Sedation and Analgesics in ICU: Drug Regimen and Dose
Core Principle: Analgesia-First Strategy
Treat pain before administering any sedative agent—this is the fundamental cornerstone of modern ICU sedation management and directly improves mortality and morbidity. 1, 2
The analgesia-first approach (analgosedation) prioritizes pain control using opioids before considering sedatives, targets light sedation when possible, uses short-acting agents, and avoids benzodiazepines to reduce delirium, mechanical ventilation duration, and ICU length of stay 1.
Pain Management: Specific Drug Regimens
First-Line Opioid Selection
Fentanyl is the preferred initial opioid for most ICU patients due to rapid onset and easy titration 2:
- Bolus dose: 25-100 mcg IV every 5-15 minutes as needed
- Continuous infusion: Start at 25-50 mcg/hour, titrate by 25 mcg/hour increments
- Critical caveat: Highly lipophilic with large volume of distribution—prolonged infusions (>48-72 hours) cause significantly prolonged half-life and delayed emergence 2
Hydromorphone for patients requiring longer-acting analgesia 2:
- Bolus dose: 0.2-0.6 mg IV every 1-2 hours as needed
- Continuous infusion: 0.5-3 mg/hour
- Advantage: No active metabolites, quick onset, suitable for renal dysfunction
Morphine when cost is a concern but use cautiously 2:
- Bolus dose: 2-5 mg IV every 2-4 hours
- Continuous infusion: 2-10 mg/hour
- Critical warning: Active metabolite (morphine-6-glucuronide) accumulates in renal failure causing prolonged sedation and respiratory depression 2, 3
- Avoid in: Renal impairment, hemodynamic instability (histamine release) 2
Remifentanil for patients requiring predictable, rapid offset 2, 4:
- Continuous infusion: 0.1-0.4 mcg/kg/min (6-24 mcg/min for 70kg patient)
- Advantage: Organ-independent metabolism via plasma esterases, context-sensitive half-time remains short regardless of infusion duration 4
- Critical warning: Risk of glycine toxicity in renal dysfunction; hyperalgesia with abrupt discontinuation—must taper 2, 4
Multimodal Analgesia: Opioid-Sparing Adjuncts
Acetaminophen (First-Line Adjunct)
- Dose: 1000 mg IV every 6 hours (maximum 4 g/day) 2
- Renal/hepatic dysfunction: Safe in renal failure; reduce dose to 2-3 g/day maximum in hepatic impairment
- Warning: Risk of hypotension in hemodynamically unstable patients with IV formulation 2
Gabapentin/Pregabalin (For Neuropathic Pain)
- Gabapentin: 100-300 mg PO/NG three times daily, titrate to 900-3600 mg/day divided TID
- Pregabalin: 75 mg PO/NG twice daily, titrate to 150-300 mg twice daily
- Critical warning: Life-threatening accumulation and toxicity in renal impairment—reduce dose by 50-75% if CrCl <60 mL/min 2
- Strong recommendation for neuropathic pain 2
Ketamine (Post-Surgical Patients)
- Low-dose infusion: 0.05-0.2 mg/kg/hour (3.5-14 mg/hour for 70kg patient)
- Use specifically in: Post-surgical ICU patients at high risk of opioid side effects 2
- Hepatic/renal dysfunction: Hepatically metabolized; reduce dose by 25-50% in severe hepatic impairment
AVOID These Adjuncts
- NSAIDs (COX-1 selective): Do NOT use routinely—significant bleeding risk, renal toxicity, cardiovascular events 2
- IV Lidocaine: Do NOT use routinely—insufficient evidence, risk of toxicity 2
Sedation Management: Specific Drug Regimens
Light Sedation Target (RASS -2 to 0)
Target sedation level: Patient is lightly sedated, easily arousable, able to follow commands (Richmond Agitation-Sedation Scale [RASS] -2 to 0) to reduce ventilator time, ICU length of stay, and mortality 1, 2.
Propofol (Preferred for Short-Term Sedation <48-72 Hours)
Initial infusion: 5 mcg/kg/min (0.3 mg/kg/hour) 5:
- Increase by 5-10 mcg/kg/min (0.3-0.6 mg/kg/hour) every 5 minutes until target sedation achieved
- Maintenance range: 5-50 mcg/kg/min (0.3-3 mg/kg/hour) for most patients 5
- Maximum dose: Do NOT exceed 4 mg/kg/hour (67 mcg/kg/min) unless benefits clearly outweigh risks 5
Renal dysfunction: No dose adjustment needed—propofol pharmacokinetics unchanged 5
Hepatic dysfunction: No dose adjustment needed for mild-moderate impairment; reduce by 20-30% in severe cirrhosis 5
Elderly/debilitated patients: Reduce initial and maintenance doses to 80% of usual adult dosing 5
Critical warnings:
- Propofol infusion syndrome risk with prolonged use (>48 hours) at high doses (>4 mg/kg/hour)—monitor triglycerides, lactate, creatine kinase 5
- Causes hypotension—use cautiously in hemodynamically unstable patients 5
- Contains lipid vehicle—count as caloric intake (1.1 kcal/mL) 5
Dexmedetomidine (Preferred for Longer-Term Sedation, Delirium Prevention)
Loading dose: 1 mcg/kg IV over 10 minutes (optional—omit if hypotension risk)
Maintenance infusion: 0.2-0.7 mcg/kg/hour 1:
- Start at 0.2-0.4 mcg/kg/hour
- Titrate by 0.1 mcg/kg/hour every 30 minutes to target sedation
- Maximum: 1.5 mcg/kg/hour (though doses >0.7 mcg/kg/hour increase adverse effects)
Renal dysfunction: No dose adjustment needed—minimal renal elimination
Hepatic dysfunction: Reduce dose by 25-50% in moderate-severe hepatic impairment (Child-Pugh B-C)
Advantages over benzodiazepines: Reduces delirium duration by ~20%, allows easier arousal, preserves respiratory drive 1, 2, 6
Critical warnings:
- Bradycardia and hypotension common—avoid loading dose in hemodynamically unstable patients 1
- Less effective for deep sedation—combine with low-dose propofol if needed
AVOID Benzodiazepines
Strong recommendation against routine benzodiazepine use due to increased delirium, prolonged mechanical ventilation, and worse outcomes 1, 2:
- Use ONLY for alcohol/benzodiazepine withdrawal, seizures, or refractory agitation
- If required: Lorazepam 1-4 mg IV every 2-6 hours (intermittent dosing preferred over infusion)
Protocol-Based Management Algorithm
Step 1: Assess and Treat Pain FIRST
- Use validated pain scale (CPOT or BPS for nonverbal patients)
- Administer opioid (fentanyl preferred) to achieve pain score <3/10
- Add acetaminophen 1g IV q6h routinely 2
Step 2: Add Sedation ONLY If Needed After Adequate Analgesia
- Assess sedation need using RASS scale
- Target RASS -2 to 0 (light sedation) 1, 2
- Choose sedative based on duration:
- <48-72 hours: Propofol 5-50 mcg/kg/min
- >72 hours or delirium risk: Dexmedetomidine 0.2-0.7 mcg/kg/hour
Step 3: Daily Sedation Assessment
- Perform daily sedation interruption or lightening 1
- Reassess pain and sedation every 4 hours minimum using validated scales 1, 2
- Titrate downward to minimum effective dose 1, 2
Step 4: Procedural Pain Management
- Administer opioid bolus 15-30 minutes before painful procedures 1
- Fentanyl: 50-100 mcg IV 5-10 minutes before procedure
- Remifentanil: Increase infusion by 0.05-0.1 mcg/kg/min during procedure 4
Critical Organ Dysfunction Adjustments
Renal Impairment (CrCl <30 mL/min)
- Avoid: Morphine (active metabolite accumulation) 2, 3
- Preferred opioids: Fentanyl, hydromorphone, remifentanil 2
- Reduce gabapentin/pregabalin by 50-75% 2
- Propofol: No adjustment needed 5
- Dexmedetomidine: No adjustment needed
Hepatic Impairment (Child-Pugh B-C)
- Reduce propofol by 20-30% in severe cirrhosis 5
- Reduce dexmedetomidine by 25-50%
- Reduce acetaminophen to 2-3 g/day maximum 2
- Reduce ketamine by 25-50%
- Opioids: All require dose reduction by 25-50% due to decreased metabolism
Combined Renal-Hepatic Dysfunction
- Preferred regimen: Remifentanil (organ-independent metabolism) + low-dose propofol 2, 4
- Start all agents at 50% of usual dose, titrate slowly
- Monitor closely for accumulation and prolonged effects
Common Pitfalls to Avoid
Never administer sedatives before adequately treating pain—this fundamental error persists despite clear evidence and directly worsens outcomes 2, 6:
- Always assess pain first using validated scales
- Achieve pain control before considering sedation
Avoid deep sedation practices that became common during COVID-19 pandemic—these directly harm patients by increasing delirium, prolonged ventilation, and mortality 1, 6:
- Target RASS -2 to 0, not RASS -4 to -5
- Resist pressure to "keep patient comfortable" with deep sedation
Do not use continuous benzodiazepine infusions except for specific indications (withdrawal, seizures)—associated with 20% increase in delirium 1, 2, 6
Avoid propofol >4 mg/kg/hour or >48-72 hours without compelling indication—risk of propofol infusion syndrome 5
Do not forget to reduce opioid doses when adding multimodal agents—acetaminophen and gabapentin allow 20-40% opioid dose reduction 2
Monitor for drug accumulation in organ dysfunction—morphine metabolites in renal failure, propofol in severe hepatic failure, gabapentin in any renal impairment 2, 5, 3