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Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication.

Protti A, Russo R, Tagliabue P, Vecchio S, Singer M, Rudiger A, Foti G, Rossi A, Mistraletti G, Gattinoni L - Crit Care (2010)

Bottom Line: In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI).Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32).This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Università degli Studi di Milano, Via F, Sforza 35, 20122 Milan, Italy. alessandro.protti@policlinico.mi.it

ABSTRACT

Introduction: Lactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication.

Methods: Multicentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 +/- 0.20; lactate 18 +/- 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available.

Results: On day 1, VO2 was markedly depressed (67 +/- 28 ml/min/m2) despite a normal CI (3.4 +/- 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 +/- 1.0 ml O2/100 ml) or without (2.5 +/- 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32).

Conclusions: VO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia.

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Relation between systemic oxygen consumption and lactatemia in biguanide-intoxicated patients. Systemic oxygen consumption (VO2), computed from either mixed (black circles) or central (white circles) venous oxygen saturation, inversely correlated with plasma lactate (R2 = 0.43; P < 0.001; n = 32).
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Figure 2: Relation between systemic oxygen consumption and lactatemia in biguanide-intoxicated patients. Systemic oxygen consumption (VO2), computed from either mixed (black circles) or central (white circles) venous oxygen saturation, inversely correlated with plasma lactate (R2 = 0.43; P < 0.001; n = 32).

Mentions: Main results are reported in Table 2 and Figures 1 and 2. Systemic O2 consumption, monitored in 11 patients, was abnormally low on day 1 and normalized within the next 48 to 72 hours (P < 0.001), paralleled by resolution of lactic acidosis (P < 0.001). As systemic O2 delivery did not significantly change compared with day 1, variations in whole body O2 consumption were reflected in equal changes in arterio-venous difference in O2 content and O2 extraction index and opposite changes in central venous O2 saturation (P < 0.001 for all). The difference in veno-arterial CO2 content was abnormally low on day 1 and progressively returned to normal (P < 0.05). Whole body CO2 production showed a similar, although not significant, trend, rising from 93 ± 24 (on day 1) to 115 ± 13 ml/min/m2 (on day 4; n = 4). The arterio-venous difference in O2 content was positively associated with the veno-arterial difference in CO2 content (R2 = 0.42; P = 0.001, n = 22). Systemic O2 consumption was positively associated with arterial pH (R2 = 0.37; P < 0.001, n = 32) and body temperature (R2 = 0.38; P < 0.001, n = 30) and inversely correlated with plasma lactate (R2 = 0.43; P < 0.001, n = 32).


Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication.

Protti A, Russo R, Tagliabue P, Vecchio S, Singer M, Rudiger A, Foti G, Rossi A, Mistraletti G, Gattinoni L - Crit Care (2010)

Relation between systemic oxygen consumption and lactatemia in biguanide-intoxicated patients. Systemic oxygen consumption (VO2), computed from either mixed (black circles) or central (white circles) venous oxygen saturation, inversely correlated with plasma lactate (R2 = 0.43; P < 0.001; n = 32).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875537&req=5

Figure 2: Relation between systemic oxygen consumption and lactatemia in biguanide-intoxicated patients. Systemic oxygen consumption (VO2), computed from either mixed (black circles) or central (white circles) venous oxygen saturation, inversely correlated with plasma lactate (R2 = 0.43; P < 0.001; n = 32).
Mentions: Main results are reported in Table 2 and Figures 1 and 2. Systemic O2 consumption, monitored in 11 patients, was abnormally low on day 1 and normalized within the next 48 to 72 hours (P < 0.001), paralleled by resolution of lactic acidosis (P < 0.001). As systemic O2 delivery did not significantly change compared with day 1, variations in whole body O2 consumption were reflected in equal changes in arterio-venous difference in O2 content and O2 extraction index and opposite changes in central venous O2 saturation (P < 0.001 for all). The difference in veno-arterial CO2 content was abnormally low on day 1 and progressively returned to normal (P < 0.05). Whole body CO2 production showed a similar, although not significant, trend, rising from 93 ± 24 (on day 1) to 115 ± 13 ml/min/m2 (on day 4; n = 4). The arterio-venous difference in O2 content was positively associated with the veno-arterial difference in CO2 content (R2 = 0.42; P = 0.001, n = 22). Systemic O2 consumption was positively associated with arterial pH (R2 = 0.37; P < 0.001, n = 32) and body temperature (R2 = 0.38; P < 0.001, n = 30) and inversely correlated with plasma lactate (R2 = 0.43; P < 0.001, n = 32).

Bottom Line: In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI).Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32).This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Università degli Studi di Milano, Via F, Sforza 35, 20122 Milan, Italy. alessandro.protti@policlinico.mi.it

ABSTRACT

Introduction: Lactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication.

Methods: Multicentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 +/- 0.20; lactate 18 +/- 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available.

Results: On day 1, VO2 was markedly depressed (67 +/- 28 ml/min/m2) despite a normal CI (3.4 +/- 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 +/- 1.0 ml O2/100 ml) or without (2.5 +/- 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32).

Conclusions: VO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia.

Show MeSH
Related in: MedlinePlus