1. Clinical Manifestations and Initial Diagnostic Assessment

Distinguish agitation from oversedation by combining behavioral observations with physiologic data to identify underlying causes and prevent complications.

A. Presentation of Agitation

• Behavioral cues: Restlessness, combativeness, attempts to remove tubes or catheters.
• Hemodynamic signs: Tachycardia, hypertension, diaphoresis, mydriasis.
• Ventilator asynchrony: High peak pressures, “bucking” the ventilator, frequent alarm triggers.

B. Presentation of Oversedation

• Respiratory: Hypoventilation, shallow breathing, rising PaCO₂ on arterial blood gas.
• Neurologic: Minimal or no response to voice or physical stimulation (RASS –4 to –5).
• Airway risk: Loss of protective cough and gag reflexes, increasing aspiration potential.

C. Differential Diagnoses

• Inadequate analgesia or uncontrolled pain
• Delirium (hyperactive, hypoactive, or mixed)
• Withdrawal syndromes (alcohol, benzodiazepines, opioids)
• Acute neurologic events (intracranial hemorrhage, ischemic stroke)
• Metabolic encephalopathies (electrolyte disturbances, hepatic/renal failure)

2. Diagnostic Modalities

Laboratory, imaging, and neurophysiologic tools help confirm etiology and tailor sedation strategies.

A. Essential Laboratory Tests

• Electrolytes: Na, K, Ca, Mg (detect osmolar shifts, seizure risk)
• Glucose: Hypo- or hyperglycemia can mimic agitation or lethargy
• Renal/hepatic panels: Guide drug clearance and detect encephalopathy
• Inflammatory markers: WBC count, CRP, procalcitonin for sepsis-related delirium
• Arterial blood gas: Assess ventilation (PaO₂, PaCO₂) and acid–base status
• Lactate: Evaluates tissue perfusion and shock states

B. Imaging Studies

• Head CT: Rapid exclusion of hemorrhage, mass effect, hydrocephalus.
• Brain MRI: Sensitive for ischemia, demyelination, posterior reversible encephalopathy.
• Point-of-care ultrasound (POCUS): Optic nerve sheath diameter as a surrogate for intracranial pressure. (Editor’s Note: limited ICU validation—sensitivity/specificity data needed)

C. Neurophysiologic Monitoring

• Continuous EEG: Gold standard for nonconvulsive seizure detection and burst suppression titration.
• Bispectral index (BIS): Processed EEG index (0–100) correlating with sedation depth under paralysis. Limitations include EMG artifacts, ketamine effects, and limited validation in non-paralyzed patients.

3. Classification Systems and Severity Scoring

Apply validated scales to quantify arousal and delirium, then integrate general severity scores for prognostication.

A. Sedation Scales

• Richmond Agitation-Sedation Scale (RASS): +4 (combative) to –5 (unarousable). Target for light sedation: RASS –2 to 0.
• Sedation-Agitation Scale (SAS): 1 (unarousable) to 7 (dangerous agitation).

B. Agitation-Specific Tool

• Motor Activity Assessment Scale (MAAS): 0 (no response) to 6 (dangerous agitation).

C. Delirium Screening

• Confusion Assessment Method for the ICU (CAM-ICU): Assesses acute change, inattention, disorganized thinking, and altered consciousness; valid if RASS ≥ –3.
• Intensive Care Delirium Screening Checklist (ICDSC): An eight-domain checklist where a score ≥4 indicates delirium.

D. General Severity Scores

• APACHE II/IV and SOFA: Quantify organ dysfunction and mortality risk; correlate with delirium incidence but are not designed for sedation titration.

4. Diagnostic Workflow and Decision Algorithms

A structured, stepwise approach streamlines the evaluation of abnormal arousal and triggers advanced diagnostics appropriately.

5. Practice Nuances and Pitfalls

Recognize tool limitations and avoid overreliance on single data points; maintain thorough documentation for continuity of care.

Common Pitfalls

• Misinterpreting mild lab abnormalities without clinical correlation.
• Overreliance on BIS monitoring during ketamine administration or in the presence of EMG interference.
• Applying delirium screening tools (CAM-ICU, ICDSC) to patients who are deeply sedated (RASS ≤ –4), as the results are invalid.
• Ordering unnecessary imaging in low-risk, clinically stable patients without a clear indication.

Documentation Best Practices

• Chart RASS and CAM-ICU or ICDSC scores at regular intervals (e.g., every 4 hours).
• Note differential diagnoses and the clinical rationale for any sedation adjustments.
• Use structured EHR templates to ensure accurate and complete handoffs between care teams.