MORPHINE 

 MECHANISM OF ACTION

 Receptor Activity

• μ (mu) receptor agonist (primary)
• Also weak activity at:
  • κ (kappa)
  • δ (delta)

 Effects via μ-receptor

• Analgesia (supraspinal + spinal)
• Respiratory depression
• Euphoria / sedation
• Reduced sympathetic tone

 Cellular Mechanism

• Opens K⁺ channels → hyperpolarization
• Closes Ca²⁺ channels → ↓ neurotransmitter release
• ↓ Substance P, glutamate transmission

PHARMACOKINETICS 

• Accumulation in renal failure → prolonged sedation + toxicity

 DOSE IN CRITICAL CARE

 IV Bolus

• 2–5 mg IV slow push
• Repeat every 5–10 min (titration)

 Infusion

• 0.05–0.1 mg/kg/hr

 Special Situations

• Elderly / renal failure → reduce dose
• Opioid-naïve → start low

 INDICATIONS IN ICU

 1. Analgesia (Primary Use)

• Trauma
• Postoperative pain
• Cancer pain
• Burns

 2. Acute Pulmonary Edema

• Reduces:
  • Preload (venodilation)
  • Anxiety
• Improves dyspnea

 3. Acute Coronary Syndrome (ACS)

• Pain relief
• ↓ Sympathetic drive

 Recent guidelines: use cautiously (possible worse outcomes due to delayed antiplatelet absorption)

 4. Dyspnea in ICU

• End-stage COPD
• Palliative care

 HEMODYNAMIC EFFECTS

 ICU Warning

• Avoid in shock / unstable patients

 ADVERSE EFFECTS

 Common

• Respiratory depression
• Nausea, vomiting
• Constipation
• Urinary retention

 Serious

• Hypotension
• Histamine release → bronchospasm
• Delirium (ICU patients)

 CONTRAINDICATIONS

• Severe respiratory depression
• Acute bronchial asthma
• Paralytic ileus
• Raised ICP (relative)

 SPECIAL ICU SITUATIONS

 Raised ICP

• ↑ PaCO₂ → cerebral vasodilation → ↑ ICP
  ➡️ Use cautiously

 ARDS / Ventilated Patients

• May be used but:
  • Prefer fentanyl (less histamine release)

 Renal Failure

• Avoid or reduce dose
• Metabolite accumulation → toxicity

COMPARISON WITH OTHER OPIOIDS 

 ICU Preference: Fentanyl > Morphine

REVERSAL

 Antidote

Naloxone

• Dose: 0.04–0.4 mg IV
• Repeat as needed