Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury

Holbein, Monika; Béchir, Markus; Ludwig, Sabine; Sommerfeld, Jutta; Cottini, Silvia R; Keel, Marius; Stocker, Reto; Stover, John

doi:10.1186/cc7711

Cited by 42 publications

(26 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Third, peripheral hyperglycemia, especially in the presence of increased glucose metabolism or even pathological hyperglycolysis due to nonischemic failure of the TCA cycle, can contribute to acidosis with accumulation of lactate and P bt CO 2 , a finding well described previously. [29][30][31] Relatively high extracellular glucose levels, considering that metabolism is likely to be increased, may support this explanation, although without data on arterial glucose values it remains only a theoretical possibility.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Brain Ph with or without Hypoxia is a Marker of Profound Metabolic Derangement and Increased Mortality after Traumatic Brain Injury

Timofeev

Nortje

Al-Rawi

et al. 2012

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Cerebral hypoxia and acidosis can follow traumatic brain injury (TBI) and are associated with increased mortality. This study aimed to evaluate a relationship between reduced pH bt and disturbances of cerebral metabolism. Prospective data from 56 patients with TBI, receiving microdialysis and Neurotrend monitoring, were analyzed. Four tissue states were defined based on pH bt and P bt O 2 : 1-low P bt O 2 /pH bt , 2-low pH bt /normal P bt O 2 , 3-normal pH bt /low P bt O 2 , and 4-normal pH bt /P bt O 2 ). Microdialysis values were compared between the groups. The relationship between P bt O 2 and lactate/pyruvate (LP) ratio was evaluated at different pH bt levels. Proportional contribution of each state was evaluated against mortality. As compared with the state 4, the state 3 was not different, the state 2 exhibited higher levels of lactate, LP, and glucose and the state 1-higher LP and reduced glucose (Po0.001). A significant negative correlation between LP and P bt O 2 (rho ¼ À 0.159, Po0.001) was stronger at low pH bt (rho ¼ À 0.201, Po0.001) and nonsignificant at normal pH bt (P ¼ 0.993). The state 2 was a significant discriminator of mortality categories (P ¼ 0.031). Decreased pH bt is associated with impaired metabolism. Measuring pH bt with P bt O 2 is a more robust way of detecting metabolic derangements.

show abstract

Section: Discussionmentioning

confidence: 99%

Extracellular Brain Ph with or without Hypoxia is a Marker of Profound Metabolic Derangement and Increased Mortality after Traumatic Brain Injury

Timofeev

Nortje

Al-Rawi

et al. 2012

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…An elevated CMR O2 /CMR glc ratio appears to be unusual after TBI, and the ratio 46 was not because of blood lactate consumption in the Holbein study 95 because there was a concomitant increase in net lactate release from brain when arterial glucose levels were lowest and ratio highest. These subjects probably had cerebral hypoglycemia, and endogenous metabolites oxidized during hypoglycemia include glycogen, glycolytic and tricarboxylic acid cycle intermediates, and amino acids (e.g., glutamine, glutamate, GABA, alanine).…”

Section: Some Speculations: Hypoglycemic Glycogenolysis Mitochondriamentioning

confidence: 99%

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

Dienel

2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as 'preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte-neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted.

show abstract

“…2 Mechanisms of brain injury from hyperglycemia Experimental animal data and human studies provide evidence that even mild hypoglycemia can induce neuroglycopenia and cerebral metabolic distress. Studies of cerebral metabolism using jugular venous measurements (i.e., arteriovenous oxygen and glucose consumption) [59] and cerebral microdialysis (i.e., brain tissue glucose and lactate/pyruvate ratio) [24,26,60] indicate that serum glucose levels below 108 mg/dl (6 mmol/l) are associated with neuroglycopenia and metabolic distress in patients with severe TBI. Although studies using a combination of microdialysis and [ 18 F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (PET) suggest that severe TBI patients may initially develop increased glucose utilization without necessarily shifting toward anaerobic metabolism [38], this state of hyperglycolysis [39] can subsequently predispose patients to develop metabolic crisis if the glucose supply becomes inadequate.…”

Section: The Perils Of Hypoglycemia For the Acutely Injured Brainmentioning

confidence: 99%

Treating Hyperglycemia in Neurocritical Patients: Benefits and Perils

Godoy

Napoli²,

Rabinstein

2010

Neurocrit Care

View full text Add to dashboard Cite

There is growing debate over the value of intensive insulin therapy (IIT) in critically ill patients. Available trials have been performed in general medical or surgical intensive care units, and the results may not be directly applicable to patients with severe acute brain disease because these patients may have heightened susceptibility to hyperglycemia (HyperG) and hypoglycemia. Our objective was to review the pathophysiology and effects of HyperG and hypoglycemia in neurocritical patients and to analyze the potential role of IIT in this population. Source data were obtained from a PubMed search of the medical literature combining the terms HyperG, hypoglycemia, insulin, stroke, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), spinal cord injury (SCI), and related diagnoses. Brain metabolism is highly dependent on constant supply of glucose. As a consequence, the acutely injured brain is particularly sensitive to hypoglycemia, which can induce a state of energy failure (metabolic crisis). Meanwhile, neurocritical patients have a high prevalence of HyperG, and its occurrence is associated with poor outcome after acute ischemic stroke, ICH, SAH, and TBI. It is unclear whether this association is due to direct detrimental effects exerted by HyperG or simply represents a marker of severe brain injury. Insulin has been shown to have various potentially pleiotropic neuroprotective properties in experimental models. However, the safety and efficacy of IIT in patients with critical brain disease have not been well studied. Available results do not support the use of IIT to maintain strict normoglycemia in this population. Patients with critical brain disease should have frequent glucose monitoring because severe HyperG and even modest hypoglycemia may be detrimental. Careful use of insulin infusion protocols appears advisable, but maintenance of strict normoglycemia cannot be recommended. Rigorous studies must be conducted to assess the value of insulin therapy and to determine the optimal blood glucose targets in patients with the most common acute vascular and traumatic brain insults.

show abstract

Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury

Abstract: Introduction Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined.

Cited by 42 publications

References 61 publications

Extracellular Brain Ph with or without Hypoxia is a Marker of Profound Metabolic Derangement and Increased Mortality after Traumatic Brain Injury

Extracellular Brain Ph with or without Hypoxia is a Marker of Profound Metabolic Derangement and Increased Mortality after Traumatic Brain Injury

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

Treating Hyperglycemia in Neurocritical Patients: Benefits and Perils

Contact Info

Product

Resources

About