ICU Analgesia, Sedation and Delirium (PADIS)

Analgosedation starts with pain. Treat it first, and add a sedative only if the patient still needs one. The goal is an intubated ICU patient who is comfortable, safe and moving with the ventilator, not one who is knocked out. That covers four things: which analgesic and which sedative, how deep to sedate, how to screen for delirium, and when to stop sedation each day. Light sedation is the default. Go deeper only when a specific indication calls for it.

Key Components

Flow Path

1. Assess pain with the unit scale (CPOT or BPS) before any sedative change.
2. Treat pain first: an opioid base, with non-opioid adjuncts and non-drug measures per protocol, then reassess. Add a sedative only if agitation or dyssynchrony persists after pain is treated.
3. Set a RASS goal in the order, usually −2 to +1, and run the lowest infusion rate that meets it.
4. Screen for delirium with CAM-ICU and correct its causes before adding drugs.
5. Stop sedative infusions once a day when safe, then run a spontaneous breathing trial if the patient passes.
6. Mobilize early and involve family in the plan.

What It Does

What It Depends On

• Pain control: pain that goes untreated pushes up both the agitation and the sedative a patient needs
• Volume and vasopressor status: a patient low on volume drops further on propofol or an alpha-2 agent
• Liver and kidney function: they change clearance, and with it how long the drug lasts
• Other CNS depressants: stacking opioids on benzodiazepines adds respiratory depression to the mix
• Ventilator synchrony and airway: a patient fighting the vent looks agitated, and that tempts you to over-sedate

Why Alpha-2 Agents Differ

Dexmedetomidine binds alpha-2 receptors more selectively than clonidine, and it has the bigger evidence base. Clonidine clears less predictably in critical illness. Both drugs quiet the sympathetic drive. That same quieting is behind most of their bradycardia and hypotension.

Ventilated adults get sedation one of three ways: a titrated continuous infusion aimed at a RASS goal, short intermittent doses for short needs, or a mix of both. Analgesia usually comes as intermittent opioid doses or as an infusion.

Sedation Modes

• Light continuous infusion: the default for ventilated adults, titrated to a RASS goal
• Intermittent IV doses: for short, predictable needs such as a painful dressing change or agitation episode
• Nurse-driven protocol: pre-set titration steps and stop rules, written by the ICU
• Deep sedation or neuromuscular blockade: only for a specific indication, with a defined endpoint and reassessment
• Benzodiazepines: reserved for specific indications such as alcohol or benzodiazepine withdrawal or seizures, or when propofol and dexmedetomidine are unsuitable, per protocol

Analgesia-First, Opioid-Sparing Care

• Analgesia first: PADIS puts pain treatment ahead of sedation. Add a sedative only once the pain is treated and the agitation is still there.
• Multimodal: scheduled acetaminophen, low-dose ketamine and regional or local options bring the opioid need down, per protocol.
• Opioid infusions: start low and titrate to the pain score. The fentanyl label gives no ICU infusion range, so protocol sets the rate (see the fentanyl page). Hydromorphone and morphine follow their own pages and their own protocol.
• Non-drug measures: reposition, splint before moves, treat bladder distension and constipation, and keep family involved.
• Daily SAT: on awakening-trial day the sedative infusions pause. Analgesia keeps running, unless the order says otherwise.

Indications

• Pain from injury, surgery or procedures in an intubated adult who cannot report pain well
• Agitation or ventilator dyssynchrony that threatens the airway, lines or safety after pain, hypoxia, bladder distension and withdrawal are addressed
• Light sedation of intubated adults on mechanical ventilation, with the RASS goal set in the order
• Neuromuscular blockade only for a specific indication such as severe ARDS, per local protocol and with sedation running (see Alarms and Special Populations)
• Deeper sedation only for a named indication under specialist protocol, such as raised ICP or TBI, seizures with neurology input, or alcohol or benzodiazepine withdrawal

Contraindications

Limitations

Switching agents will not shorten time on the ventilator by itself. In the A2B trial, dexmedetomidine and clonidine did no better than propofol for time to extubation. The dexmedetomidine label caps ICU infusions at 24 hours. Longer exposure may bring tolerance, tachyphylaxis and more adverse events, and stopping can cause withdrawal (label). Going past 24 hours is off-label and per protocol.

Key Evidence

The 2025 PADIS update came out before the A2B results. Its dexmedetomidine recommendation and the A2B finding both still stand, so this page reports both.

Targets

Initial Settings

• Propofol: start 5 mcg/kg/min (0.3 mg/kg/hr) for at least 5 minutes; raise in steps of 5–10 mcg/kg/min over 5–10 minutes to the goal (label). Each mL carries 1.1 kcal of lipid, so count it in the nutrition plan. Use strict aseptic technique: complete each vial within 12 hours of spiking, and discard tubing and unused drug after 12 hours (label)
• Dexmedetomidine: 1 mcg/kg IV over 10 minutes, then 0.2–0.7 mcg/kg/hr (label ICU range). The load is often omitted per protocol, especially when converting from another sedative
• Midazolam (typical; follow institutional protocol): 0.02–0.1 mg/kg/hr (1–7 mg/hr in adults), with an optional load of 0.01–0.05 mg/kg
• Fentanyl (intermittent): 25–100 mcg IV as needed (label maintenance range); interval and titration per protocol (see the fentanyl page)

Write the dosing weight on every weight-based order: actual, ideal or adjusted, per protocol. Protocols differ for obesity. The same mg/kg number can mean a very different total dose.

Post-Intubation Analgosedation (First Hour)

1. Start analgesia as soon as the tube is confirmed and secured, not after the paralytic wears off. In the rocuronium label, 0.6 mg/kg gives a median of about 31 minutes of clinical relaxation (range 15–85, under opioid and nitrous oxide anesthesia), and larger doses last longer (rocuronium page), so a patient can be aware and unable to show it.
2. Choose by blood pressure. With a normal pressure, give analgesia plus a sedative per protocol, for example fentanyl with a midazolam bolus starting at 1 mg IV slowly and titrated to effect (protocol-dependent). When the patient is hypotensive or shock is likely, reduce every dose and check blood pressure at least every 5 minutes. The ketamine dose here (0.1–0.3 mg/kg IV over 10–15 minutes, max 0.35 mg/kg per bolus) and the fentanyl dose (1 mcg/kg IV slowly, max 100 mcg for the first dose) are analgesic doses only (ketamine and fentanyl pages). Neither one reliably gives sedation, and fentanyl gives no amnesia. A patient paralyzed with rocuronium still needs a sedative-amnestic agent, so an opioid alone is not adequate sedation after a long-acting paralytic. Choose one of these, per protocol and with medical direction: (a) ketamine at a sedative dose: the Ketalar label gives an IV induction range of 1 to 4.5 mg/kg (average 2 mg/kg), and some shock protocols use a reduced dose near the low end of that range (protocol-dependent, not verified here). This is off-label for ICU sedation and is protocol-dependent, not a guideline recommendation (ketamine page); or (b) a reduced-dose midazolam bolus, starting at 1 mg IV slowly and not above 2.5 mg in a healthy adult, titrated to effect, only with analgesia already running (midazolam label: lower doses for older or debilitated patients and those receiving narcotics). Midazolam lowers blood pressure, and the midazolam page lists shock and SBP below 90 mmHg as reasons to hold sedation, so confirm this choice with medical direction before giving it.
3. Wait between doses. IV fentanyl acts within 1–2 minutes and IV midazolam within 3–5 minutes (medication pages), so reassess before repeating. Midazolam bolus dosing is 1–2.5 mg IV slowly, titrated, and only with analgesia already running (midazolam page).
4. Monitor continuously: ECG, SpO₂ and EtCO₂ with waveform capnography to confirm tube position and ventilation; blood pressure at least every 5 minutes; ventilator or bag rate and synchrony; pain score and RASS after each dose.

Propofol infusions are for critical care teams with a protocol and monitoring in place (CCT or ICU-trained, per protocol). Do not start one in the field without an order.

Scoring Tools

Pain tools: Use the tool your unit has validated. CPOT scores facial expression, body movements, muscle tension and ventilator compliance (or vocalization if not intubated), each 0–2, for a total of 0–8. A score of 3 or more is a commonly used threshold for treatment. The Behavioral Pain Scale (BPS) scores facial expression, upper limb movement and ventilator compliance, each 1–4, for a total of 3–12. Above 5 is a commonly used pain threshold.

CAM-ICU (delirium): a positive screen needs features 1 and 2, plus either feature 3 or feature 4: (1) acute change or fluctuating course; (2) inattention; (3) altered level of consciousness (RASS other than 0); (4) disorganized thinking.

Positioning & Mobility

Early mobility is part of the ABCDEF bundle. Get patients moving as soon as it is safe, and keep sedation light enough that they can take part. If they are sedated deeper than the goal, that is a reason to lighten the sedation, not a reason to skip mobility. PADIS 2025 conditionally recommends enhanced mobilization and rehabilitation over usual care.

Sleep

PADIS 2025 conditionally recommends melatonin for sleep in adult ICU patients. Check the unit protocol before you order it, and keep the non-drug sleep measures going alongside it.

Lipids

Propofol is an oil-in-water emulsion, built from soybean oil and egg phospholipid. Long use can push triglycerides up, according to the label. In at-risk patients, check triglycerides or serum turbidity. If the fat is not clearing, cut the dose or switch the sedative. See the triglycerides lab page.

Bleeding

None of the sedatives on this page treats or reverses bleeding. Run anticoagulation on its own pathway, and use the heparin page for monitoring and reversal.

Doses vary by protocol; follow local protocols and medical direction. Infusion rates are weight-based and come in four different units (mcg/kg/min, mcg/kg/hr, mg/kg/hr and mg/hr), and mixing them up is a common source of error.

Non-opioid adjunct: for adults of 50 kg or more, acetaminophen IV is 1,000 mg over 15 minutes every 6 hours, with a maximum of 4,000 mg per 24 hours from all sources. Lower weight-based limits and hepatic caution apply. See acetaminophen IV.

Rocuronium and the other neuromuscular blockers are not routine sedatives. Reach for one only for a specific indication, and only with train-of-four monitoring and sedation running. See the rocuronium page.

Readiness Criteria

• Pain controlled on scheduled or as-needed analgesia
• RASS at goal (−2 to +1 usually) on the lowest sedation rate
• No neuromuscular blocker running
• Stable hemodynamics without escalating vasopressors
• Delirium screen addressed; causes corrected

Weaning Steps

1. Run a daily spontaneous awakening trial when criteria are met: pause sedative infusions.
2. If the patient passes the awakening trial, start a spontaneous breathing trial per protocol (the ABC approach).
3. Taper dexmedetomidine or benzodiazepine infusions per protocol; the dexmedetomidine label reports withdrawal events after stopping.
4. Reassess pain before the first breathing trial.
5. Move to extubation criteria once the breathing trial is passed.

Failure Criteria: Step Back Up

If the patient shows marked agitation, tachypnea, dyssynchrony, distress or a new arrhythmia during the trial, restart sedation at the last effective rate. Look for pain and causes first, then restart lower.

Removal & Post-Removal Care

Once the infusions are off, keep watching RASS, pain and CAM-ICU until the patient is stable. Record how long it takes from stopping to the first awake response, and note the delirium status at every assessment.

Before You Move

1. Confirm analgesia and sedation are running at the current rate, with a labeled spare syringe or bag.
2. Check battery minutes and the pump with its own power source.
3. Label each infusion with drug, concentration and units (mcg/kg/min or mg/hr).
4. Pack airway equipment, naloxone and the reversal agent per protocol.
5. Brief the receiving team on the sedation goal, the last RASS and the last dose.

If You Are Not the ICU Clinician

• What to watch: breathing, RASS, pain, MAP and HR
• What not to touch: the rate on an infusion without an order or a second check
• Who to call: the ICU or transport physician for any drop in breathing or pressure
• CPR and defibrillation: stop the infusion first; treat per ACLS, and check for pulses with the pump in view

During Transport

Hold the sedation goal steady through the move. Pain and cold can set off sudden agitation, so treat the pain before you touch the rate. Check the line and the pump after every bump, turn or carrier change.

Air Medical & Altitude

Before takeoff, check the altitude and flight-mode settings on each pump. Carry spare batteries and infusion sets.

Handoff

• Sedation and analgesia drugs, concentrations and current rates
• Last RASS, pain score and CAM-ICU result
• Time and dose of the last bolus or opioid
• Recent alarms, hypotension or bradycardia episodes
• Airway and line sites, plus the goal of care

Pediatric & Neonatal

PICU sedation is largely off-label and protocol-driven. The propofol label says it is not indicated for pediatric ICU sedation, and it warns that propofol infusion syndrome has been reported with pediatric ICU infusions. The dexmedetomidine label covers ICU sedation in adults and procedural sedation of non-intubated children from 1 month to under 18 years. It does not cover PICU sedation. PICU teams often pair an opioid with dexmedetomidine or midazolam, dosed by weight per protocol. See weight-based dosing.

Opioid or benzodiazepine infusions that run for days, not hours, can cause iatrogenic withdrawal. Taper per protocol, and watch for tachycardia, agitation, tremor and gut upset. The 2022 SCCM pediatric guideline covers pain, sedation, withdrawal and delirium in critically ill children. Neonates need specialist dosing. The lorazepam label warns of benzyl alcohol toxicity in neonates and preterm infants.

Pregnancy & Peripartum

The Diprivan label reports data from trials, cohorts and case series over several decades. None shows a drug-associated pattern of major birth defects or miscarriage, though most exposures happened at cesarean delivery. The dexmedetomidine label reports no drug-associated risk, and its reported exposures mostly came after the first trimester. Involve obstetrics early. Late pregnancy raises aspiration and airway risk, so plan the airway and sedation with the obstetric team. Use left uterine displacement during resuscitation or transport, per obstetric protocol. Benzodiazepines given late in pregnancy can cause neonatal sedation and withdrawal (lorazepam label), so use the lowest dose for the shortest time.

Older and Frail Adults

In older, frail or debilitated patients, start low, titrate slowly and watch closely for bradycardia and hypotension. The dexmedetomidine label advises considering a dose reduction for patients over 65.

Liver and Kidney Failure

Liver or kidney failure changes how drugs clear. Reassess the RASS after each change, and do not stack doses. Ask pharmacy to review every sedative against the patient's organ function.

On ECMO or CRRT

Circuits can sequester drugs and change how they clear, so doses may need to change. For circuit-related drug effects, and for who to call, see the ECMO page.

Systematic Walk-Through

1. Indication: why does this patient need sedation rather than analgesia alone?
2. Pain: what is the score, and what analgesic is running?
3. Sedation: which agent, what RASS goal and what current rate?
4. Delirium: CAM-ICU result and treatable causes?
5. Safety: MAP, HR, breathing, airway and line checks?
6. Stop: is a daily awakening trial due today?
7. Goal: mobility and family plan for today.

Pearls

• Treat the pain first. Most agitation settles once the pain is treated.
• Light sedation is the default. Going deeper needs a reason.
• Know where propofol and dexmedetomidine differ: bradycardia, lipid load and agitation.
• Many infusion errors are unit mix-ups, such as mcg/kg/min read as mg/hr.
• A paralyzed patient can still be aware. Sedation has to keep running.