The 2025 SCCM Focused Update to the PADIS (Pain, Anxiety, Agitation/Sedation, Delirium, Immobility, Sleep) Guidelines updates the landmark 2018 guidelines with new evidence on sedation selection, melatonin, enhanced mobilization, and anxiety management. Bottom line: dexmedetomidine over propofol when targeting light sedation, melatonin for sleep, and enhanced mobilization/rehabilitation are now formally recommended.
🔍 Overview
What Is PADIS?
Pain • Anxiety/Agitation • Delirium • Immobility • Sleep Disruption, the five domains of ICU suffering that drive morbidity, mortality, and post-ICU syndrome.
2025 vs 2018, What Changed:
• Dexmedetomidine suggested over propofol when light sedation and/or delirium reduction are priorities
• Melatonin now suggested for ICU patients (sleep quality + may reduce delirium)
• Enhanced mobilization/rehabilitation over usual care
• Anxiety added as a formal domain (new in 2025)
• Antipsychotics for delirium: no recommendation (insufficient evidence for benefit)
• All recommendations are conditional, individualize to each patient
The ABCDEF Bundle
The ICU Liberation ABCDEF Bundle operationalizes PADIS at the bedside. Each element should be assessed daily:
Key Change:PADIS, 2025, Dexmedetomidine is now suggested over propofol for sedation in mechanically ventilated adults where light sedation (RASS 0 to −2) and/or delirium reduction are highest priorities.
Recommendation
Strength
Certainty
Clinical Notes
Dexmedetomidine over propofol when light sedation or delirium reduction are priorities
Conditional
Low
Dexmedetomidine may reduce delirium incidence and improve time at target RASS. Higher risk of bradycardia. NOT appropriate for deep sedation (RASS −4/−5) or patients needing NMBAs.
Propofol remains appropriate for patients needing rapid on/off sedation or deep sedation
,
,
Faster wake-up for neuro checks and SAT/SBT. Monitor triglycerides q48h. Propofol infusion syndrome risk if > 80 mcg/kg/min > 48h.
Avoid benzodiazepines for routine ICU sedation
Conditional (2018)
Low
Associated with increased delirium, longer MV duration, longer ICU stay. Reserve for alcohol withdrawal, seizures, or benzodiazepine-dependent patients.
Analgesia-first approach
Conditional (2018)
Low
Treat pain before escalating sedation. Fentanyl infusion as first-line. Many patients appear "agitated" when actually in pain.
When to Choose What
Clinical Scenario
Preferred Agent
Rationale
Light sedation target (RASS 0 to −2)
Dexmedetomidine
Less delirium, preserves respiratory drive, cooperative sedation
Deep sedation needed (NMBAs, proning)
Propofol ± fentanyl
Titratable, rapid on/off. Dex inadequate for RASS −4/−5
Neuro checks needed frequently
Propofol
Fastest wake-up time for neurological assessment
Hemodynamically unstable / bradycardia risk
Propofol or fentanyl
Dex causes bradycardia and hypotension; avoid in shock
Alcohol withdrawal / seizure risk
Benzodiazepine (CIWA-guided)
Only appropriate indication for benzo ICU sedation
Post-extubation agitation / anxiety
Dexmedetomidine low-dose
Preserves airway reflexes; anxiolytic without respiratory depression
Daily Sedation Awakening Trial (SAT)
Protocol: Hold sedation each morning โ assess RASS โ if patient tolerates (RASS −1 to +1 without distress) โ proceed to SBT. If agitation/distress โ restart at 50% previous dose and titrate. ABC Trial, 2008: paired SAT + SBT reduced ventilator days by 3.1 days and 1-year mortality by 14%.
🧠 Delirium
Delirium: 2025 Update
2025 Key Finding: The PADIS task force was unable to recommend for or against antipsychotics for ICU delirium. Current evidence shows minimal or no effect on ICU/hospital length of stay. Focus on non-pharmacologic prevention first.
CAM-ICU Screening (Assess q8-12h)
Feature
Assessment
Positive If
1. Acute onset / fluctuating course
Change from baseline OR fluctuating mental status in past 24h?
Yes
2. Inattention
Squeeze my hand when I say "A", S-A-V-E-A-H-A-A-R-T
< 8/10 correct (errors > 2)
3. Altered consciousness
RASS score at time of assessment
RASS โ 0 (any score other than alert/calm)
4. Disorganized thinking
"Will a stone float on water?" "Are there fish in the sea?" + command
Correct sensory deficits, glasses, hearing aids at bedside
Family presence, familiar voices reduce agitation and disorientation
Music therapy, familiar music may reduce anxiety and agitation
Melatonin, now formally suggested PADIS, 2025
Pharmacologic Management
Drug
Dose
Evidence
2025 Status
Haloperidol (Haldol)
0.5–2 mg IV/IM q4-6h PRN
MIND-USA, 2018: no benefit on delirium duration or coma-free days
No recommendation for or against
Quetiapine (Seroquel)
25–200 mg PO BID
Limited evidence; may reduce delirium duration in small trials
No recommendation for or against
Dexmedetomidine
0.2–1.5 mcg/kg/hr IV
MENDS, 2009: less delirium vs midazolam. SEDCOM, 2009: less delirium (54% vs 76.6%) and shorter time to extubation vs midazolam. Now suggested over propofol.
Suggested over propofol (PADIS 2025)
Melatonin
3–5 mg PO at bedtime
Low-risk intervention; may improve sleep quality and reduce delirium incidence
Suggested (PADIS 2025, new)
Avoid: Benzodiazepines for delirium treatment (worsen delirium). Physical restraints should be minimized, they increase agitation and prolong delirium. QTc monitoring required for all antipsychotics.
🏃 Mobility & Sleep
Enhanced Mobilization (2025 Recommendation)
New:PADIS, 2025, Enhanced mobilization/rehabilitation is suggested over usual care. Enhancements include cycling, early initiation, twice-daily sessions, protocol-driven approaches, or extended duration.
Mobilization Levels
Level
Activity
When
0
Passive ROM in bed
Hemodynamically unstable, on NMBAs, high FiOโ
1
Active-assisted ROM in bed, bed exercises
On vasopressors but stable, mechanical ventilation
2
Sitting on edge of bed (dangle)
RASS ≥ −2, FiOโ ≤ 0.6, vasopressors weaning
3
Standing, transfer to chair
Cooperative, stable vitals, able to follow commands
4
Ambulation (with or without assist)
Off vasopressors, tolerating lower vent support or extubated
Safety Screen Before Mobilization
MAP < 60 or > 110, or new/escalating vasopressors
Active cardiac ischemia or unstable arrhythmia
SpOโ < 88% on current settings
Active seizures, raised ICP, or unstable spine
Active hemorrhage or unsecured airway
Patient refusal or extreme distress
Sleep Disruption
New:PADIS, 2025, Melatonin is now suggested for ICU patients. Low-risk intervention that may improve sleep quality and reduce delirium. Note: not FDA-regulated, so quality may vary between brands.
ICU Sleep Bundle
Environmental: Dim lights 10 PM–6 AM, minimize alarms, cluster care to allow 4h uninterrupted sleep
Pharmacologic: Melatonin 3–5 mg PO at 9 PM. Avoid benzos and zolpidem (worsen delirium)
Ventilator: Optimize settings to minimize discomfort/dyssynchrony at night
Sensory: Offer ear plugs and eye masks (shown to improve sleep quality in RCTs)
First-line analgesia. Less hypotension than morphine. Accumulates in renal/hepatic failure.
Dexmedetomidine (Precedex)
0.2–1.5 mcg/kg/hr IV
5–10 min
PADIS 2025 preferred for light sedation. Bradycardia risk. No respiratory depression. Anxiolytic.
Propofol (Diprivan)
5–50 mcg/kg/min IV
30–60 sec
Fastest wake-up. Monitor TGs q48h. Propofol infusion syndrome (PRIS) risk if > 80 mcg/kg/min > 48h. Best for neuro checks.
Midazolam (Versed)
0.02–0.1 mg/kg/hr IV
2–3 min
Avoid for routine sedation (โ delirium). Reserve for alcohol withdrawal/seizures. Accumulates.
Ketamine
0.1–0.5 mg/kg/hr IV
1–2 min
Opioid-sparing analgesic. Useful in refractory pain or bronchospasm. Emergence reactions.
Melatonin
3–5 mg PO at bedtime
30–60 min
PADIS 2025 new recommendation. Sleep promotion. May reduce delirium. Not FDA-regulated.
Haloperidol (Haldol)
0.5–2 mg IV/IM q4-6h PRN
10–20 min
No PADIS recommendation for delirium. QTc monitoring. Risk of EPS. Use only for acute safety threats.
Hypersalivation / Sialorrhea
Common in the ICU from ketamine infusions, clozapine, bulbar dysfunction (stroke, ALS, post-extubation weakness), or simply an inability to clear pooled oropharyngeal secretions. Listed most common to least common.
Drug
Dose
Key Points
Glycopyrrolate (Robinul)
0.1–0.2 mg IV q4–6h PRN, or 1–2 mg PO/NG TID
First-line in ICU. Does not cross the blood-brain barrier, so no delirium risk (unlike IV atropine or scopolamine). Workhorse for ketamine infusions, clozapine drooling, and post-extubation secretions.
Atropine 1% ophthalmic drops
1–2 drops sublingual q4–6h
Off-label but cheap and effective. Minimal systemic absorption. Useful when the patient cannot swallow pills.
Scopolamine patch (Transderm Scōp)
1.5 mg transdermal q72h
Convenient sustained effect but 6–12 h to onset. Avoid in elderly or already delirious patients (CNS anticholinergic effects).
Hyoscyamine (Levsin)
0.125 mg SL q4h PRN
Alternative when glycopyrrolate is unavailable.
Ipratropium
500 mcg nebulized q6h, or SL
Reserve for refractory cases or when other routes are limited.
Chronic or refractory sialorrhea only (bulbar ALS, Parkinson, cerebral palsy). Effect lasts ~3 months.
Address the cause: Ketamine infusion: glycopyrrolate premedication is standard. Clozapine: dose reduction or scheduled glycopyrrolate (do not abruptly stop clozapine). Organophosphate toxicity: atropine plus pralidoxime (different problem). Bulbar / neuro: glycopyrrolate plus Yankauer suction, head of bed up, swallow evaluation.
Watch for anticholinergic load: urinary retention, ileus, tachycardia, delirium, dry eyes. Stack carefully if the patient is already on other anticholinergics.
📋 On Rounds
Pimp Questions
What sedation agent does PADIS 2025 suggest over propofol, and when?
Dexmedetomidine is suggested over propofol when light sedation (RASS 0 to −2) and/or delirium reduction are the highest priorities. It reduces delirium incidence but carries higher risk of bradycardia. NOT appropriate for deep sedation or hemodynamic instability.
Does PADIS 2025 recommend antipsychotics for ICU delirium?
No. The task force was unable to issue a recommendation for or against antipsychotics for delirium treatment. MIND-USA, 2018 and other trials show minimal or no effect on ICU/hospital LOS. Focus on non-pharmacologic prevention: reorientation, sleep hygiene, early mobilization, minimizing deliriogenic meds.
What is the ABCDEF bundle and why does it matter?
A = Assess/prevent/manage pain, B = Both SAT + SBT daily, C = Choice of sedation (dex or propofol, avoid benzos), D = Delirium assess/prevent/manage, E = Early mobilization, F = Family engagement. Operationalizes PADIS guidelines at the bedside. Bundle compliance associated with lower mortality, less delirium, and shorter ICU stays.
When is propofol preferred over dexmedetomidine?
When deep sedation is required (RASS −4/−5 for NMBAs or proning), when frequent neuro checks need rapid wake-up, or when the patient has hemodynamic instability or bradycardia risk. Dex cannot achieve deep sedation and may worsen hypotension/bradycardia.
What does PADIS 2025 say about melatonin in the ICU?
Melatonin is now conditionally suggested for ICU patients (3–5 mg PO at bedtime). It is a low-risk intervention that may improve sleep quality and reduce delirium incidence. Caveat: melatonin is not FDA-regulated, so quality and bioavailability may vary between brands. Optimal dosing is still being studied.
Why should you avoid benzodiazepines for routine ICU sedation?
Benzodiazepines are independently associated with increased delirium (OR ~2–3x), longer duration of mechanical ventilation, longer ICU stay, and worse cognitive outcomes. PADIS, 2018 recommended non-benzodiazepine sedation. The only appropriate ICU indications are alcohol withdrawal (CIWA-guided), active seizures, and benzodiazepine-dependent patients.
What enhanced mobilization strategies does PADIS 2025 suggest?
Enhanced mobilization includes: in-bed cycling, early initiation (within 48h), twice-daily sessions, protocol-driven approaches, or extended duration of mobility. Schweickert, 2009: early PT/OT improved functional independence and reduced delirium duration. Goal is to mitigate ICU-acquired weakness and its long-term impact on survival and quality of life.
Daily ICU Sedation Checklist
RASS score, Current? At target (0 to −2)?
Pain assessment, CPOT/BPS. Analgesia adequate before sedation adjustment?
CAM-ICU, Delirium screen this shift?
SAT eligibility, Can we hold sedation today?
SBT eligibility, If SAT passed, ready for breathing trial?
Deliriogenic meds, Can we stop benzos, anticholinergics, unnecessary opioids?
Family, Visitation plan? Family meeting needed?
📋 Sample Presentation
"Mrs. Chen is on ICU day 3, intubated for ARDS. Sedation: dexmedetomidine at 0.8 mcg/kg/hr with fentanyl 75 mcg/hr. RASS is −1, at our target. CAM-ICU was negative this morning. We did a SAT, she tolerated the sedation hold and proceeded to an SBT, which she passed. Plan is to extubate today. PT had her dangling yesterday. Melatonin 3 mg at bedtime. No benzodiazepines. Family has been at bedside with open visitation."