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ICU Sedation, Analgesia & Delirium

Name: ICU Sedation, Analgesia & Delirium
Creator: Veli Bakalov, MD

Treat pain first, sedate lightly, hunt for delirium

Emergency & Critical Care·Critical Care·5 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Treat pain first: fentanyl or hydromorphone titrated to a behavioral pain score (CPOT or BPS), then add a sedative only if agitation persists.
Keep ventilated patients light (RASS 0 to −2) and pair a daily spontaneous awakening trial with a spontaneous breathing trial.
Propofol: fast offset but hypotension, hypertriglyceridemia/pancreatitis, and propofol infusion syndrome (lactic acidosis, rhabdomyolysis, hyperkalemia, bradyarrhythmia) — stop the infusion.
Dexmedetomidine (central α2 agonist): arousable sedation without respiratory depression and less delirium, at the cost of bradycardia and hypotension.
Benzodiazepines independently raise delirium risk: reserve them for alcohol or sedative withdrawal, seizures, and amnesia during paralysis.
Ketamine (NMDA antagonist) preserves airway reflexes, breathing, and blood pressure and bronchodilates — useful in hypotension or status asthmaticus.
CAM-ICU positive = acute/fluctuating course + inattention + (altered consciousness or disorganized thinking); hypoactive delirium is the most common and most missed.
ABCDEF bundle prevents delirium and PICS; antipsychotics are only for agitation that endangers the patient.
Procedural sedation runs minimal → moderate → deep → general anesthesia; capnography detects apnea before the pulse oximeter falls.

Analgesia first, sedation light

Analgosedation. Pain from the endotracheal tube, suctioning, turning, and wounds drives most agitation and ventilator dyssynchrony, so treat pain first and add a hypnotic only if agitation persists. Patients who cannot self-report are scored with a behavioral tool: the Critical-Care Pain Observation Tool (CPOT) or the Behavioral Pain Scale (BPS).

Opioids. Fentanyl (rapid onset, no histamine release) and hydromorphone are the usual agents. Morphine is less attractive: histamine release causes hypotension, and its active metabolite (morphine-6-glucuronide) accumulates in kidney failure. Acetaminophen, low-dose ketamine, and regional blocks spare opioids.

Depth target. The Richmond Agitation-Sedation Scale (RASS) runs from +4 (combative) through 0 (alert and calm) to −5 (unarousable). Most ventilated adults are kept at RASS 0 to −2, which means at least brief eye contact to voice. Early deep sedation is linked to longer ventilation, more delirium, and higher mortality.

Daily interruption. A spontaneous awakening trial paired with a spontaneous breathing trial shortens mechanical ventilation and ICU stay. Defer the awakening trial during active seizures, alcohol withdrawal, neuromuscular blockade, raised intracranial pressure, or ongoing myocardial ischemia.

The sedative agents

Propofol or dexmedetomidine is preferred over benzodiazepines for routine sedation of ventilated adults.

ICU sedatives compared

Agent	Mechanism	Strengths	Key toxicities
Propofol	GABA-A agonist	Onset <1 min, offset in minutes; permits neuro checks; light or deep sedation	Hypotension, respiratory depression, no analgesia, hypertriglyceridemia and pancreatitis, PRIS
Dexmedetomidine	Central α2 agonist (locus coeruleus)	Arousable, cooperative sedation; no respiratory depression; opioid-sparing; less delirium	Bradycardia, hypotension; cannot produce deep sedation
Benzodiazepines	GABA-A agonist	Amnesia, anticonvulsant, treat alcohol and sedative withdrawal	Delirium, accumulation, prolonged ventilation
Ketamine	NMDA receptor antagonist	Dissociation with analgesia; preserves airway reflexes, breathing, and BP; bronchodilates	Emergence reactions, hypersalivation, rare laryngospasm, tachycardia and hypertension

Propofol. Rapid awakening makes it ideal when frequent neurologic examinations are needed. Its lipid vehicle supplies about 1.1 kcal/mL (count it as nutrition), and triglycerides are followed on prolonged infusions because hypertriglyceridemia can cause pancreatitis.

Propofol infusion syndrome (PRIS). High-dose (>4 mg/kg/h), prolonged (>48 h) infusions, especially with catecholamines or glucocorticoids, impair mitochondrial fatty-acid oxidation: severe lactic acidosis, rhabdomyolysis, hyperkalemia, hypertriglyceridemia, acute kidney injury, and bradyarrhythmias (sometimes a Brugada-like ECG) progressing to cardiovascular collapse. Stop propofol immediately; support with hemodialysis, pacing, or ECMO.

Dexmedetomidine. Because breathing is spared, it can run in non-intubated patients and through extubation, and it causes less delirium than benzodiazepines.

Benzodiazepines. Midazolam and lorazepam are reserved for alcohol or sedative withdrawal, seizures, and amnesia during neuromuscular blockade; otherwise they prolong ventilation and independently raise delirium risk. Midazolam's active metabolite accumulates in renal failure, and lorazepam infusions deliver propylene glycol, causing an anion-gap metabolic acidosis with a high osmolal gap.

Ketamine. Its sympathomimetic and bronchodilating effects suit hypotension and status asthmaticus; use caution in coronary disease.

ICU delirium

Definition and cost. Delirium is an acute, fluctuating disturbance of attention and awareness. Each delirium day is linked with higher mortality, longer ventilation, and long-term cognitive impairment.

Check arousalRASS −3 or lighter can be assessed; RASS −4 or −5 is coma, so reassess later.
Feature 1Acute change from baseline or fluctuating course.
Feature 2Inattention: squeeze only on the letter A; more than 2 errors is positive.
Feature 3 or 4Altered consciousness (any RASS other than 0) or disorganized thinking.
ResultFeatures 1 + 2 + (3 or 4) = CAM-ICU positive.

CAM-ICU step by step

Subtypes. Most ICU delirium is hypoactive or mixed: quiet, withdrawn, and easily misread as sedation or depression. Pure hyperactive delirium is uncommon, so screen every shift.

Risk factors. Nonmodifiable: older age, dementia, severe illness. Modifiable: benzodiazepines, anticholinergics (diphenhydramine, scopolamine), deep sedation, sleep disruption, immobility and restraints, and untreated pain. First correct reversible causes: hypoxemia, hypoglycemia, sepsis, urinary retention, and drug or alcohol withdrawal.

Prevention and treatment

A: assess, prevent, and manage pain
B: both spontaneous awakening and breathing trials
C: choice of analgesia and sedation (light, no benzodiazepines)
D: delirium assessment and management
E: early mobility and exercise
F: family engagement

Nonpharmacologic care. Reorient often, return glasses and hearing aids, protect night-time sleep from light and noise, avoid restraints, and mobilize even while intubated.

Antipsychotics. Haloperidol and atypical agents neither prevent nor shorten ICU delirium. Brief, low-dose use is reserved for agitation that endangers the patient or staff, such as self-extubation or pulling lines, with QTc monitoring. Calm delirium is managed by treating precipitants and nonpharmacologic measures.

Do not treat ICU delirium with a benzodiazepine unless alcohol or sedative withdrawal is the cause.

Post-intensive care syndrome (PICS). Survivors often have new physical (ICU-acquired weakness), cognitive, and psychiatric (depression, anxiety, PTSD) impairment that persists after discharge; relatives can develop PICS-F. The ABCDEF bundle is the main preventive lever.

Procedural sedation in the emergency department

The sedation continuum

Level	Responsiveness	Airway and breathing
Minimal (anxiolysis)	Normal response to voice	Unaffected
Moderate	Purposeful response to voice or touch	No intervention needed
Deep	Purposeful response only to repeated or painful stimuli	May need support; ventilation may be inadequate
General anesthesia	Unarousable, even to pain	Intervention often required

Monitoring. Waveform capnography shows hypoventilation (rising end-tidal CO₂) and apnea or obstruction (loss of the waveform) before saturation falls, a lag that is longest on supplemental oxygen. Respond with stimulation, jaw thrust, and bag-mask ventilation; propofol has no reversal agent, whereas midazolam and fentanyl can be reversed with flumazenil and naloxone.

Be ready to rescue a patient one level deeper than intended; the patient's response, not the dose, defines the level.