Advanced Pharmacology · Topic 4 of 13

ICU Sedation & Analgesia

Critical care · PADIS sedation & analgesia

ICU Sedation & Analgesia

Treat pain first, then sedate lightly with propofol or dexmedetomidine rather than benzodiazepines — and watch long, high-dose propofol for infusion syndrome.

Key numbers

Target light sedation, not deepRASS −2 to +1

Propofol infusion syndrome: acidosis, hyperkalemia, rhabdomyolysis> 5 mg/kg/h for > 48 h

01 · FirstTreat pain before giving a sedative

Guide ICU pain management by routine pain assessment and treat pain before a sedative is considered (analgesia-first sedation), usually with an opioid, inside an assessment-driven, protocol-based stepwise approach.

02 · The ruleTarget light sedation, not deep

Use light rather than deep sedation in mechanically ventilated adults — a calm patient who opens the eyes to voice; PADIS trials defined light sedation as RASS −2 to +1.

03 · GivePropofol or dexmedetomidine over benzodiazepines

Sedate ventilated adults with propofol or dexmedetomidine rather than a benzodiazepine (PADIS 2018); the 2025 focused update conditionally suggests dexmedetomidine over propofol. Benzodiazepines carry more delirium.

Diagnosis & monitoring

Work-up

Assess pain with NRS, or BPS/CPOTUse the patient's self-report on a 0–10 numeric rating scale when possible; in patients who cannot self-report but have observable behaviors, use the Behavioral Pain Scale or the Critical-Care Pain Observation Tool.

Propofol is fat: check triglyceridesPropofol is a lipid emulsion (about 1.1 kcal/mL): count it in nutrition and check triglycerides about every 48 hours once infusions exceed 24–48 hours; it is contraindicated with anaphylaxis to egg or soy.

Measure sedation with RASS or SASTitrate sedatives to a goal on a validated scale — the Richmond Agitation-Sedation Scale or Riker Sedation-Agitation Scale — reassessed regularly, rather than to an unmeasured clinical impression.

Do right now

In this order

First moves

Assess pain with NRS, or BPS/CPOT

→

Treat pain before giving a sedative

→

Target light sedation, not deepRASS −2 to +1

→

Interrupt sedation daily, restart at half dose

Why each step

Treat pain before giving a sedativeGuide ICU pain management by routine pain assessment and treat pain before a sedative is considered (analgesia-first sedation), usually with an opioid, inside an assessment-driven, protocol-based stepwise approach.

Target light sedation, not deepUse light rather than deep sedation in mechanically ventilated adults — a calm patient who opens the eyes to voice; PADIS trials defined light sedation as RASS −2 to +1.

Interrupt sedation daily, restart at half doseInterrupt sedative infusions daily until the patient is awake and following commands (or needs re-sedation), restart at half the previous dose if still needed, and then screen for a spontaneous breathing trial.

Management

Orders

Dexmedetomidine: arousable sedation, causes bradycardia must knowDexmedetomidine, an α2 agonist (0.2–0.7 mcg/kg/h), leaves patients rousable with stimulation and can run through extubation; its main adverse effects are bradycardia, sinus arrest and hypotension.

Avoid morphine in renal failureMorphine's active glucuronide metabolites accumulate in renal failure (sedation, respiratory depression, myoclonus) and meperidine's normeperidine causes seizures; fentanyl releases less histamine and causes less hypotension.

Add multimodal adjuncts to spare opioidsAdd acetaminophen to opioids, consider low-dose ketamine as an analgesic adjunct after surgery (PADIS: 0.5 mg/kg, then 1–2 mcg/kg/min, about 0.06–0.12 mg/kg/h), and use gabapentin, pregabalin or carbamazepine for neuropathic pain (strong recommendation).

Propofol: start 5 mcg/kg/min, watch hypotensionStart propofol at 5 mcg/kg/min and titrate by 5–10 mcg/kg/min every 5 minutes or more; most patients need 5–50 mcg/kg/min, and higher rates bring hypotension. Do not exceed 4 mg/kg/h unless benefit outweighs risk.

Dexmedetomidine load is optionalA dexmedetomidine load (1 mcg/kg over 10 minutes) may be omitted when converting from another sedative and causes transient hypertension; reduce doses in older adults and hepatic impairment.

Agitated delirium blocking extubation: dexmedetomidineWhen agitated delirium is preventing weaning or extubation in a ventilated adult, PADIS suggests dexmedetomidine; antipsychotics and dexmedetomidine are not used to prevent delirium in all patients (see Delirium).

Red flags & don'ts

Avoid harm

Propofol infusion syndrome: acidosis, hyperkalemia, rhabdomyolysis complicationPropofol infusion syndrome — severe metabolic acidosis, hyperkalemia, lipemia, rhabdomyolysis, Brugada-like ECG, renal and cardiac failure — risk rises above 5 mg/kg/h for over 48 hours, with sepsis, brain injury, vasopressors or steroids. Stop propofol.

Benzodiazepine infusions accumulate complicationMidazolam (CYP3A4 metabolism) has an active metabolite, 1-hydroxymidazolam, and a prolonged half-life in renal failure; high-dose lorazepam infusions can cause propylene glycol toxicity (lactic acidosis, hyperosmolality, hypotension).

Propofol or dexmedetomidine?

Commonly confused

Usual ICU dose	5–50 mcg/kg/min
Main hemodynamic effect	Hypotension
Signature risk	Propofol infusion syndrome, high triglycerides
Around extubation	No abrupt stops; keep light through weaning

More detail

Reference

Show 6 reference facts

Propofol (with EDTA) chelates zinc: avoid infusions longer than 5 days without a drug holiday, and consider zinc supplements in burns, diarrhea or major sepsis.

Dexmedetomidine is labeled for infusions up to 24 hours; longer exposure may bring tolerance, tachyphylaxis and withdrawal on stopping.

Dose propofol, dexmedetomidine, midazolam and opioids on ideal or adjusted body weight in severe obesity, titrating to effect (see Severe Obesity in Acute Care).

The 2025 PADIS update made no recommendation on benzodiazepines to treat anxiety in ICU adults; it conditionally suggests melatonin for sleep.

Neuromuscular blockade requires continuous deep sedation and analgesia given first — paralysis without adequate sedation risks awareness (see RSI Drugs & Neuromuscular Blockers).

Do not stop propofol abruptly before weaning or a daily sedation assessment (rapid awakening with agitation and ventilator resistance); keep sedation light through weaning — titrated to the minimum, patients awaken within 10–15 minutes.

Pearl

Analgesia first, sedation light — an awake, comfortable patient gets off the ventilator sooner.

Sources · Devlin JW 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 (PADIS). Crit Care Med 2018;46:e825–e873 · Lewis K et al. A Focused Update to the PADIS Clinical Practice Guidelines (anxiety, agitation/sedation, delirium, immobility, sleep). Crit Care Med 2025 (abstract via Europe PMC) · Diprivan (propofol) injectable emulsion prescribing information — DailyMed (§2.6 ICU sedation; §5.9 propofol infusion syndrome; §5.10 triglycerides; §5.11 zinc) · Precedex (dexmedetomidine) prescribing information — DailyMed · Midazolam injection prescribing information — DailyMed (clinical pharmacology: CYP3A4, 1-hydroxymidazolam, renal failure) · Ativan (lorazepam) injection prescribing information — DailyMed (propylene glycol toxicity) · Merck Manual Professional — Overview of Mechanical Ventilation (sedation and comfort; neuromuscular blockade) · Merck Manual Professional — Medications to Aid Intubation (post-intubation sedation; benzodiazepines and delirium) · Merck Manual Professional — Treatment of Pain (table: opioid analgesics) · Merck Manual Professional — Liberation from Mechanical Ventilation (daily sedation interruption, restart at half dose, then SBT) · Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient — a focus on sedation, analgesia, and delirium. Crit Care 2020;24:315 · Renew JR et al. Neuromuscular blockade management in the critically ill patient. J Intensive Care 2020;8:37 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).