It was with great interest that we read the article by Cravens et al.  1on the incidence of propofol infusion syndrome. This is obviously an important question with significant clinical relevance. However, with all of the inherent limitations of a retrospective study as recognized by the authors, we find the interpretation and conclusion of the authors (“this study provides evidence that even in a non–critically ill population, prolonged high-dose propofol infusion is associated with otherwise unexplained metabolic acidosis in a significant number of patients”) to be inconsistent with the limited data presented.

To begin, their definition of metabolic acidosis is problematic, because it merely represents the upper limit of the reference range for base excess. We understand that the definition of metabolic acidosis might be tricky, particularly if bicarbonate and chloride are unknown. However, the definition should meet the generally accepted criterion, and base excess should be lower than, and not equal to, −2 mEq/l.2As it were, 2 of 13 patients with “propofol infusion syndrome” really had a normal base excess (=−2), and 4 patients had a base excess of −2, which is nearly normal (fig. 1 in the article).

Of the cohort of 301 patients, only 55 patients had arterial blood gases drawn at various stages because of concern with their respiratory status. The authors argue that this may underestimate, and not overestimate, the incidence of “propofol infusion syndrome.” We respectfully disagree. A more appropriate interpretation is that the incidence remains unknown, because the factors that predispose these individuals to respiratory depression may also have resulted in the metabolic acidosis. Without a control group, the influence of this built-in bias simply cannot be assessed.

Another problem relates to the variability of blood sampling timing and the lack of baseline data. The authors’ figure 1 shows that one patient had base excess of −6 at a very low rate of propofol infusion. Without baseline blood gases and knowledge of the total dose of propofol infused, the authors cannot consider this patient to have propofol infusion syndrome. Moreover, because in all patients the timing of blood sampling is not reported and baseline blood gases are not available, the data in figure 1 are essentially uninterpretable, and one wonders why the plot was made at all. Similarly, the data displayed in their table 2 regarding duration of propofol infusion is not meaningful because the crucial time is the duration of infusion (and amount of propofol given) at the time of blood gas sampling, not the total duration of the infusion for the procedure. About the only fact we can be certain of is that the authors overestimate the duration of propofol infusion before the development of this mild metabolic acidosis, which may not have any relation to the propofol infusion.

Propofol infusion syndrome is diagnosed in cases of unexplained severe metabolic, usually lactic, acidosis and is associated with high-dose3–5or long-duration propofol infusion,6,7usually both.8,9We are surprised that Cravens et al.  titled their work as “Incidence of Propofol Infusion Syndrome during …,” because the study did not include any patient who developed frank propofol infusion syndrome. Finally, to conclude that “this study provides evidence that even in a non–critically ill population, prolonged high-dose propofol infusion is associated with otherwise unexplained metabolic acidosis in a significant number of patients” is a stretch of one’s imagination. Not only was the duration of propofol infusion before the development of metabolic acidosis unknown, the dose of propofol given was a sedative dose and could hardly qualify as high dose by any clinical standard.

To be fair, as the authors indicated, it is difficult to draw definitive conclusions from a retrospective study. However, they should be valid if not definitive. We performed a similar retrospective chart review, comparing lactate, bicarbonate, chloride, arterial carbon dioxide tension, pH, and other parameters in patients receiving high-dose propofol anesthesia (n = 50) and volatile anesthesia (n = 100) over time in long-duration spine surgeries, and we observed that lactate levels are significantly lower during propofol infusion anesthesia.10The manuscript is currently in preparation. We do fully agree with Cravens et al.  on one aspect: A larger prospective study is warranted to look for early signs of propofol infusion syndrome and its incidence.

*Harborview Medical Center, University of Washington, Seattle, Washington.

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Burow BK, Johnson ME, Packer DL: Metabolic acidosis associated with propofol in the absence of other causative factors. Anesthesiology 2004; 101:239–41
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Salengros JC, Velghe-Lenelle CE, Bollens R, Engelman E, Barvais L: Lactic acidosis during propofol–remifentanil anesthesia in an adult. Anesthesiology 2004; 101:241–3
Cremer OL, Moons KG, Bouman EA, Kruijswijk JE, de Smet AM, Kalkman CJ: Long-term propofol infusion and cardiac failure in adult head-injured patients. Lancet 2001; 357:117–8
Merz TM, Regli B, Rothen HU, Felleiter P: Propofol infusion syndrome: A fatal case at a low infusion rate. Anesth Analg 2006; 103:1050
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Tontisirin N, Rozet I, Vavilala MS, Lee LA, Lam AM: Lactate levels during long spine surgery: Comparison between propofol infusion and volatile anesthetics. J Neurosurg Anesthesiol 2006; 18:311