Sedation, Agitation, Delirium: Assessment and Management

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Chapter 10

Sedation, Agitation, Delirium

Assessment and Management

Mary E. Lough

One of the challenges facing clinicians is how to provide a therapeutic healing environment for patients in the alarm-filled, emergency-focused critical care unit. Many critical care patients demonstrate agitation and discomfort caused by painful procedures, invasive tubes, sleep deprivation, fear, anxiety, and physiologic stress. Clinical practice guidelines were developed by the Society of Critical Care Medicine (SCCM) to increase awareness of these issues in the critically ill. The initial guidelines were released in 2002 ¹ and substantially revised in 2013.²

Sedation

Sedation and Agitation Assessment Scales

The use of scoring systems to assess and record levels of sedation and agitation is now strongly recommended.1,2 Four frequently used scales are the Ramsay Scale,³ the Riker Sedation-Agitation Scale (SAS),⁴ the Motor Activity Assessment Scale (MAAS),⁵ and the Richmond Agitation-Sedation Scale (RASS)^6,7 (Table 10-1). The two scales that are recommended for assessment of agitation and sedation in the adult critically ill patient are the SAS and the RASS.² Because individuals do not metabolize sedative medications at the same rate, the use of a standardized scale will ensure that continuous infusions of sedatives such as propofol or dexmedetomidine are titrated to a specific goal. Collaboratively, the critical care team must determine which level of sedation is most appropriate for each individual patient.

TABLE 10-1

SEDATION SCALES

Pain Assessment Scales

The first step in assessing the agitated patient is to rule out any sensations of pain.1,2 Clinical assessment is more challenging when the patient is obtunded or has an artificial airway in place. If the patient can communicate, the verbal pain scale of 0 to 10 is very useful. If the patient is intubated and cannot vocalize, pain assessment becomes considerably more complex. The Behavioral Pain Scale (BPS) and the Critical-Care Pain Observation Scale (CPOT) are the most reliable behavioral pain scales for monitoring of pain in critically ill adults.² These pain scales are shown in Table 9-1 (BPS) and Table 9-2 (CPOT) in Chapter 9. Pre-emptive analgesia should be provided before painful procedures.² The next step is to determine the minimum level of sedation required^1,2 (Box 10-1). The SCCM guidelines recommend that all critically ill, intubated, mechanically ventilated patients have stated goals for analgesia and sedation.² Assessment, treatment and prevention strategies for the management of pain are listed in Figure 9-6 in Chapter 9.

Box 10-1

Levels of Sedation

Light Sedation (Minimal Sedation, Anxiolysis)

Medication-induced state during which patients respond normally to verbal commands. Although cognitive function and coordination may be impaired, ventilatory and cardiovascular functions are unaffected.

Moderate Sedation with Analgesia (Conscious Sedation, Procedural Sedation)

Medication-induced depression of consciousness during which patients respond purposefully to verbal commands, alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway, and spontaneous ventilation is adequate. Cardiovascular function is usually maintained.

Deep Sedation and Analgesia

Medication-induced depression of consciousness during which patients cannot be easily aroused but respond purposefully after repeated or painful stimulation. The ability to maintain ventilatory function independently is impaired. Patients require assistance in maintaining a patent airway, and spontaneous ventilation may be inadequate. Cardiovascular function is usually maintained.

General Anesthesia

Medication-induced loss of consciousness during which patients are not arousable, even by painful stimulation. The ability to maintain ventilatory function independently is impaired, and assistance to maintain a patent airway is required. Positive-pressure ventilation may be required because of depressed spontaneous ventilation or medication-induced depression of neuromuscular function. Cardiovascular function may be impaired.

Data from Joint Commission on Accreditation of Healthcare Organizations. Comprehensive Accreditation Manual for Hospitals. Oakbrook Terrace, IL: The Joint Commission; 2000; Jacobi J, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30:119.

Complications of Sedation

Oversedation is recognized as a state of unintended patient unresponsiveness in which the patient resides in a state of suspended animation resembling general anesthesia. Prolonged deep sedation is associated with significant complications of immobility, including pressure ulcers, thromboemboli, gastric ileus, nosocomial pneumonia, and delayed weaning from mechanical ventilation.

Pharmacologic Management of Sedation

Several categories of sedatives are available. If the patient is experiencing pain, analgesia must be administered in addition to any sedative agents. Sedative agents include the benzodiazepines, sedative-hypnotic agents such as propofol, and the central alpha agonist dexmedetomidine (Table 10-2).¹ Currently dexmedetomidine-based and propofol-based sedative regimens are recommended for routine sedation of mechanically ventilated adult patients.²

TABLE 10-2

PHARMACOLOGIC MANAGEMENT
Sedation

MEDICATION	DOSAGE	ACTION	SPECIAL CONSIDERATIONS
Benzodiazepines
*Diazepam*	Loading Dose IV: 5-10 mg slowly Maintenance Dose IV: 0.03-01 mg/kg every 0.5-6.0 hr PRN	Anxiolysis Sedation	Onset: 2-5 min after IV administration Side effects: hypotension, respiratory depression Half-life: long (20-120 hr); active metabolites also contribute to prolonged sedative effect Tolerance: physical tolerance develops with prolonged use, and higher doses of medication are required to achieve the same effect over time; slow wean required from diazepam after continuous prolonged use Phlebitis occurs with peripheral IV administration
*Lorazepam*	Loading Dose IV: 0.02-0.04 mg/kg (≤2 mg) slowly	Anxiolysis Amnesia Sedation	Onset: 15-20 min after IV administration Side effects: hypotension, respiratory depression, propylene glycol-related acidosis, nephrotoxicity Half-life: relatively long (8-15 hr)
	Intermittent maintenance IV every 2-6 hr: 0.02-0.6 mg/kg slowly Continuous IV maintenance infusion: 0.01-0.1 mg/kg/hr (≤10 mg/hr)		Tolerance: physical tolerance develops with use, and higher medication dosage is required to achieve the same effect over time; slow wean required from lorazepam after continuous prolonged use Solvent-related acidosis and kidney failure occur at high doses
*Midazolam*	Loading Dose IV: 0.01-0.05 mg/kg slowly over several minutes	Anxiolysis Amnesia Sedation	Onset: 2-5 min after IV administration Side effects: hypotension, respiratory depression Half-life: 3-11 hr; sedative effect is prolonged when midazolam infusion has continued for many days, due to presence of active sedative metabolites; sedative effect is also prolonged in kidney failure
	Continuous IV maintenance infusion: 0.02-0.1 mg/kg		Tolerance: physical tolerance develops with prolonged use, and higher medication dosages are required to achieve the same effect over time; slow wean required from midazolam after prolonged use
Sedative-Hypnotics
*Propofol*	Loading Dose IV: 5 mcg/kg/min over 5 min Continuous IV maintenance infusion: 5-50 mcg/kg/min	Anxiolysis Amnesia Sedation	Onset: very rapid onset (1-2 min) after IV administration Side effects: hypotension, respiratory depression (patient must be intubated and mechanically ventilated to eliminate this complication), pain at the injection site if administered via peripheral IV; pancreatitis; hyper triglyceridemia, propofol related infusion syndrome (PRIS), allergic reactions Half-life: 1-2 min when used as a short-term agent Half-life: 3-68 hours with prolonged continuous IV infusion; effective short-term anesthetic agent, useful for rapid “wake-up” of patients for assessment; if continuous infusion is used for many days, emergence from sedation can take hours or days; sedative effect depends on dose administered, depth of sedation, and length of time sedated Change IV infusion tubing every 12 hr Requires a dedicated IV catheter and tubing (do not mix with other medications) Monitor serum triglyceride levels
Central Alpha-Adrenergic Receptor Agonists
*Dexmedetomidine*	Loading Dose IV: 1 mcg/kg over 10 min	Anxiolysis Analgesia Sedation	Onset: 5-10 min Side effects: Bradycardia, hypotension, loss of airway reflexes Half life: 1.8-3.1 hr. No active metabolites Intermittent bolus dosing is not recommended
	Continuous IV maintenance infusion: 0.2-0.7 mcg/kg/min		Maintenance infusion is adjusted to achieve desired level of sedation

Barr J, et al. Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Crit Care Med. 2013;41(1):278.

Targeted Sedation

All sedatives are to be administered to a specific target level identified by a RASS or SAS level appropriate to the patient’s clinical condition (Figure 10-1).² A target level is specified every day and reevaluated whenever there is a change in sedation dosage or patient condition. One likely sedation goal is that the patient is awake and calm, specified as a target sedation level of RASS = 0, or SAS = 4. This describes a patient who follows simple verbal commands without agitation and who can sustain eye contact for at least 10 seconds, as described in Table 10-1. When the intent is to provide deep sedation, the target sedation level is specified as RASS = -3 to -5 or SAS = 1 to 2.² This describes a mechanically-ventilated patient who is not responsive to voice, but who may respond to physical stimulation (see Table 10-1).

FIGURE 10-1 Agitation and Delirium Care Bundle.
*CAM-ICU*, Confusion Assessment Method for the Intensive Care Unit; *HTN*, hypertension; *ICDSC*, Intensive Care Delirium Screening Checklist; *NMB*, neuromuscular blockade; *RASS*, Richmond Agitation-Sedation Scale; *SAS*, Riker Sedation-Agitation Scale; *SBT*, spontaneous breathing trial. (From Barr J, Fraser GL, Puntillo KA, Ely WE, Gelinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. *Critical Care Medicine*. 2013, in press.)

Neuromuscular Blockade

Pharmacologic neuromuscular blockade (NMB) induces a state of physical paralysis. NMB is administered to achieve ventilator synchrony and improve oxygenation when this cannot be achieved by sedation and analgesia alone. Table 21-10 in Chapter 21 lists NMB medications, dosages, and management.

Because NMB causes a pharmacologic paralysis, the patient will not be able to respond to verbal or physical stimuli and additional monitoring methods are required. NMB is never administered unless adequate analgesia and sedation are also provided. This is because NMB paralyzes skeletal muscle but does not alleviate pain or confer sedation. It is vital that measures are in place to avoid a scenario where a patient who has received NMB cannot move, yet retains mental awareness.

Peripheral Muscle Monitoring.

A peripheral nerve stimulator (PNS) is used to assess paralysis of skeletal muscle as described in the section on neuromuscular blocking agents in Chapter 21. A PNS stimulator is shown in Figure 21-17.

Brain Function Monitoring.

Brain function monitoring is recommended to assess level of consciousness following NMB administration (see Figure 10-1).² In the operating room, brain function or activity is routinely monitored during anesthesia to ensure the patient does not have awareness during surgery. Similar monitoring technologies are now recommended for critically ill patients receiving NMB in addition to standard sedation assessments with RASS or SAS.² Various technologies are available that monitor the electrical activity of the brain frontal lobes and include electromyelogram (EMG) sensors to record forehead muscle movements.

Benzodiazepines

Benzodiazepines have powerful amnesic properties that inhibit reception of new sensory information.1,7 Benzodiazepines do not confer analgesia. The most frequently used benzodiazepines are diazepam (Valium), midazolam (Versed), and lorazepam (Ativan). Once a mainstay of sedation, benzodiazepines are no longer recommended for sedation of the mechanically ventilated critically ill adult.² This is because benzodiazepine-based sedative regimens are associated with worse patient outcomes, including longer duration of mechanical ventilation and delirium.^8–10

Short-acting benzodiazepines (midazolam) are still helpful for the treatment of acute short-term agitation,² because the intravenous (IV) onset of action is less than 3 minutes. However, when midazolam is administered for longer than 24 hours as a continuous infusion, the sedative effect is prolonged by its active metabolites.¹ Longer acting benzodiazepines (lorazepam and diazepam) also have a role in the management of delirium tremens (described later in the chapter) and seizures,² but these are different indications from routine sedation in critical illness.

The major unwanted side effects associated with benzodiazepines are dose-related respiratory depression and hypotension. If needed, flumazenil (Romazicon) is the antidote used to reverse benzodiazepine overdose in symptomatic patients. Flumazenil should be avoided in patients with benzodiazepine dependence, because rapid withdrawal can induce seizures.¹¹