Propofol it's rare complications

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Propofol it's rare complications

• Department of Anesthesiology and Pain Medicine,
• School of Medicine, Kyung Hee University
• Park, Sung Wook

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Propofol Infusion Syndrome
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Propofol Infusion Syndrome

• A rare and lethal syndrome described in
  critically ill patients undergoing long-term
  propofol infusion at high doses
• Main features
• Cardiac failure, rhabdomyolysis, severe metabolic
  acidosis, renal failure

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Propofol Infusion Syndrome

• Priming factors
• CNS activation with production of catecholamines
  and glucocorticoids
• Systemic inflammation with cytokine production
• Triggering factors
• High-dose long-term propofol infusion
• (gt 4-5 mg/kg/hr, gt 48 hr)
• Supportive treatments with catecholamines and
  corticosteroids

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Propofol Infusion Syndrome

• Cardiac and peripheral muscle injury
• Plasma CK ?
• Troponin I ?
• Myoglobinuria
• Histologic Findings
• Severe myocytolysis in the skeletal muscle and
  myocardium

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Propofol Infusion Syndrome

• Propofol
• Cardiac and peripheral m. injury
• Direct inhibitory effects of propofol
• Propofol-mediated impaired fatty acid oxidation
• Catecholamines
• Cardiac and peripheral m. injury
• The catecholamine-propofol vicious circle
• Direct myocytolytic effects of catecholamines

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Propofol Infusion Syndrome

• Direct inhibitory effects of propofol
• Muscle cytochrome oxidase deficiency
• Mitochondrial respiratory-chain enzyme deficiency
• Propofol-mediated impaired fatty acid oxidation
• Free fatty acids (FFA)
• Derive from catecholamine-mediated lipolysis of
  adipose tissues
• Most important fuel for myocardium skeletal
  muscle
• Propofol-induced blockade of mitochondrial fatty
  oxidation
• (inhibition of carnitine palmitoyl
  transferase 1)
• ? Imbalance between energy demand and supply
• ? Cardiac and peripheral muscle necrosis
• Accumulation of unutilised FFA
• Pro-arrhythmogenic properties

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Propofol Infusion Syndrome

• The catecholamine-propofol vicious circle
• Catecholamines ?
• ? Cardiac output ?
• ? First-pass dilution? Clearance of propofol
  ?
• ? Propofol blood concentration ?
• ? Reversal of anesthesia
• ? Propofol infusion rates ?
• ? Negative inotropic effect of propofol
• ? Catecholamine requirements ?
• Progressive myocardial depressive effect

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Propofol Infusion Syndrome

• Direct myocytolytic effects of catecholamines
• Myofibrillar degeneration (MD)
• contraction band necrosis coagulative
  myocytolysis
• Response of myocardial tissue to severe injuries
• m. fiber excessively contracted state with
  contraction bands

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Propofol Infusion Syndrome

• Steroids
• Peripheral m. injury
• Proteolysis due to activation of the
  ubiquitin-proteasome system

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Propofol Infusion Syndrome

• SIRS MODS
• Cardiac and peripheral m. injury
• An exaggerated pro-inflammatory cytokine response
  
• Or an inadequate anti-inflammatory cytokine
  response
• Cardiac cell injury in sepsis septic shock
• Critical illness polyneuropathy myopathy

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Propofol Infusion Syndrome

• CNS stimulation
• subarachnoid hemorrhage, severe head trauma,
  status epilepticus, encephalitis, meningitis,
  stroke
• Acute neurological illnesses with excessive
  stress response
• Impaired immune responses
• Increased susceptibility
• to severe infection
• Cardiac and peripheral
• muscle damage
• can be boosted

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• Pro-inflammatory cytokines produced at the site
  of tissue damage activate the stress system,
  causing glucocorticoid and catecholamine
  secretion.
• Stress response usually has an anti-inflammatory
  and immunosuppressive effect. If this is
  inadequate, susceptibility to inflammatory
  diseases is enhanced.
• The persistent pro-inflammatory state with
  hypercatabolism causes progressive organ
  dysfunction, including cardiac and skeletal
  muscle dysfunction.
• With the body so primed, high doses of drugs like
  propofol, glucocorticoids and catecholamines may
  trigger the syndrome of cardiac failure and
  rhabdomyolysis, followed by metabolic acidosis
  and acute renal failure (FFA plasmatic free fatty
  acids)

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Propofol Infusion Syndrome

• Avoid high dose propofol (gt4-5 mg/kg/hr) for
  prolonged periods (gt48 hr)
• Critically ill neurological patients
• Subarachnoid hemorrhage, status epilepticus,
  meningitis, encephalitis, stroke
• Patients with severe burns, trauma, severe
  infections, pancreatitis, acute exacerbation of
  asthma
• Alternatives
• Lorazepam (0.010.1mg/kg/hr)
• Midazolam (0.040.2mg/kg/hr)

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Abuse Dependence
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Abuse Dependence

• Molecular targets of propofol
• GABAA receptor
• Direct activation potentiation
• NMDA receptor
• Inhibit phosphorylation
• Hallucinations
• Fatty acid amide hydrolase (FAAH)
• Competitive inhibition of endocannabinoid
  anandamide degradation
• Sedative-hypnotic properties
• Potential of abuse

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Abuse Dependence

• Mesocorticolimbic dopaminergic circuit
• All drugs of abuse enhance the activity of the
  ciruit
• Quanti?ed by assessing extracellular dopamine
  concentration in the nucleus accumbens
• Dopamine measurements in the nucleus accumbens
  after nonanesthetic and anesthetic doses of
  propofol in rats. (Anesth Analg.
  200295915919.)
• Increases of dopamine concentration for
  subanesthetic and anesthetic doses

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Abuse Dependence

• Rewarding effects of propofol
• Propofol at subanaesthetic doses may have abuse
  potential in healthy volunteers. (Anesth Analg.
  1993 77 544552.)
• Propofol vs Soy-based lipid emulsion
• 50 of volunteers -gt propofol
• Pleasant subjective effects
• Recreational use of propofol (?)

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Abuse Dependence

• Subjective effects of propofol
• The mood-altering effects of subanaesthetic doses
  of propofol
• Feeling high, light-headed, spaced out, sedated
• Dream incidence rate during propofol anesthesia
  (20-60)
• Described as pleasant, related to sex
• Recovery of propofol anesthesia
• Euphoria, sexual hallucinations, disinhibition

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Abuse Dependence

• Human case reports
• 10 cases (1992-2008)
• 8 cases Healthcare professional
• 4 cases Death
• Propofol withdrawal with medical assistance
• 3 cases All cases relapse
• Propofol dependence
• Psychological dependence
• No physical signs of dependence
• Not in patients receiving propofol for anesthesia
  or sedation

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Abuse Dependence

• Propofol abuse can cause death
• Respiratory depression
• The rapidity of the injection without ventilatory
  assistance by inducing apnea
• Pulmonary edema
• Hypotension

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Postoperative Pancreatitis
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Postoperative Pancreatitis

• 12 cases (1985-2005)
• Mechanism
• Unclear
• Prolonged propofol infusion (usually after 72h)
• Increase triglyceride levels
• Increase in pancreatic lipase in pancreatic
  capillaries
• In?ammatory process
• Observed after single dose of propofol without
  prior hyperlipidemia