Pyruvate Dehydrogenase Activity is Decreased in the Peripheral Blood Mononuclear Cells of Patients with Sepsis: A Prospective Observational Trial

Nuzzo, Erin; Berg, Katherine M.; Andersen, Lars W.; Balkema, Julia; Montissol, Sophia; Cocchi, Michael N.; Liu, Xiaowen; Donnino, Michael W.

doi:10.1513/annalsats.201505-267bc

Cited by 34 publications

(32 citation statements)

References 19 publications

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“…The multiprotein enzyme pyruvate dehydrogenase complex (PDC) is a big, strongly conserved complex that is tightly regulated in activity and is an important sensor of oxygen and a regulator of TCA activity. In sepsis, PDC activity is clearly reduced (Vary, ; Nuzzo et al , ) and several explanations have been provided. PDC needs a co‐factor, thiamin (a.k.a.…”

Section: Sepsis and Mitochondrial Metabolismmentioning

confidence: 99%

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

2018

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Sepsis is a highly lethal and urgent unmet medical need. It is the result of a complex interplay of several pathways, including inflammation, immune activation, hypoxia, and metabolic reprogramming. Specifically, the regulation and the impact of the latter have become better understood in which the highly catabolic status during sepsis and its similarity with starvation responses appear to be essential in the poor prognosis in sepsis. It seems logical that new interventions based on the recognition of new therapeutic targets in the key metabolic pathways should be developed and may have a good chance to penetrate to the bedside. In this review, we concentrate on the pathological changes in metabolism, observed during sepsis, and the presumed underlying mechanisms, with a focus on the level of the organism and the interplay between different organ systems.

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Section: Sepsis and Mitochondrial Metabolismmentioning

confidence: 99%

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

2018

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“…Improved mitochondrial function as evidenced by the increased blood pyruvate after fluid resuscitation compared to at admission levels, may explain the reported decreased BLL and L/P ratio especially in survivors and was found to be significant specific predictor for survival. In support of this assumption, Nuzzo et al [44] found pyruvate dehydrogenase (PDH) activity and quantity in septic patients were significantly lower than in healthy controls and in non-survivor compared to survivors and concluded that PDH activity and quantity are low in sepsis, and this may cause cells to shift to anaerobic metabolism, resulting in increased lactate and decreased pyruvate production.…”

Section: Discussionmentioning

confidence: 98%

Disturbed fluid responsiveness and lactate/pyruvate ratio as predictors for mortality of septic shock patients

Mohamed

Essam

2016

Egyptian Journal of Anaesthesia

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Objectives: Evaluation of fluid responsiveness of septic shock patients admitted to surgical ICU and the predictability of non-invasive monitoring and estimated lactate/pyruvate (L/P) ratio for survival of these patients. Patients and methods: The study included 58 septic shocked patients admitted and managed at surgical ICU. After non-invasive determination of baseline hemodynamic data and calculation of shock index (SI-0) and Pleth variability index (PVI-0), all patients received intravenous colloid infusion followed 15-min later by non-invasive re-evaluation for SI-15 and PVI-15. Blood samples were obtained for estimation of blood lactate and pyruvate levels at admission (BLL-0 and BPL-0) and 12-h after fluid resuscitation (BLL-12 and BPL-12) and L/P ratio was calculated. All patients were managed according to the Surviving Sepsis Campaign guidelines and followed up for ICU mortality rate (MR). Results: ICU stay MR was 20.7%. Survival showed negative significant correlation with PVI, L/P ratio and BLL, while it showed positive significant correlation with BPL. Receiver Operating Characteristic (ROC) curve analysis defined baseline and persistently low PVI, high BLL and L/P ratio as significant sensitive predictors for MR, while elevated BPL-12 as significant specific predictor for survival. Regression analysis defined persistently elevated L/P ratio as the highly significant specific predictor, while persistently disturbed SI and PVI could predict mortality as screening tests. Odds ratio for mortality at BLL-0 of >2 mmol/L was 0.0321 (95% CI: 0.0037-0.2755), while it was 4.1111 (95% CI: 1.0702-15.792) at BLL-0 >4 mmol/L. Conclusion: After fluid resuscitation and hemodynamic stability, persistently elevated BLL could predict mortality, while elevated BPL could predict survival of septic shock patients. Continuous non-invasive evaluation of fluid responsiveness judged by PVI and SI could provide sensitive

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“…8,9 Third, PDH values may be depressed as a direct consequence of critical illness. 10,11 Finally, thiamine is a key cofactor for PDH. Previous studies have shown that thiamine deficiency is common in both type 1 and type 2 diabetes 12,13 and in patients with DKA.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate Dehydrogenase Activity Is Decreased in Emergency Department Patients With Diabetic Ketoacidosis

et al. 2016

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Objectives: The pyruvate dehydrogenase complex (PDH) is an essential enzyme in aerobic metabolism. Ketones are known to inhibit PDH activity, but the extent of this inhibition is unknown in patients with diabetic ketoacidosis (DKA). Methods:We enrolled adult patients presenting to the emergency department in hyperglycemic crisis. Patients were classified as DKA or hyperglycemia without ketoacidosis based on laboratory criteria. Healthy controls were also enrolled. PDH activity and quantity were measured in isolated peripheral blood mononuclear cells. We compared PDH values between groups and measured the relationship of PDH values to measures of acid-base status.Results: Twenty-seven patients (17 with DKA) and 31 controls were enrolled. Patients with DKA had lower PDH activity and quantity compared to the two other groups. PDH activity was significantly correlated with serum bicarbonate and pH and inversely correlated with the anion gap.Conclusions: DKA is associated with greater suppression of PDH activity than hyperglycemia without ketoacidosis, and this is correlated with measures of acid-base status. Future studies may determine whether PDH depression plays a role in the pathophysiology of DKA and whether modification of PDH could decrease time to DKA resolution.ACADEMIC EMERGENCY MEDICINE 2016;23:685-689

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Pyruvate Dehydrogenase Activity is Decreased in the Peripheral Blood Mononuclear Cells of Patients with Sepsis: A Prospective Observational Trial

Cited by 34 publications

References 19 publications

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

Disturbed fluid responsiveness and lactate/pyruvate ratio as predictors for mortality of septic shock patients

Pyruvate Dehydrogenase Activity Is Decreased in Emergency Department Patients With Diabetic Ketoacidosis

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