Temporal changes in whole-blood and plasma glutathione in ICU patients with multiple organ failure

Fläring, Urban; Rooyackers, Olav; Hebert, Christina; Bratel, T.; Hammarqvist, Folke; Wernerman, Jan

doi:10.1007/s00134-005-2687-0

Cited by 35 publications

(35 citation statements)

References 19 publications

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“…Glutamine is also important for the synthesis of the amino acid citrulline which is exclusively synthesized in the gut and is suggested to be a useful indicator of enteral tolerance in children with short bowel syndrome (Rhoads et al 2005). Furthermore, glutamine is a precursor for glutathione, (Flaring et al 2003a) which is the quantitatively most important scavenger of reactive oxygen species (ROS), and produced at increasing rates during critical illness (Alonso de Vega et al 2002;Flaring et al 2003bFlaring et al , 2005. Plasma glutamine concentration can be restored to normal levels by supplementing the patients with intravenous glutamine (Tjader et al 2004).…”

Section: Introductionmentioning

confidence: 97%

Plasma glutamine deficiency is associated with multiple organ failure in critically ill children

et al. 2014

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A low plasma glutamine concentration (<420 µmol/L) is an independent risk factor for mortality in critically ill adult patients. Glutamine metabolism in children is less well characterized. However, pediatric ICU (PICU) mortality is low and, therefore, mortality is difficult to use as an endpoint. Here we evaluated if plasma glutamine concentration at admission to the PICU, relates to the development of multiple organ failure, using pediatric logistic organ dysfunction score (PELOD)-score. In this observational study, consecutive critically ill children (n = 149) admitted to the PICU of a tertiary university hospital as well as a reference group of healthy children (n = 60) were included. Plasma glutamine concentration and the PELOD were determined at admission for all patients and at day 5 for those patients still in the PICU. Plasma glutamine concentration at admission was low in the PICU patients as compared to controls (p = 0.00002) and patients with a low plasma glutamine concentration had more organ failure as compared to patients with higher plasma glutamine concentration (p = 0.0001). Plasma glutamine concentration normalized in patients staying >5 days in the PICU. Plasma glutamine depletion was present in 40 % of patients at PICU admission and it was associated with the development of multiple organ failure. Furthermore, the majority of the critically ill children normalized their plasma glutamine concentration within 5 days, which is different from adult ICU patients. The study suggests that an initial plasma glutamine deficiency is associated with multiple organ failure in critically ill children.

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Section: Introductionmentioning

confidence: 97%

Plasma glutamine deficiency is associated with multiple organ failure in critically ill children

et al. 2014

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“…Contributory factors include malnutrition [9], pregnancy [9], liver disease [10], female gender [11], and alcohol abuse [12]. There is also some evidence that glutathione levels may be decreased in critical illness and in sepsis [13,14].…”

Section: Discussionmentioning

confidence: 99%

“…The association between paracetamol intake, elevated 5-oxoproline levels and a raised anion gap metabolic acidosis has been highlighted in case reports however the incidence of metabolic acidosis caused by excess 5-oxoproline is unknown. It is important to be aware that ICU patients may have several risk factors for depletion of glutathione stores and in fact that critical ilness [13] and sepsis [14] may themselves be associated with reduced glutathione. We suspect that this may be an underrecognized cause for metabolic acidosis in the ICU and we would agree with the suggestion that 5-oxoproline excess should be routinely considered in the differential diagnosis for a cause for a metabolic acidosis [17].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Acidosis with a Raised Anion Gap Associated with High 5-Oxoproline Levels; An Under-Recognized Cause for Metabolic Acidosis in Intensive Care

M¹

2014

J Clin Toxicol

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Metabolic acidosis is a common problem in ICU patients. Frequent causes of metabolic acidosis with a raised anion gap include lactic acidosis and ketoacidosis. In recent years high anion gap acidosis due to acquired 5-oxoprolinuria has been reported in association with chronic paracetamol use 1. There have been occasional reports of acidosis due to 5-oxoproline in an ICU setting 2 but to date there does not seem to be a general awareness of this phenomonen. 5-oxoproline is an amino acid derivative within the γ-glutamyl cycle within the liver, When gluathione stores are depleted γ-glutamycycteine synthase activity increases in an attempt to replenish the glutathione stores. However in the process excess glutamylcycteine is produced which is then converted into 5-oxoproline which can accumulate and cause a metabolic acidosis.We present a case series of unexplained high anion gap metabolic acidoses in ICU associated with an acculumation of 5-oxoproline. These patients had a background history of alcohol abuse and/or malnutrition and had received paracetamol 4 g/day over periods of 2-3 weeks in ICU. Urinary 5-oxoproline levels were tested and were found to be abnormally high. In all these cases cessation of the paracetamol resulted in correction of the acidosis. It is likely that a combination of predisposing factors and prolonged paracetamol treatment resulted in depletion of glutathione stores in these patients.ICU patients may have risk factors for depletion of glutathione stores. Prolonged use of paracetamol in these patients can further deplete gluathione and introduce the risk of developing metabolic acidosis due to 5-oxoproline.

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“…Catabolic illnesses are commonly associated with oxidative stress and decreased antioxidant capacity [15,21,[36][37][38]. Gln supplementation has been shown to improve tissue and blood GSH concentration in animal models of critical illness, possibly by serving as a precursor to glutamate, a constituent of the tripeptide GSH [35].…”

Section: Discussionmentioning

confidence: 99%

Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: A pilot study

et al. 2008

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Temporal changes in whole-blood and plasma glutathione in ICU patients with multiple organ failure

Abstract: This study demonstrates that glutathione remains depleted in whole blood. This contrasts to what has previously been shown in skeletal muscle where a restitution of glutathione concentration is seen.

Cited by 35 publications

References 19 publications

Plasma glutamine deficiency is associated with multiple organ failure in critically ill children

Plasma glutamine deficiency is associated with multiple organ failure in critically ill children

Metabolic Acidosis with a Raised Anion Gap Associated with High 5-Oxoproline Levels; An Under-Recognized Cause for Metabolic Acidosis in Intensive Care

Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: A pilot study

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