Correspondence  |   March 2002
Propofol, Metabisulfite, and Bronchoconstriction
Author Notes
  • University of California, San Francisco, California.
Article Information
Correspondence   |   March 2002
Propofol, Metabisulfite, and Bronchoconstriction
Anesthesiology 3 2002, Vol.96, 771-772. doi:
Anesthesiology 3 2002, Vol.96, 771-772. doi:
To the Editor:—
Brown et al.  1 found that infusion of propofol with or without metabisulfite into the bronchial artery does not alter airway resistance. However, they also found that propofol without metabisulfite can attenuate bronchoconstriction produced by vagal nerve stimulation and that the addition of metabisulfite can reverse this effect. Commenting on these results, “This Month in Anesthesiology” suggested that “[The] preservative used in propofol can have an effect on the ability of propofol to attenuate bronchoconstriction.”2 
Three observations may be made regarding these results. First, the effect was small. In the presence of vagal nerve stimulation, a 0.06-ml/min propofol infusion without metabisulfite decreased airway resistance by 16 ± 15% (mean ± SD). The same infusion with metabisulfite decreased airway resistance by 5 ± 8% (difference not significant by an unpaired t  test). At an infusion rate of 0.2 ml/min, the decreases were 29 ± 10 and 2 ± 16%, respectively (P  < 0.01), and at an infusion rate of 0.6 ml/min, they were 42 ± 10 and 13 ± 23% (P  < 0.05). Methacholine infusion produced trends similar to those seen with vagal nerve stimulation, but no individual pair of results differed significantly.
Second, the metabisulfite concentration in the bronchial artery resulting from direct continuous (10 min) infusion into the artery may considerably exceed the concentration that would result in well-perfused tissues (e.g.  , bronchi and brain) from an intravenous injection for induction of anesthesia. Blood flow through the bronchial artery in sheep has been measured at 25.3 ± 5.2 ml/min. 3 Infusion of 0.06, 0.2, and 0.6 ml/min of 5 mg/ml propofol (plus 0.125 mg/ml metabisulfite) gives concentrations of 11.9, 39.5, and 118.6 μg/ml propofol, respectively (or 6.7 × 10−5, 2.2 × 10−4, and 6.7 × 10−4m). These concentrations are modestly less than (80% of) those calculated by Brown et al.  1 (8.4 × 10−5, 2.8 × 10−4, and 8.4 × 10−4m), possibly because the sheep in the article defining bronchial artery blood flow were larger (35–50 kg) than those used by Brown et al.  1 (30 kg). In 50-kg sheep given 100 mg propofol intravenously, the peak brain and sagittal sinus concentrations of propofol equal approximately 5 μg/ml, 4 and the steady-state concentration at which 95% of 20- to 55-yr-old patients do not respond to command is 5.4 μg/ml propofol. 5 Thus, the lowest concentration applied by Brown et al.  , 1 one that did not result in a statistically significant difference between propofol with and without metabisulfite, is twice the concentration required for loss of consciousness in humans. The concentrations that did produce statistically significant differences are approximately 7 and 22 times the concentrations required for loss of consciousness.
Third, “Propofol without metabisulfite…, propofol with metabisulfite …, and lidocaine … were administered in concentrations of 5 mg/ml.”1Such a concentration of propofol is half that used for induction of anesthesia. Did the lesser propofol concentration affect the balance of the effect of the metabisulfite and the propofol on bronchoconstriction?
In summary, it seems that metabisulfite can modestly reverse propofol's dilation of constricted bronchial muscles, but such reversal requires metabisulfite doses much greater than those used clinically. The metabisulfite effect also may have been overestimated because the ratio of the propofol dose to the metabisulfite dose was half that use in clinical practice. If these observations are correct, do the findings apply to our patients?
Brown RH, Greenberg RS, Wagner EM: Efficacy of propofol to prevent bronchoconstriction: Effects of preservative. A nesthesiology 2001; 94: 851–5Brown, RH Greenberg, RS Wagner, EM
Henkel G: This Month in Anesthesiology: Effects of preservative in propofol. A nesthesiology 2001; 94: 6AHenkel, G
Ashley KD, Herndon DN, Traber LD, Traber DL, Deubel-Ashley K, Stothert JC Jr, Kramer GC: Systemic blood flow to sheep lung: Comparison of flow probes and microspheres. J Appl Physiol 1992; 73: 1996–2003Ashley, KD Herndon, DN Traber, LD Traber, DL Deubel-Ashley, K Stothert, JC Kramer, GC
Ludbrook GL, Upton RN, Grant C, Martinez A: The effect of rate of administration on brain concentrations of propofol in sheep. Anesth Analg 1998; 86: 1301–6Ludbrook, GL Upton, RN Grant, C Martinez, A
Smith C, McEwan AI, Jhaveri R, Wilkinson M, Goodman D, Smith R, Canada AT, Glass PSA: The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. A nesthesiology 1994; 81: 820–8Smith, C McEwan, AI Jhaveri, R Wilkinson, M Goodman, D Smith, R Canada, AT Glass, PSA