Adverse Drug Reactions

ADR Basics - Danger Decoder

• Definition: Harmful, unintended reaction to a drug at normal therapeutic doses.
• Classification (Rawlins & Thompson):
  • Type A (Augmented):
    • Pharmacologically predictable, dose-dependent.
    • Common (≈80% of ADRs). Low mortality.
    • Manage: Reduce dose or withhold.
    • E.g., Bleeding with anticoagulants; respiratory depression with opioids.
  • Type B (Bizarre/Idiosyncratic):
    • Non-dose-related, unpredictable; patient-dependent (genetic/immunologic).
    • Uncommon. Higher mortality.
    • Manage: Withdraw drug immediately; avoid in future.
    • E.g., Anaphylaxis to penicillin; Malignant Hyperthermia with succinylcholine.
• 📌 Mnemonic: A = Augmented (dose-related); B = Bizarre (patient-related).
• Severity: Graded: Mild, Moderate, Severe, Lethal.
• Causality Assessment: Naranjo Algorithm commonly used.

⭐ Type B reactions, though rare, often have higher morbidity and mortality, making their recognition critical an anesthesiology practice for drugs like succinylcholine or antibiotics administered perioperatively.

Drug Dossiers - Anesthetic Antagonists

• Naloxone (Opioid Antagonist)

  • Mech: Competitive antagonist at $\mu, \kappa, \delta$ receptors.
  • Uses: Opioid OD, respiratory depression reversal.
  • Dose: 0.4-2 mg IV; Peds: 0.01 mg/kg. Repeat prn.
  • Onset: 1-2 min (IV). Duration: 30-90 min (⚠️ shorter than agonist).
  • ADRs: Acute withdrawal, pulmonary edema.
  • 📌 "NAloxone = Narcotic Antagonist."

• Flumazenil (Benzodiazepine Antagonist)

  • Mech: Competitive antagonist at GABA-A BZD site.
  • Uses: BZD OD, sedation reversal.
  • Dose: Initial 0.2 mg IV, then 0.1 mg q1min up to 1 mg. Peds: 0.01 mg/kg.
  • Onset: 1-2 min. Duration: 30-60 min (⚠️ shorter than agonist).
  • ADRs: Seizures (esp. BZD dependence/TCA OD), agitation.
  • Contra: Seizure disorder, BZD dependence, TCA OD.

  ⭐ Flumazenil may precipitate seizures in chronic BZD users or with pro-convulsant co-ingestion (e.g., TCAs).

• Sugammadex (NMBA Antagonist: Rocuronium, Vecuronium)

  • Mech: Selective relaxant binding agent; encapsulates steroidal NMBAs.
  • Uses: Reversal of rocuronium/vecuronium blockade.
  • Dose: Mod (TOF 2): 2 mg/kg; Deep (PTC 1-2): 4 mg/kg; Immed (Roc 1.2 mg/kg): 16 mg/kg IV.
  • Onset: <3 min for TOF >0.9.
  • ADRs: Anaphylaxis, bradycardia. ⚠️ ↓ hormonal contraceptive efficacy (7 days alt.).
  • 📌 "SUGAmmadex = SUcks GAmmacyclodextrin."

Crisis Calls - Code Red Reactions

Immediate recognition and management are critical for these life-threatening anesthetic adverse drug reactions.

• Anaphylaxis

  • Triggers: Antibiotics (penicillin), muscle relaxants (suxamethonium, rocuronium), latex, colloids.
  • Signs: Rapid onset hypotension, bronchospasm, flushing, urticaria, angioedema.
  • Management:
    • STOP agent. ABCs (airway, 100% O2, IV fluids).
    • Epinephrine: 0.3-0.5 mg IM (1:1000) or 50-100 mcg IV (1:10000) for severe cases. Repeat q5-15min.
    • Antihistamines (H1/H2), Corticosteroids (Hydrocortisone 100-200 mg IV).

• Malignant Hyperthermia (MH)

  • Triggers: Volatile anesthetics (sevoflurane), Suxamethonium.
  • Signs: ↑ETCO2 (early, persistent), tachycardia, muscle rigidity (masseter), hyperthermia (late), acidosis.

  ⭐ Unexplained, persistent rise in End-Tidal CO2 (ETCO2) is often the earliest and most sensitive sign of Malignant Hyperthermia.

  • Management:
    • STOP triggers. Call help. Hyperventilate (100% O2, high flows).
    • Dantrolene: 2.5 mg/kg IV push, repeat q5-10min (max 10 mg/kg).
    • Active cooling. Treat acidosis, hyperkalemia.

• Local Anesthetic Systemic Toxicity (LAST)

  • Causes: Accidental IV injection, excessive dose, rapid absorption.
  • Signs: CNS (metallic taste, tinnitus, agitation, seizures, coma), CVS (arrhythmias, hypotension, cardiac arrest).
  • Management:
    • STOP LA. ABCs. Seizure control (benzodiazepines).
    • Lipid Emulsion (20% Intralipid): Bolus 1.5 mL/kg, infusion 0.25 mL/kg/min. Max 12 mL/kg.
    • Modified ACLS (epinephrine < 1 mcg/kg; amiodarone for VT/VF).

High‑Yield Points - ⚡ Biggest Takeaways

• Malignant Hyperthermia: Triggered by succinylcholine & volatile anesthetics; RYR1 gene implicated; treat with dantrolene.
• Anaphylaxis: Common with NMBs (rocuronium), antibiotics, latex; IgE-mediated; adrenaline is cornerstone treatment.
• Suxamethonium Apnea: Due to pseudocholinesterase deficiency (genetic/acquired); causes prolonged muscle paralysis.
• Propofol Infusion Syndrome (PRIS): With prolonged, high-dose propofol; features metabolic acidosis, rhabdomyolysis, cardiac failure.
• Local Anesthetic Systemic Toxicity (LAST): CNS symptoms (seizures) precede cardiac toxicity; lipid emulsion therapy is crucial.
• Opioid-induced Chest Wall Rigidity: Especially with rapid, high-dose fentanyl; manage with naloxone or NMBs.