What are the common ICU drugs, their dosages, titrating methods, and indications for managing hypotension, sedation, analgesia, and infection?

ICU Drugs: Dosages, Titration Methods, and Indications

Analgesia (Pain Management)

Intravenous opioids are the first-line agents for non-neuropathic pain in ICU patients, with all opioids equally effective when titrated to similar pain endpoints. 1

Opioid Selection and Dosing

• Morphine: 1-5 mg IV bolus (0.1-0.15 mg/kg) or 2-15 mg/hr continuous infusion 2

  • Monitor for histamine release causing hypotension and vasodilation 2
  • Active metabolites accumulate in renal failure, requiring dose reduction 2

• Fentanyl: Preferred in hemodynamically unstable patients due to minimal histamine release 2

  • Rapid onset and offset make it suitable for procedural pain 1

• Pethidine (Meperidine): 10 mg bolus or 10-20 mg/hr continuous infusion 2

  • Less potent than morphine 2

Adjunctive Analgesics

• Ketamine: Sub-anesthetic doses administered with opioids to reduce overall opioid requirements 1

  • Acts as NMDA antagonist, particularly useful for opioid-refractory pain 1
  • Risk of psychotomimetic effects (dysphoria, nightmares, hallucinations) at higher doses 1

• Acetaminophen IV: Safe and effective adjunct to opioids, reduces opioid-related side effects 1

• Neuropathic pain: Add gabapentin or carbamazepine to IV opioids 1

Critical Pain Management Principles

• Never withhold analgesia to maintain blood pressure or stimulate respiratory effort 1
• Premedicate for all procedures, including rapid ones like chest tube removal 1
• Prescribe bowel regimen (senna or lactulose) with sustained opioid dosing unless contraindicated 1

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Sedation

Non-benzodiazepine sedatives (propofol or dexmedetomidine) should be used preferentially over benzodiazepines, and light sedation should be targeted rather than deep sedation. 1, 3

First-Line Sedatives

Propofol

• Loading: 5 μg/kg/min over 5 minutes (only if hypotension unlikely) 1, 4
• Maintenance: 5-50 μg/kg/min 1, 4
• Onset: 1-2 minutes; Half-life: 3-12 hours (short-term use) 1
• Titration: Start ICU sedation at 5 μg/kg/min, increase by 5-10 μg/kg/min increments every 5 minutes minimum until desired sedation achieved 4
• Maximum: Do not exceed 4 mg/kg/hr unless benefits outweigh risks 4
• Adverse effects: Hypotension, respiratory depression, propofol infusion syndrome, hypertriglyceridemia, pancreatitis 1
• Advantages: Rapid onset/offset allows daily sedation interruption and neurological assessments 3

Dexmedetomidine

• Loading: 1 μg/kg over 10 minutes (avoid in hemodynamically unstable patients) 1
• Maintenance: 0.2-0.7 μg/kg/hr (may increase to 1.5 μg/kg/hr as tolerated) 1
• Onset: 5-10 minutes; Half-life: 1.8-3.1 hours 1
• Adverse effects: Bradycardia, hypotension; hypertension with loading dose 1
• Advantages: Reduced delirium incidence, improved patient communication compared to benzodiazepines 3

Second-Line Sedatives (Benzodiazepines)

Midazolam

• Loading: 0.01-0.05 mg/kg over several minutes 1
• Maintenance: 0.02-0.1 mg/kg/hr 1
• Onset: 2-5 minutes; Half-life: 3-11 hours 1
• Use: Short-term sedation only 1
• Adverse effects: Respiratory depression, hypotension, increased delirium risk 1

Lorazepam

• Loading: 0.02-0.04 mg/kg (≤2 mg) 1
• Maintenance: 0.02-0.06 mg/kg q2-6hr PRN or 0.01-0.1 mg/kg/hr (≤10 mg/hr) 1
• Onset: 15-20 minutes; Half-life: 8-15 hours 1
• Adverse effects: Propylene glycol-related acidosis and nephrotoxicity with prolonged infusion 1

Sedation Management Protocol

• Target light sedation (patient arousable, follows simple commands) rather than deep sedation 1
• Use validated sedation scales (RASS or SAS) to titrate sedation 1
• Implement daily sedation interruption to assess neurologic status 3
• Attempt non-pharmacologic approaches (adequate analgesia, reorientation, sleep optimization) before sedatives 1
• Avoid abrupt discontinuation; taper gradually to prevent anxiety and agitation 4

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Vasopressors (Hypotension Management)

Norepinephrine is the first-line vasopressor for septic shock, targeting a MAP ≥65 mmHg, with vasopressin added as second-line therapy if target MAP cannot be achieved. 5, 6

First-Line: Norepinephrine

• Target MAP: ≥65 mmHg in most patients 5, 6
• Administration: Requires central venous access; never administer peripherally due to tissue necrosis risk 5
• Titration: Increase dose by 25-50% immediately before anesthesia induction to counteract vasodilation 5
• Monitoring: Establish continuous arterial blood pressure monitoring before initiation 5, 6
• Advantages: Superior efficacy and safety compared to other agents 6, 7

Second-Line: Vasopressin

• Indication: Add when maximum norepinephrine doses fail to achieve target MAP 5, 6
• Dose: 0.01-0.03 units/minute (up to 0.03 U/min maximum) 5, 6
• Mechanism: Acts on different vascular receptors, has norepinephrine-sparing effects 5
• Caution: Should not be used as initial single vasopressor 6
• Evidence: No mortality difference vs. norepinephrine alone in septic shock, but may benefit less severe cases 8

Third-Line: Epinephrine

• Indication: Add if MAP remains <65 mmHg despite norepinephrine plus vasopressin 5
• Dose: 0.1-0.5 mcg/kg/min 5
• Adverse effects: Hyperglycemia, hyperlactatemia, acidosis, hypokalemia 7

Agents to Avoid

• Dopamine: Associated with higher mortality and more arrhythmias compared to norepinephrine 5, 6

  • Only use as alternative in highly selected patients with low arrhythmia risk or bradycardia 6
  • Never use low-dose dopamine for "renal protection" 5, 6

• Phenylephrine: Avoid except as salvage therapy; may raise blood pressure while worsening tissue perfusion through excessive vasoconstriction without cardiac output support 5

Vasopressor Management Protocol

• Administer at least 30 mL/kg crystalloid before or concurrent with vasopressor initiation 5
• Monitor perfusion markers beyond MAP: lactate, urine output, mental status 5
• Consider higher MAP target (80-85 mmHg) in chronic hypertension, though this increases arrhythmia risk 6
• Use dynamic variables (pulse pressure variation, stroke volume variation) to guide fluid therapy 6
• Add dobutamine 5-20 mcg/kg/min if myocardial dysfunction evident in refractory shock 5

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Special Considerations

Elderly, Debilitated, or ASA-PS III/IV Patients

• Reduce propofol and benzodiazepine doses to approximately 80% of usual adult dosage 4
• Avoid rapid bolus administration 1, 4
• Increased sensitivity to sedative effects and exaggerated hemodynamic responses 1

Renal Dysfunction

• Active metabolites of midazolam and diazepam accumulate, prolonging sedation 1
• Lorazepam elimination half-life increases 1
• Morphine metabolites accumulate, requiring dose adjustment 2

Hepatic Dysfunction

• Benzodiazepine clearance reduced 1
• Propofol dosage reduction required 4

Critical Pitfalls

• Never mix norepinephrine with sodium bicarbonate or alkaline solutions (inactivates drug) 5
• Monitor for propofol infusion syndrome with high-dose or prolonged infusions 3
• Benzodiazepines are strong independent risk factors for delirium 3
• Oversedation causes respiratory depression, hypotension, prolonged mechanical ventilation 2