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Cerebral blood flow and oxidative metabolism during human endotoxaemia

Background and purpose

In a model of human endotoxaemia, we have previously shown that the blood concentration of tumour necrosis factor alpha (TNF-a) peaks at 90 min after an intravenous bolus of endotoxin (ETX) [1]. At this time (peak TNF-a), subjective symptoms are marked. We measured cerebral blood flow (CBF) and cerebral metabolic rates (CMR) of oxygen (O2), glucose (glu), and lactate (lac), at peak TNF-a after ETX.

Subjects and methods

Eight healthy young volunteers (median age, 25 [range, 21-28] years) were studied. Informed consent was obtained after approval by subjects and the Scientific-Ethics Committee of Copenhagen. After an overnight fast, catheters were placed in the left radial artery, the right internal jugular bulb, and bilaterally in the antecubital veins. Isotonic glucose was infused at 100 ml/hour. Mean arterial pressure (MAP), heart rate, peripheral saturation, and rectal temperature (Tprect) were continuously monitored. CBF and CMR were measured by the Kety-Schmidt technique [2] at baseline, during normoventilation and voluntary hyperventilation (to measure subject-specific CO2 reactivity), and 90 min after an intravenous bolus (2 ng/kg) of a standard E. coli endotoxin (ETX).


At 90 min, Tprect was slightly, but significantly increased from baseline (median 37.0 [range, 36.6-37.3] vs 37.6 [37.0-38.5]°C); MAP was unchanged (96 [74-107] vs 99 [72-126] mmHg). Subjective symptoms were headache, nausea, chills, and shivering but not overt encephalopathy. Compared to baseline, CBF was significantly decreased; however, PaCO2 also decreased, and the CBF decrease was sufficiently explained by hyperventilation, as calculated from individual CO2 reactivities. A trend occurred towards decreased CMRlac, ie increased lactate efflux, similarly explained by hyperventilation. CMRO2 remained unchanged after ETX, whereas we observed a trend towards decreased CMRgluassociated with decreasing blood glucose levels. All subjects were alert without signs of cerebral dysfunction throughout the study.


In this human model of early sepsis, the high levels of TNF-a were associated with spontaneous hyperventilation, which decreased CBF and increased cerebral lactate efflux, but did not affect the cerebral metabolic rate of oxygen. Thus, high circulating levels of TNF-a during endotoxaemia and sepsis appear not to be responsible for the development of encephalopathy by a direct reduction in global cerebral oxidative metabolism.


  1. 1.

    Krabbe K, et al: Clin Diagn Lab Immunol. 2001 (in press)

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  2. 2.

    Kety SS, Schmidt CF: J Clin Invest. 1948, 27: 476-483.

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Møller, K., Strauss, G., Qvist, J. et al. Cerebral blood flow and oxidative metabolism during human endotoxaemia. Crit Care 5, P179 (2001).

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  • Cerebral Blood Flow
  • Mean Arterial Pressure
  • Tumour Necrosis Factor Alpha
  • Jugular Bulb
  • Cerebral Metabolic Rate