Table 1 Lack of evidence for the 'traditional' mechanisms explaining sepsis-associated hyperlactatemia

Boekstegers et al.[43]

Muscle PO₂ in septic patients

No evidence of muscle hypoxia

Sair et al.[44]

Levy et al.[45]

VanderMeer et al.[46]

Intestinal and bladder mucosal PO₂ in septic animals

No evidence of mucosal hypoxia

Rosser et al.[47]

Hotchkiss and Karl [48]

Cellular oxygenation by using hypoxic marker ([¹⁸?F] fluoromisonidazole) in septic animals

No cellular hypoxia in muscle, heart, lung and brain

Regueira et al.[49]

Measurements of HIF-1? in septic patients/animals

No relation between HIF-1? and lactate levels

Textoris et al.[50]

Opdam and Bellomo [51]

Lactate production by the lung in septic shock patients

Substantial lactate release by the lung

Mitochondrial dysfunction

Hotchkiss and Karl [48]

Measurements of ATP and PCr in muscle samples of septic animals/patients

No decrease in any of the indicators of mitochondrial function

Alamdari et al.[53]

Brealey et al.[54]

Pyruvate dehydrogenase

Alamdari et al.[53]

Mitochondrial PDH activity in septic animals/patients

No association between PDH deficit/dysfunction and lactate increase

Jahoor et al.[55]

Stacpoole et al.[56]

Dichloroacetate lowers lactate levels by stimulating the PDH complex

DO₂ – VO₂ mismatch

Ronco et al.[57],[58]

Critical DO₂ in septic patients as they approached death

No association between hyperlactatemia and decreased DO₂ or impaired O₂ER

Mira et al.[59]

Relationship between DO₂/SvO₂ and SAHL

No relationship between DO₂/SvO₂ was found

Astiz et al.[60]

Marik and Sibbald [65]

Increases in DO₂ did not decrease lactate concentration in SAHL