propofol (Diprivan)

Introduction

Tradename: Diprivan.

Indications

• induction or maintenance of anesthesia
• short-term sedation (24 hours or less) for intubated intensive care patients

Contraindications

• when general anesthesia is contraindicated
• NOT for obstetrical anesthesia
• NOT for neurosurgical anesthesia

pregnancy category = b

safety in lactation = -

Dosage

• 40 mg IV every 10 sec until induction
• 2-2.5 mg/kg IV drip
• initial bolus dose of 0.5-1.0 mg/kg for adults or 1.5-2.0 mg/kg for children
  • titrate every 1-3 minutes to effect with boluses of 0.25-0.5mg/kg (adults) or 0.5-1.0 mg/kg (children)
  • infusions may avoid the "peak & trough" effect of boluses
  • use 100-150 ug/kg/min (adults) & up to 250 ug/kg/min (children)

* one provider should be dedicated to administering propofol, monitoring vital signs (cardiac monitoring, pulse oximetry, capnography, & blood pressure & respiratory rate every 5 minutes), & performing any needed resuscitation

* optimize volume status prior to propofol administration to avoid hypotension

* propofol provides sedation & amnesia without analgesia; thus coadminister ketamine, fentanyl, or a local anesthetic

Injection: 10 mg/mL (20 mL)

Pharmacokinetics

• rapid onset of action (within 30 seconds of IV bolus)
• 3 compartment model describes disposition & elimination
  • plasma
  • rapidly equilibrating compartment
  • slowly equilibrating compartment
• equilibration dependent upon rate & duration of infusion
  • long infusions result in tissue accumulation & increased time awakening when the drug is stopped
• metabolized by liver; conjugation to inactive metabolites
• eliminated by the kidney
• duration of action 3-10 minutes (variable)
• terminal 1/2life for a 10 day infusion is 1-3 days

elimination via liver

Adverse effects

• common (> 10%)
  • nausea
• less common (1-10%)
  • fever, hypotension, bradycardia, apnea, vomiting, abdominal cramping, cough, flushing
• uncommon (< 1%)
  • chest pain, dry mouth, somnolence, tachycardia, syncope, agitation, bronchospasm, diarrhea, ear pain, pruritus, dyspnea, tremor, confusion, twitching
• propofol-associated infusion syndrome (rare)
  • lactic acidosis
  • rhabdomyolysis
  • hypertriglyceridemia
  • J point elevation on electrocardiogram
  • occurs at doses >4 mg/kg/hour for > 48 hours
• other
  • decreased systemic vascular resistance
  • anaphylactic reactions
  • withdrawal symptoms with longer infusions
  • contamination & risk of secondary infection*
  • immune suppression
  • tolerance
  • delayed seizures
  • green urine
  • arrhythmias
• patients < 6 months of age & > 75 years of age have higher rates of complications

* Tubing must be changed every 12 hours to decrease risk of bacterial contamination

Drug interactions

• CNS depressants
• cardio-respiratory depressants

Laboratory

• propofol in serum/plasma
• propofol glucuronide in urine
• urine appearance: may be green

Mechanism of action

• IV sedative hypnotic
• sedative general anesthetic
• diisopropylphenol in a lipid emulsion
• NOT an analgesic
• 1.1 kcal of fat/mL (1 g of fat/10 mL)

More general terms

• general anesthetic injectable

Additional terms

• fospropofol (Lusedra, Aquavan)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4943