, short-acting medications 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 medications. 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 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 medications. 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 offentanyl; individual requirements are highly variable.
Sedation
Despite analgesia, many critically ill patients who are intubated remain sufficiently agitated so as to also require sedation. A sedative can also provide patient comfort while permitting a lower dose of analgesic.
For short-term sedation, propofol (eg, 5 to 50 mcg/kg per minute in young, healthy patients), a sedative-hypnotic medication, may be used. Long-term use (≥ 48 hours) of high-dose For short-term sedation, propofol (eg, 5 to 50 mcg/kg per minute in young, healthy patients), a sedative-hypnotic medication, may be used. Long-term use (≥ 48 hours) of high-dosepropofol increases the risk of propofol infusion syndrome (PRIS), characterized by metabolic acidosis, rhabdomyolysis, hyperlipidemia, acute kidney injury, heart failure, and pancreatitis; it is often fatal (1, 2). Because elevated triglyceride levels (eg, > 400 mg/dL [ 4.52 mmol/L]) may herald PRIS (3), triglyceride levels must be measured after 2 to 3 days of high-dose propofol use.
Dexmedetomidine has anxiolytic, sedative, and some analgesic properties and does not affect respiratory drive. Dexmedetomidine has anxiolytic, sedative, and some analgesic properties and does not affect respiratory drive.Dexmedetomidine is commonly used for patients requiring mechanical ventilation. The character and depth of sedation caused by dexmedetomidine may permit patients receiving mechanical ventilation 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 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.
Benzodiazepines (eg, lorazepam, midazolam) may be used in some circumstances (eg,acute seizures/status epilepticus, alcohol withdrawal). 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 medications pose risks of respiratory depression, hypotension, delirium, and prolonged physiologic effects even after discontinuation in some patients. Long-acting benzodiazepines such as diazepam, flurazepam, and chlordiazepoxide should be avoided because these medications may delay extubation and prolong ICU stays when compared other medications (eg, propofol) () may be used in some circumstances (eg,acute seizures/status epilepticus, alcohol withdrawal). 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 medications pose risks of respiratory depression, hypotension, delirium, and prolonged physiologic effects even after discontinuation in some patients. Long-acting benzodiazepines such as diazepam, flurazepam, and chlordiazepoxide should be avoided because these medications may delay extubation and prolong ICU stays when compared other medications (eg, propofol) (4). Antipsychotics with less anticholinergic effect, such as haloperidol 1 to 3 mg IV, may work best when combined with benzodiazepines.). Antipsychotics with less anticholinergic effect, such as haloperidol 1 to 3 mg IV, may work best when combined with benzodiazepines.
Neuromuscular blockade
For intubated patients, neuromuscular blockade (eg, vecuronium given as a continuous infusion) is For intubated patients, neuromuscular blockade (eg, vecuronium given as a continuous infusion) isnot a substitute for adequate 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 medications (including dexmedetomidine) are used, neuromuscular blockade is rarely required. a substitute for adequate 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 medications (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 glucocorticoids are concomitantly given.
Treatment references
1. Li WK, Chen XJC, Altshuler D, et al. The incidence of propofol infusion syndrome in critically-ill patients. J Crit Care. 2022;71:154098. doi:10.1016/j.jcrc.2022.154098
2. Smith HAB, Besunder JB, Betters KA, et al. 2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility. Pediatr Crit Care Med. 2022;23(2):e74-e110. doi:10.1097/PCC.0000000000002873
3. Diaz JH, Prabhakar A, Urman RD, et al. Propofol infusion syndrome: A retrospective analysis at a level 1 trauma center. Crit Care Res Pract. 2014;2014:346968. doi: 10.1155/2014/346968
4. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. doi:10.1097/CCM.0000000000003299
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 such as propofol, dexmedetomidine, ketamine, or lorazepam.Treat the cause (including giving analgesics for pain and optimizing the environment to minimize confusion) and manage any remaining agitation with a sedative such as propofol, dexmedetomidine, ketamine, or lorazepam.
Neuromuscular blockade merely masks pain and agitation; paralyzed patients may be suffering significantly.
Drugs Mentioned In This Article
