Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-19T07:16:03.589Z Has data issue: false hasContentIssue false
  • English
  • Français

The ‘propofol infusion syndrome’: the facts, their interpretation and implications for patient care

Published online by Cambridge University Press:  29 August 2006

K. Ahlen ,
C. J. Buckley ,
D. B. Goodale  and
A. H. Pulsford
K. Ahlen
Affiliation:
AstraZeneca R&D, Clinical Science, Sweden
C. J. Buckley
Affiliation:
AstraZeneca R&D, Clinical Development, Cheshire, UK
D. B. Goodale
Affiliation:
AstraZeneca Pharmaceuticals, Medicine and Science, Wilmington, DE, USA
A. H. Pulsford
Affiliation:
AstraZeneca R&D, Neuroscience, Cheshire, UK
Get access

Abstract

Summary

AstraZeneca (the manufacturer of Diprivan™) presents its review of the history of the so-called ‘propofol infusion syndrome’, highlighting the difficulties in analysing the incomplete information available. Theories as to its causality are presented and discussed; these include mitochondrial toxicity, mitochondrial defects, impaired tissue oxygenation and carbohydrate deficiency. A review of published and confidential safety data is presented and discussed; it concludes that the major risk factors for its development appear to be poor oxygen delivery, sepsis, serious cerebral injury and high propofol dosage. In some reports an increasing lipaemia was noted and was likely to be due to a failure of hepatic lipid regulation, possibly related to poor oxygenation and/or possibly a lack of glucose. In some cases an increasing lipaemia was the first indication of impending ‘propofol infusion syndrome’ onset and it should not be viewed as a benign sign. The lipaemia can lead to sequestration of propofol into the lipid phase, leading to lowered free propofol levels and apparent insensitivity to propofol. In conclusion AstraZeneca advocates good haemodynamic and oxygen delivery management, adequate glucose provision, adherence to recommended propofol dosing regimes together with active management of lipaemias to both prevent and treat ‘propofol infusion syndrome’.

Keywords

PROPOFOLINTRAVENOUS ANAESTHESIASEDATIONCRITICAL CAREDRUG TOXICITY
Type
Review
Information
European Journal of Anaesthesiology , Volume 23 , Issue 12 , December 2006 , pp. 990 - 998
Copyright
2006 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Parke TJ, Stevens JE, Rice ASCet al. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. BMJ 1992; 305: 613–616.Google Scholar
Anonymous. Side-effects of propofol (Diprivan). Ugeskr. Laeger 1990; 152(16): 1176.
FDA Reports 1992; 54: 14.
Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth 1998; 8: 491–499.Google Scholar
Hatch DJ. Propofol-infusion syndrome in children. Lancet 1999; 353: 1117–1118.Google Scholar
Cremer OL, Moons KGM, Bouman EACet al. Long-term propofol infusion and cardiac failure in adult head-injured patients. Lancet 2001; 357: 117–118.Google Scholar
Friedman JA, Manno E, Fulgham JR. Propofol. J Neurosurg 2002; 96: 1161–1162.Google Scholar
Prasad A, Worrall B, Bertram Eet al. Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 2001; 42: 380–386.Google Scholar
Cornfield DN, Tegtmeyer K, Nelson MD, Milla CE, Sweeney M. Continuous propofol infusion in 142 critically ill children. Pediatrics 2002; 110: 1177–1181.Google Scholar
Pepperman ML, Macrae D. A comparison of propofol and other sedative use in paediatric intensive care in the United Kingdom. Paediatr Anaesth 1997; 7: 143–153.Google Scholar
Cook S. Propofol infusion in children. BMJ 1992; 305: 952.Google Scholar
Cruickshank JM. Reduction of stress/catecholamine-induced cardiac necrosis by beta1 selective blockade. Lancet 1987; 2: 585–589.Google Scholar
Dixit S, Castle M, Velu RPet al. Cardiac involvement in patients with acute neurological disease. Confirmation with cardiac Troponin 1. Arch Intern Med 2000; 160: 3153–3158.Google Scholar
Tse H-F, Yeung C-K. From profound hypokalaemia to fatal rhabdomyolysis after severe head injury. Am J Med 2000; 109: 599–600.Google Scholar
Feinberg MS, Di Segni E, Freimark Det al. Transient left ventricular outflow tract obstruction and pseudohypertrophy due to severe hypovolaemia and catecholamine administration in a potential donor for heart transplantation. J Cardiovasc Diagn Proced 1999; 16: 125–129.Google Scholar
Perkin RM, Anas N, Lubinsky P. Myocardial ischaemia and disparate ventricular function after paediatric head injury. Crit Care Med 1991; 19: 587–588.Google Scholar
Schranz D, Stopfkuchen H, Jungst BK. Hämorrhagisches Lungenödem und Herzkreislaufinsuffizienz nach isoliertem Schadelhirntrauma. Monatsschr Kinderheilkd 1981; 129: 248–250.Google Scholar
Gustafsson U, Wardell K, Nilsson GEet al. Vasomotion in rat skeletal muscle induced by hemorrhage as recorded by laser-Doppler flowmetry. Microvasc Res 1991; 42: 224–228.Google Scholar
Siegemund M, van Bommel J, Racovitza Iet al. Sepsis, microcirculation and vasodilators. Nederlandse Vereniging voor Intensive Care 2002; 6(5); 12–16.Google Scholar
Balasubramanian V, Townsend S, Boots RJ. Does splanchnic ischaemia occur in isolated neurotrauma? A prospective observational study. Crit Care Med 1999; 27: 1175–1180.Google Scholar
Vitale GC, Larson GM, Davidson PRet al. Analysis of hyperamylasemia in patients with severe head injury. J Surg Res 1987; 43: 226–233.Google Scholar
Gayan-Ramirez G, Decramer M. The effect of corticotherapy on respiratory muscles. Revue des Maladies Respiratoires 1998; 15: 33–41.Google Scholar
Reichhart MD, Lobrinus JA, Kuntzer Tet al. Acquired neuromuscular disorders in critically ill patients. (Les complications neuromusculaires acquises de reanimation.) Med Hyg 2003; 61: 970–976.Google Scholar
Knibbe CAJ, Zuideveld KP, Dejongh J, Kuks PFM, Aarts LPHJ, Danhof M. Population pharmacokinetic and pharmacodynamic modeling of propofol for long-term sedation in critically ill patients: a comparison between propofol 6% and propofol 1%. Clin Pharmacol Therap 2002; 72(6); 670–684.Google Scholar
Rigoulet M, Devin A, Averet Net al. Mechanisms of inhibition and uncoupling of respiration in isolated rat liver mitochondria by the general anesthetic 2,6-diisopropylphenol. Eur J Biochem 1996; 241: 280–285.Google Scholar
Schenkman KA, Yan S. Propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectroscopy. Crit Care Med 2000; 28: 172–177.Google Scholar
Kress JP, O'Connor MF, Pohlman ASet al. Sedation of critically ill patients during mechanical ventilation: a comparison of propofol and midazolam. Am J Resp Crit Care Med 1996; 153: 1012–1018.Google Scholar
Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet 2001; 357(9256): 606–607.Google Scholar
Withington DE, Decell MK, Ayed TA. A case of propofol toxicity, further evidence for a causal mechanism. Pediatr Anesth 2004; 14: 505–508.Google Scholar
Wolf AR, Potter F. Propofol infusion in children: when does an anesthetic tool become an intensive care liability? Pediatr Anesth 2004; 14: 435–438.Google Scholar
Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intens Care Med 2003; 29: 1417–1425.Google Scholar
Corr PB, Creer MH, Yamada KA, Saffitz JE, Sobel BE. Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation. J Clin Invest 1989; 83: 927–936.Google Scholar
Bonnefont JP, Djouadi F, Prip-Buus C, Gobin S, Munnich A, Bastin J. Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Mol Aspects Med 2004; 25: 495–520.Google Scholar
Roth MS, Martin AB, Katz JA. Nutritional implications of prolonged propofol use. Am J Health-Syst Pharm 1997; 54: 694–695.Google Scholar
Wasserberger J, Ordog GJ, Shoemaker WC. Inadequate critical care curriculum in pediatric emergency medicine fellowships. Acad Emerg Med 1994; 1: 503.Google Scholar
Zornow MH, Prough DS. Fluid management in patients with traumatic brain injury. New Hori Sci Pract Acute Med 1995; 3: 488–498.Google Scholar
Manley G, Knudson MM, Morabito Det al. Hypotension, hypoxia and head injury – frequency, duration and consequences. Arch Surg 2001; 136: 1118–1123.Google Scholar
Bingham WF. The limits of cerebral dehydration in the treatment of head injury. Surg Neurol 1986; 25: 340–345.Google Scholar
Luerssen TG, Wolfla CE. Pathophysiology and management of increased intracranial pressure in children (Chapter 4). In: Andrews BT, Hammer GB, eds. Pediatric Neurosurgical Intensive Care. Neurosurgical Topics Series. AANS Publications Committee. The American Association of Neurological Surgeons.New York: Thieme Medical Publishers, 1997. ISBN-10: 1879284456/3131324813.