Propofol Infusion Syndrome in Children

Propofol Infusion Syndrome in ChildrenKeeping children calm and cooperative is part of our job and often leads us to using fancy medicines like Ketamine and Nitrous Oxide. Of course, it is important to have a patient safely sedated during a minor procedure like Lumbar Puncture, Facial Laceration Repair, or Incision and Drainage; however, it is even more imperative having just intubating a child. Aside from Ketamine (my favorite drug – professionally speaking), Propofol is one of the most often used tools to keep patients sedated, but our use of it in the ED can occasionally lead to some consternation amongst our friends in the PICU. The reason: concern for mortality! Let us take a minute to digest a Morsel on this important consideration- Propofol Infusion Syndrome:

 

Propofol Basics

  • First developed in 1973 (not THAT long ago) in the United Kingdom
  • Chemically described as 2,6-diisopopylphenol. [Chidambaran, 2015]
    • Insoluble in water; must be in oil-in-water emulsion
    • Has pKa of 11.
  • Propofol works via activation of central GABA pathways and inhibition of NMDA pathways. [Chidambaran, 2015; Diedrich, 2011]
  • Propofol Efficacy and Usage:
    • Propofol exhibits many pharmacologic advantages:
      • Rapid onset
      • Short duration
      • Few side effects (especially post-anesthetic nausea)
    • It is also known to be safe and effectively when administered for procedural sedations inside and outside of the OR. [Kang, 2018; Chidambaran, 2015; Chiaretti, 2014; Rajasekaran, 2014; Vespasiano, 2007; Wheeler, 2003]
      • Used for IV induction and Maintenance for General Anesthesia in children. [Kang, 2018]
        • FDA approves its use for:
          • Maintenance of anesthesia in children 2 months of age and older.
          • Induction of anesthesia for children 3 years of age and older.
        • Obviously, it is used “off label” beyond these situations.
      • Commonly used for sedation for short procedures or imaging.
        • Propofol is often given with an opioid, as propofol does not address pain from noxious procedures. [Chidambaran, 2015]
        • Intermittent bolus administration has greater risk than continuous infusion. [Chidambaran, 2015]
        • Propofol has also been safely used in PICUs for RSI and airway management and for short periods at low dosages. [Rosenfeld-Yehoshua, 2016]
      • In the ICU, may be used for prolonged sedation. [Chidambaran, 2015; Cornfield, 2002]
        • Prolonged use may lead to hypertriglyceridemia and pancreatitis.
        • Risk factor for Propofol Infusion Syndrome

 

Problem with Propofol: Propofol Infusion Syndrome

  • Adverse reactions can occur with Propofol (just like any medication)
    • Pain at injection site – most common side-effect [Chidambaran, 2015]
    • Anaphylaxis [Chidambaran, 2015]
    • Mitochondrial function depression [Chidambaran, 2015]
      • Propofol can uncouple oxidative phosphorylation.
      • Mechanism is yet unclear.
      • May play role in Propofol Infusion Syndrome.
  • “Propofol Infusion Syndrome”:
    • Very rare, but deadly complication coincident with Propofol administration.
      • True incidence is unknown
      • May be an extreme manifestation of a more common and initially reversible physiologic state. [Diedrich, 2011]
      • Causation or mechanism has, as yet, not been determined.
    • Clinical Features: [Diedrich, 2011]
      • Cardiovascular
        • Hypotension
        • Dysrhythmias (ex, Bradycardia, Wide QRS, Brugada-like ECG, VTach, PEA, asystole)
        • Myocardial Failure
      • Metabolic
        • Hyperthermia
        • Metabolic Acidosis
      • Renal and Musculoskeletal
      • Hepatic
        • Hepatomegaly and Transaminitis
        • Hypertriglyceridemia and Lipdemia

 

Propofol Infusion Syndrome: Risk Factors

Through evaluation of the case reports and case series, there appears to be several trends for Risk Factors (although, there are also outliers). [Diedrich, 2011; Okamoto, 2003]

  • Dose of Propofol >4 mg/kg/hr
  • Duration of Propofol 48 hours or greater
  • Patients with Inborn Errors of Metabolism
  • Concomitant infusion of Vasopressors
  • Concomitant use of Steroids
  • Patients with “Critical Illness”
  • “Younger” Age – although death seemed to more likely occur in patients >18 years of age.

 

Propofol Infusion Syndrome: Treatment

  • There is no specific therapy for Propofol Infusion Syndrome.
    • Awareness of it and attempting to prevent it is best option. [Diedrich, 2011]
    • Some recommend monitoring serum lactate levels… but, this obviously is not a diagnostic test.
    • Maintaining an adequate carbohydrate load to prevent the increase in fatty acids, hopefully reducing risk. [Chidambaran, 2015]
  • Propofol Infusion Syndrome is a diagnosis of exclusion!
    • The critically ill patient has many reasons to develop the same clinical features.
    • Treat all potential etiologies aggressively (ex, sepsis).
  • Supportive Care: [Diedrich, 2011]
    • Stop the propofol once suspicious for this.
    • Improve gas exchange
    • Cardiac pacing if bradycardic
    • Consider glucagon and phosphodiesterase inhibitors
    • Hemodialysis
    • ECMO

 

Moral of the Morsel

  • Match your Patients and the Sedatives. As best you are able, consider which medication is right for each specific patient. There is no one perfect medication for everyone.
  • Propofol is Powerful. And with great power, comes great responsibility. Use this tool wisely.
  • Don’t discount your colleagues’ experience. While we may have not encountered Propofol Infusion Syndrome in the ED, the PICU’s experience may be different.
  • Don’t throw the Propofol out with the Bathwater. Over short durations, using appropriate dosages, and in the right patients, the risk of Propofol Infusion Syndrome is likely lower than the risk of the child dislodging the ETT you just placed. Evaluate your risk assessment scales wisely.

 

References

Kang P1, Jang YE1, Kim EH1, Lee JH1, Kim JT1,2, Kim HS1,2. Safety and efficacy of propofol anesthesia for pediatric target-controlled infusion in children below 3 years of age: a retrospective observational study. Expert Opin Drug Saf. 2018 Sep 15:1-7. PMID: 30221553. [PubMed] [Read by QxMD]

Indra S1, Haddad H, OʼRiordan MA. Short-Term Propofol Infusion and Associated Effects on Serum Lactate in Pediatric Patients. Pediatr Emerg Care. 2017 Nov;33(11):e118-e121. PMID: 29095778. [PubMed] [Read by QxMD]

Rosenfeld-Yehoshua N1, Klin B, Berkovitch M, Abu-Kishk I. Propofol Use in Israeli PICUs. Pediatr Crit Care Med. 2016 Mar;17(3):e117-20. PMID: 26741413. [PubMed] [Read by QxMD]

Chidambaran V1, Costandi A, D’Mello A. Propofol: a review of its role in pediatric anesthesia and sedation. CNS Drugs. 2015 Jul;29(7):543-63. PMID: 26290263. [PubMed] [Read by QxMD]

Chiaretti A1, Benini F, Pierri F, Vecchiato K, Ronfani L, Agosto C, Ventura A, Genovese O, Barbi E. Safety and efficacy of propofol administered by paediatricians during procedural sedation in children. Acta Paediatr. 2014 Feb;103(2):182-7. PMID: 24138461. [PubMed] [Read by QxMD]

Rajasekaran S1, Hackbarth RM, Davis AT, Kopec JS, Cloney DL, Fitzgerald RK, Hassan NE, Ndika AN, Cornelius K, McCullough A, Sanfilippo D. The safety of propofol sedation for elective nonintubated esophagogastroduodenoscopy in pediatric patients. Pediatr Crit Care Med. 2014 Jul;15(6):e261-9. PMID: 24849145. [PubMed] [Read by QxMD]

Diedrich DA1, Brown DR. Analytic reviews: propofol infusion syndrome in the ICU. J Intensive Care Med. 2011 Mar-Apr;26(2):59-72. PMID: 21464061. [PubMed] [Read by QxMD]

Meyer P1, Langlois C, Soëte S, Leydet J, Echenne B, Rivier F, Bonafé A, Roubertie A. Unexpected neurological sequelae following propofol anesthesia in infants: Three case reports. Brain Dev. 2010 Nov;32(10):872-8. PMID: 20060673. [PubMed] [Read by QxMD]

Vespasiano M1, Finkelstein M, Kurachek S. Propofol sedation: intensivists’ experience with 7304 cases in a children’s hospital. Pediatrics. 2007 Dec;120(6):e1411-7. PMID: 18055659. [PubMed] [Read by QxMD]

Timpe EM1, Eichner SF, Phelps SJ. Propofol-related infusion syndrome in critically ill pediatric patients: coincidence, association, or causation? J Pediatr Pharmacol Ther. 2006 Jan;11(1):17-42. PMID: 23118644. [PubMed] [Read by QxMD]

Wheeler DS1, Vaux KK, Ponaman ML, Poss BW. The safe and effective use of propofol sedation in children undergoing diagnostic and therapeutic procedures: experience in a pediatric ICU and a review of the literature. Pediatr Emerg Care. 2003 Dec;19(6):385-92. PMID: 14676486. [PubMed] [Read by QxMD]

Okamoto MP1, Kawaguchi DL, Amin AN. Evaluation of propofol infusion syndrome in pediatric intensive care. Am J Health Syst Pharm. 2003 Oct 1;60(19):2007-14. PMID: 14531250. [PubMed] [Read by QxMD]
Cornfield DN1, Tegtmeyer K, Nelson MD, Milla CE, Sweeney M. Continuous propofol infusion in 142 critically ill children. Pediatrics. 2002 Dec;110(6):1177-81. PMID: 12456916. [PubMed] [Read by QxMD]

Festa M1, Bowra J, Schell D. Use of propofol infusion in Australian and New Zealand paediatric intensive care units. Anaesth Intensive Care. 2002 Dec;30(6):786-93. PMID: 12500519. [PubMed] [Read by QxMD]

Sean M. Fox

I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renown educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.

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