Midazolam

Keyword

Midazolam

Physicochemicals

• Lipid soluble (생리적 pH에서), midazolam은 BDZ중에서도 가장 lipid soluble.
• pH dependent한 용해도깨문에 pH 3.5의 buffered acidic medium에서 수용성이 됨.
• 지용성으로 인해 빠른 CNS효과와 Relatively large volumes of distribution이 나타남.

Pharmacokinetics

• Shot-acting
  • 분포 반감기 : 6~15 min
  • 제거 반감기 1.7~3.5 Hr
  • Clearance : 5.8~9.0 mL/kg/min (hepatic blood flow에 영향받음)
  • Vd : 1.1~1.7 L/Kg
• Affecting factors : age, gender, race, hepatic and renal disease, obesity

Effects

• CNS
  • hypnotic, sedative, anxiolytic, amnestic, anticonvulsant
  • centrally produced muscle-relaxing properties
• Respiratory system
  • dose-related central respiratory system depression
  • Increase incidence Old age, debilitating disease, and other respiratory depressant drugs
• Cardiovascular
  • Homeostatic reflex들이 보존 (baroreflex 제외) 되어 혈역학적으로 안정.
  • 전신혈관 감소로 aBP 중등도로 감소시킴
  • Heart rate, ventricular filling pressures, CO 유지
  • Intubation, 수술등에 의한 stress는 block시키지 못함.

Dosage

• Premedication : anxiolysis, sedation, amnesia, vagolysis, sympatholysis, reduction of PONV
  • Adult : 7.5 to 15 mg PO
  • Ped : 0.25 mg/kg (Max 20mg)
• Sedation : 불안 완화, 수술/시술중의 불편한 기억 제거
  • 적절한 sedation, dysarthria가 있을 때까지 titration필요
  • 2~3분에 peak effect
  • 0.5~1mg IV 반복 투여,
  • 0.07 mg/kg IM
• Anesthesia Induction & maintenance
  • 0.1 ~ 0.2 mg/kg (premedicated Pt), ~ 0.3 mg/kg (unpremedicated Pt)
  • 30 ~ 60 초 내에 효과 나타나며 2~3분에 혈장 평형농도와 EEG에 효과 나타냄
  • 흡입마취제 or Opioids병용시
    • Initial dose 0.05 ~ 0.15 mg/kg bolus and continuous infusion 0.25 ~ 1 μg/kg/minute
  • Repeated bolus administrations or with continuous infusion시 혈액 내 축적됨.

Complications

• Undesirable degree or prolonged interval of postoperative amnesia, sedation
• Rarely, respiratory depression
• Flumazenil로 reverse될 수 있음.

Reference

Miller’s Anesthesia, 8th Ed. Ch30, p 837-843