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Another explanation for decreased oxygen consumption in lactic acidosis

Critical Care201014:427

https://doi.org/10.1186/cc9072

  • Published:

Keywords

  • Lactic Acid
  • Metformin
  • Oxygen Consumption
  • Lactic Acidosis
  • Oxygen Delivery

In their recent paper, Protti and colleagues reported depressed oxygen consumption in patients with lactic acidosis due to biguanide intoxication and they suppose that the cause is inhibited mitochondrial respiration [1].

Another explanation for depressed oxygen consumption in these patients is also possible, however. If the blood pH is very low, glucose utilization is decreased [2] because the glycolytic enzyme phosphofructokinase is pH dependent - with decreasing pH, its activity is also decreasing [3]. Glucose utilization is an oxygen-consuming process:

The consequence of decreased utilization of glucose is thus also decreased oxygen consumption.

The patients reported by Protti and colleagues had on admission very low blood pH of 6.93 ± 0.20 and systemic oxygen consumption of 67 ± 28 ml/min/m2 [1]. Systemic oxygen consumption 'normalized within the next 48-72 hours' and 'Systemic O2 consumption was positively associated with arterial pH' (P < 0.001). According to Tables 2 and 3 [1], arterial pH reached normal values on days 2 to 3.

Depressed oxygen consumption in patients reported by Protti and colleagues can thus be explained by their very low blood pH.

Authors' response

Alessandro Protti and Luciano Gattinoni

We thank Dr Rosival for his stimulating comment.

Whether acidosis has an impact on oxygen consumption (VO2) remains unclear. In vitro, several studies have demonstrated that tissue VO2 only starts to diminish when the pH falls below 6 to 6.5 [4, 5]. In vivo, both animal and clinical studies have reported normal, or even increased, whole-body VO2 during severe acidosis [6, 7]. Accordingly, we have observed no correlation between VO2 and arterial pH among 762 critically ill patients, at the time of admission to intensive care (R2 = 0.00, P = 0.88 on linear regression analysis) [8].

In order to directly address the issue raised by Dr Rosival, we equipped two healthy, sedated and mechanically ventilated pigs with a metabolic module (to record VO2) and a pulmonary artery catheter (to compute the global oxygen delivery). Following baseline recordings, one animal received a continuous intravenous infusion of metformin whereas the other received lactic acid. Arterial pH, VO2 and oxygen delivery were recorded hourly for 10 hours. As shown in Figure 1, metformin progressively decreased VO2 but lactic acid did not. Changes in oxygen delivery were always minor.
Figure 1
Figure 1

Effect of metformin and lactic acid on arterial pH and oxygen consumption. Upper panel: data recorded from a pig infused with 8 g metformin (final serum drug concentration, 98 μg/ml). Lower panel: data recorded from a pig infused with lactic acid. Lactatemia equally increased from 1 to 25 mmol/l in the two animals. VO2, oxygen consumption.

We are thus tempted to believe that drug toxicity, rather than acidosis, was the major factor responsible for the decrease in VO2 we observed in patients with biguanide-induced lactic acidosis.

Abbreviations

VO2

oxygen consumption.

Declarations

Authors’ Affiliations

(1)
SYNLAB Department of Laboratory Medicine, Dérer'sHospital, Limbová 5, Bratislava, SK-8333 05, Slovakia

References

  1. Protti A, Russo R, Tagliabue P, Vecchio S, Singer M, Rudiger A, Foti G, Rossi A, Mistraletti G, Gattinoni L: Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication. Crit Care 2010, 14: R22. 10.1186/cc8885PubMed CentralView ArticlePubMedGoogle Scholar
  2. Van Nimmen D, Weyne J, Demeester G, Leusen I: Local cerebral glucose utilization in systemic acidosis. Am J Physiol 1984, 247: R639-R645.PubMedGoogle Scholar
  3. Trivedi B, Danforth WH: Effect of pH on the kinetics of frog muscle phosphofructokinase. J Biol Chem 1966, 241: 4110-4112.PubMedGoogle Scholar
  4. Koehler AE, Reitzel RJ: The effect of pH on the oxygen consumption of tissues. J Biol Chem 1925, 64: 739-751.Google Scholar
  5. Canzanelli A, Greenblatt M, Rogers GA, Rapport D: The effect of pH on the in-vitro O 2 consumption of tissues. Am J Physiol 1939, 127: 290-295.Google Scholar
  6. Nahas GG, Ligou JC, Mehlman B: Effects of pH changes on O 2 uptake and plasma catecholamine levels in the dog. Am J Physiol 1960, 198: 60-66.PubMedGoogle Scholar
  7. Fisher P, Kleinerman JI: Total oxygen consumption and metabolic rate of patients with diabetic acidosis. J Clin Invest 1952, 31: 126-130. 10.1172/JCI102571PubMed CentralView ArticlePubMedGoogle Scholar
  8. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R: A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO 2 Collaborative Group. N Engl J Med 1995, 333: 1025-1032. 10.1056/NEJM199510193331601View ArticlePubMedGoogle Scholar

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© BioMed Central Ltd 2010

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