Skip to main content

Advertisement

SpringerLink
Log in

The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome

  • Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Propofol infusion syndrome (PRIS) is a rare and often fatal syndrome described in critically ill children undergoing long-term propofol infusion at high doses. Recently several cases have been reported in adults, too. The main features of the syndrome consist of cardiac failure, rhabdomyolysis, severe metabolic acidosis and renal failure. To date 21 paediatric cases and 14 adult cases have been described. These latter were mostly patients with acute neurological illnesses or acute inflammatory diseases complicated by severe infections or even sepsis, and receiving catecholamines and/or steroids in addition to propofol. Central nervous system activation with production of catecholamines and glucocorticoids, and systemic inflammation with cytokine production are priming factors for cardiac and peripheral muscle dysfunction. High-dose propofol, but also supportive treatments with catecholamines and corticosteroids, act as triggering factors. At the subcellular level, propofol impairs free fatty acid utilisation and mitochondrial activity. Imbalance between energy demand and utilisation is a key pathogenetic mechanism, which may lead to cardiac and peripheral muscle necrosis.

Propofol infusion syndrome is multifactorial, and propofol, particularly when combined with catecholamines and/or steroids, acts as a triggering factor. The syndrome can be lethal and we suggest caution when using prolonged (>48 h) propofol sedation at doses higher than 5 mg/kg per h, particularly in patients with acute neurological or inflammatory illnesses. In these cases, alternative sedative agents should be considered. If unsuitable, strict monitoring of signs of myocytolysis is advisable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  1. Parke TJ, Stevens JE, Rice AS, Greenaway CL, Bray RJ, Smith PJ, Waldmann CS, Verghese C (1992) Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five reports. BMJ 305:613–616

    CAS  PubMed  Google Scholar 

  2. Strikland RA, Murray MJ (1995) Fatal metabolic acidosis in paediatric patient receiving an infusion of propofol in the intensive care unit: is there a relationship? Crit Care Med 23:405–409

    Google Scholar 

  3. Van Straaten EA, Hendriks JJE, Ramsey G, Vos GD (1996) Rhabdomyolysis and pulmonary hypertension in a child, possibly due to long-term high-dose propofol infusion. Crit Care Med 22:997–1001

    Google Scholar 

  4. Cray SH, Robinson BH, Cox PN (1998) Lactic acidemia and bradyarrhythmia in a child sedated with propofol. Crit Care Med 26:2089–2092

    Google Scholar 

  5. Hanna JP, Ramundo ML (1998) Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children. Neurology 50:301–303

    CAS  PubMed  Google Scholar 

  6. Bray RJ (1998) Propofol infusion syndrome in children. Paediatr Anaesth 8:491–499

    Article  CAS  PubMed  Google Scholar 

  7. Bray RJ (1999) Fatal myocardial failure associated with a propofol infusion in a child. Anaesthesia 50:94

    Google Scholar 

  8. Hatch DJ (1999) Propofol-infusion syndrome in children. Lancet 353:1117–1118

    Article  CAS  PubMed  Google Scholar 

  9. Murdoch SD, Cohen AT (1999) Propofol-infusion syndrome in children. Lancet 353:2074–2075

    CAS  Google Scholar 

  10. Bray RJ (1999) Propofol-infusion syndrome in children. Lancet 353:2074

    CAS  Google Scholar 

  11. Mehta N, DeMunter C, Habibi P, Nadel S, Britto J (1999) Short-term propofol infusions in children. Lancet 354:866–867

    Article  CAS  PubMed  Google Scholar 

  12. Wolf A, Weir P, Segar P, Stone J, Shield J (2001) Impaired fatty acid oxidation in propofol infusion syndrome. Lancet 357:606–607

    Article  CAS  PubMed  Google Scholar 

  13. Cannon ML, Steven SG, Bauman LA (2001) Metabolic acidosis, rhabdomyolysis and cardiovascular collapse after prolonged propofol infusion. J Neurosurg 95:1053–1056

    CAS  PubMed  Google Scholar 

  14. Valente JF, Anderson GL, Branson RD, Johnson DJ, Davis K, Porembka DT (1994) Disadvantages of prolonged propofol sedation in the critical care unit. Crit Care Med 22:710–712

    CAS  PubMed  Google Scholar 

  15. Newman LJ, McDonald JC, Wallace PGM, Ledingham IMcA (1987) Propofol infusion for sedation in intensive care. Anaesthesia 42:929–937

    CAS  PubMed  Google Scholar 

  16. Farling PA, Johnston JR, Coppel DL (1989) Propofol infusion for sedation of patients with head injury in intensive care. Anaesthesia 44:222–226

    CAS  PubMed  Google Scholar 

  17. Aitkenhead AR, Willatts SM, Park GR, Collins CH, Ledingham IMcA, Pepperman ML, Coates PD, Bodenham AR, Smith MB, Wallace PGM (1989) Comparison of propofol and midazolam for sedation in critically ill patients. Lancet 2:704–709

    CAS  PubMed  Google Scholar 

  18. Bailie GR, Cockshott ID, Douglas EJ, Bowles BMJ (1992) Pharmacokinetics of propofol during and after long term continuous infusion for maintenance of sedation in ICU patients. Br J Anaesth 68:486–491

    CAS  PubMed  Google Scholar 

  19. Carrasco G, Mollina R, Costa J, Soler JM, Cabrè L (1993) Propofol vs Midazolam in short-, medium-, long-term sedation of critically ill patients. Chest 103:557–564

    CAS  PubMed  Google Scholar 

  20. Chamorro C, de Latorre FJ, Montero A, Sanchez-Izquiedro J, Jareno A, Gonzalez E, Barrios M, Carpintero JL, Martin-Santos F, Otero B, Ginestal R (1996) Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomised, multicenter trial. Crit Care Med 24:932–939

    CAS  PubMed  Google Scholar 

  21. Buckley PM (1997) Propofol in patients needing long-term sedation in intensive care: an assessment of the development of tolerance. Intensive Care Med 23:974

    Article  PubMed  Google Scholar 

  22. Sanchez-Izquierdo-Riera JA, Caballero-Cubedo RE, Perez-Vela JL, Ambros-Checa A, Cantalpiedra-Santiago JA, Alted-Lopez E (1998) Propofol versus midazolam: safety and efficacy for sedating the severe trauma. Anesth Analg 86:1219–1224

    CAS  PubMed  Google Scholar 

  23. Kelly DF, Goodale DB, Williams J, Herr DL, Chappell ET, Rosner MJ, Jacobson J, Levy ML, Croce MA, Maniker AH, Fulda GJ, Lovett JV, Mohan O, Narayan RK (1999) Propofol in the treatment of moderate and severe head injury: a randomised prospective double-blinded pilot trial. J Neurosurg 90:1042–1052

    CAS  PubMed  Google Scholar 

  24. Marinella MA (1996) Lactic acidosis associated with propofol. Chest 109:292

    CAS  PubMed  Google Scholar 

  25. Stelow EB, Johari VP, Smith SA, Crosson JT, Apple FS (2000) Propofol-associated rhabdomyolysis with cardiac involvement in adults: chemical and anatomic findings. Clin Chem 46:577–581

    CAS  PubMed  Google Scholar 

  26. Perrier ND, Baerga-Varela Y, Murray MJ (2000) Death related to propofol use in an adult patient. Crit Care Med 28:3071–3074

    CAS  PubMed  Google Scholar 

  27. Cremer OL, Moons KGM, Bouman EAC, Kruijiswijk JE, de Smet AM, Kalkman CJ (2001) Long-term propofol infusion and cardiac failure in adult head-injured patients. Lancet 357:117–118

    Article  CAS  PubMed  Google Scholar 

  28. Kelly DF (2001) Propofol infusion syndrome. J Neurosurg 95:925–926

    CAS  PubMed  Google Scholar 

  29. Friedman JA, Manno E, Fulgham JR (2002) Propofol. J Neurosurg 96:1161–1162

    PubMed  Google Scholar 

  30. Latronico N (1997) Acute myopathy of intensive care. Ann Neurol 42:131–132

    CAS  PubMed  Google Scholar 

  31. Branca D, Roberti MS, Lorenzin P, Vincenti E, Scutari G (1991) Influence of the anaesthetic 2,6.Diisopropylphenol on the oxidative phosphorylation of isolated rat liver mitochondria. Biochem Pharmacol 42:87–90

    Article  CAS  PubMed  Google Scholar 

  32. Schenkman KA, Yan S (2000) Propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectroscopy. Crit Care Med 28:172–177

    CAS  PubMed  Google Scholar 

  33. Zhou W, Fontenot HJ, Wang SN, Kennedy RH (1999) Propofol-induced alterations in myocardial beta-adrenoceptor binding and responsiveness. Anesth Analg 89:604–608

    CAS  PubMed  Google Scholar 

  34. Zhou W, Fontenot HJ, Liu S, Kennedy RH (1997) Modulation of cardiac calcium channels by propofol. Anesthesiology 86:670–675

    CAS  PubMed  Google Scholar 

  35. Roe CR, Coates PM (1995) Mitochondrial fatty acid oxidation disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited diseases, 7th edition. McGraw-Hill, New York, pp 1501–1533

  36. Jouven X, Charles MA, Desnos M, Ducimetiere P (2001) Circulating nonesterified fatty acid level as a predictive risk factor for sudden death in the population. Circulation 104:756–761

    CAS  PubMed  Google Scholar 

  37. Myburgh JA, Upton RN, Grant C, Martinez A (2001) Epinephrine, norepinephrine and dopamine infusions decrease propofol concentrations during continuous propofol infusion in an ovine model. Intensive Care Med 27:276–282

    Google Scholar 

  38. Rona G (1985) Catecholamine cardiotoxicity. J Mol Cell Cardiol 17:291–306

    CAS  PubMed  Google Scholar 

  39. Samuels MA, Southern JF (1988) Case records of the Massachusetts General Hospital case 15–1988. N Engl J Med 318:970–981

    PubMed  Google Scholar 

  40. Cebelin M, Hirsch CS (1980) Human stress cardiomyopathy. Hum Pathol 11:123–132

    CAS  PubMed  Google Scholar 

  41. Braunwald E, Kloner RA (1985) Myocardial reperfusion: a double-edged sword? J Clin Invest 76:1713–1719

    Google Scholar 

  42. Baroldi G (1975) Different morphological types of myocardial cell death in man. In: Fleckstein A, Rona G (eds) Recent advances in studies of cardiac structure and metabolism, pathophysiology and morphology of myocardial cell alteration, Vol 6. University Park Press, Baltimore, pp 385–397

  43. Karch SB, Billingham ME (1986) Myocardial contraction band revisited. Hum Pathol 17:9-13

    CAS  PubMed  Google Scholar 

  44. Drislane FW, Samuels MA, Kozakewich H, Schoene J, Strunk RC (1987) Myocardial contraction band lesions in patients with fatal asthma: possible neurocardiologic mechanisms. Am Rev Respir Dis 135:498–501

    CAS  PubMed  Google Scholar 

  45. Riedel T, Sojcic SG, Pfenninger J (2002) Fatal catecholamine myocarditis in a child with severe scalding injury. Intensive Care Med 28:1687–1688

    Article  Google Scholar 

  46. Herndon DN, Hart DV, Wolf SE, Chinkes DL, Wolfe RR (2001) Reversal of catabolism by beta-blockade after severe burns. N Engl J Med 345:1223–1229

    CAS  PubMed  Google Scholar 

  47. De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphael JC, Outin H, Bastuji-Garin S (2002) Paresis acquired in the intensive care unit. A prospective multicenter study. JAMA 288:2859–2867

    PubMed  Google Scholar 

  48. Latronico N (2003) Paresis following mechanical ventilation. JAMA 289:1633–1634

    Google Scholar 

  49. Mitch WE, Goldberg AL (1996) Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. New Engl J Med 335:1897–1905

    Article  PubMed  Google Scholar 

  50. Fink MP, Evans TW (2002) Mechanisms of organ dysfunction in critical illness: report from a Round Table Conference held in Brussels. Intensive Care Med 28:369–375

    Article  Google Scholar 

  51. Bone RC (1996) Immunological dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Ann Intern Med 125:680–687

    CAS  PubMed  Google Scholar 

  52. Turner A, Tsamitros M, Bellomo R (1999) Myocardial cell injury in septic shock. Crit Care Med 27:1775–1780

    CAS  PubMed  Google Scholar 

  53. Grocott-Mason RM, Shah AM (1998) Cardiac dysfunction in sepsis: new theories and clinical implications. Intensive Care Med 24:286–295

    Article  CAS  PubMed  Google Scholar 

  54. Ammann P, Fehr T, Minder EI, Gunter C, Bertel O (2001) Elevation of troponin I in sepsis and septic shock. Intensive Care Med 27:965–969

    Google Scholar 

  55. Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ (1984) Polyneuropathy in critically ill patients. J Neurol Neurosurg Psych 47:1223–1231

    CAS  PubMed  Google Scholar 

  56. Latronico N, Fenzi F, Recupero D, Guarneri B, Tomelleri G, Tonin P, De Maria G, Antonini L, Rizzuto N, Candiani A (1996) Critical illness myopathy and neuropathy. Lancet 347:1579–1582

    CAS  PubMed  Google Scholar 

  57. Latronico N, Candiani A (1998) Muscular wasting as a consequence of sepsis. In: Gullo A (ed) Anaesthesia, pain, intensive care and emergency medicine, A.P.I.C.E. 13. Springer, Milano, pp 517–522

  58. Meldrum DR (1998) Tumor necrosis factor in the heart. Am J Physiol 274:R577–595

    CAS  PubMed  Google Scholar 

  59. Shapiro L, Gelfand JA (1995) Cytokines. In: Shoemaker, Ayres, Grenvik, Holbrook (eds) Textbook of critical care, 3rd edn. Saunders, Philadelphia, pp 154–161

  60. Samuels MA (1993) Cardiopulmonary aspects of acute neurologic diseases. In: Ropper A (ed) Neurological and neurosurgical intensive care, 3rd edn. Raven Press, New York, pp 103–119

  61. Oppenheimer SM, Wilson JX, Guiraudon C, Cechetto DF (1991) Insular cortex stimulation produces lethal cardiac arrhythmias: a mechanism of sudden death. Brain Res 550:115–121

    Article  CAS  PubMed  Google Scholar 

  62. Cheung RTF, Hachinski V (2000) The insula and cerebrogenic sudden death. Arch Neurol 57:1685–1688

    Article  CAS  PubMed  Google Scholar 

  63. Elenkov IJ, Wilder RL, Chrousos GP, Vizi SE (2000) The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52:595–638

    CAS  PubMed  Google Scholar 

  64. Task Force of the American College of Critical Care Medicine of the Society of Critical Care Medicine (2002) Clinical Practice Guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 30:119–141

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Anesthesiology—Intensive Care, University of Brescia, Piazzale Ospedali Civili 1, 25125 , Brescia, Italy

    Beatrice Vasile, Frank Rasulo, Andrea Candiani & Nicola Latronico

Authors
  1. Beatrice Vasile
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank Rasulo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Candiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicola Latronico
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola Latronico.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vasile, B., Rasulo, F., Candiani, A. et al. The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med 29, 1417–1425 (2003). https://doi.org/10.1007/s00134-003-1905-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-003-1905-x

Keywords

Search

Navigation