The early phase of critical illness is a progressive acidic state due to unmeasured anions

Antonini, Benvenuto; Piva, Simone; Paltenghi, Massimiliano; Candiani, A; Latronico, Nicola

doi:10.1017/s0265021508003669

Cited by 32 publications

(27 citation statements)

References 21 publications

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“…High (preresuscitation) SIG levels at ICU admission are known to be related to the presence of sepsis, as well as renal and hepatic dysfunction, and are also probably a marker of tissue hypoperfusion [16]. Some studies [17,18] found a clear association between high SIG levels and mortality, whereas one study did not [19]. The prognostic significance of high SIG levels during admission is probably more relevant when preresuscitation values are measured [19].…”

Section: Discussionmentioning

confidence: 99%

An acid-base disorders analysis with the use of the Stewart approach in patients with sepsis treated in an intensive care unit

Szrama¹,

Smuszkiewicz²

2016

Anaesthesiol Intensive Ther

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Background: Patients with sepsis admitted to the intensive care unit often present with acid-base disorders. As the traditional interpretation might be clinically misleading, an alternative approach described by Stewart may allow one to quantify the individual components of acid-base abnormalities and provide an insight into their pathogenesis. The aim of our study was to compare the traditional and Stewart approaches in the analysis of acid-base disturbance. Methods: We analyzed arterial blood gases (ABG) taken from 43 ICU septic patients from admission to discharge categorising them according to SBE values. The traditional concept analysis was compared with the physicochemical approach using the Stewart equations. Results: 990 ABGs were analysed. In the SBE < −2 mEq L -1 group, hyperlactatemia was observed in 34.7% ABG, hypoalbuminemia in 100% and SIG acidosis in 42% ABG. Moreover, a Cl/Na ratio > 0.75 was present in 96.9% ABG. In the normal range SBE group, elevated lactates were present in 21.3% ABG, SIG acidosis in 14.9%, elevated Cl/Na ratio in 98.4% and hypoalbuminemia in all 324 ABG. In the metabolic alkalosis group (SBE > +2 mEq L -1 ), hyperlactatemia was observed in 18.4% ABG, SIG acidosis in 5% ABG, Cl/Na ratio > 0.75 in 88.8%, while 99.1% samples revealed hypoalbuminemia. Conclusion: The use of the Stewart model may improve our understanding of the underlying pathophysiological mechanism and the true etiology of the derangements of acid-base disorders. Indeed, it proves that patients may suffer from mixed arterial blood gas disorders hidden under normal values of SBE and pH.

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Section: Discussionmentioning

confidence: 99%

An acid-base disorders analysis with the use of the Stewart approach in patients with sepsis treated in an intensive care unit

Szrama¹,

Smuszkiewicz²

2016

Anaesthesiol Intensive Ther

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“…As a consequence, a shift to a more acidic pH decreased cystine uptake, whereas the uptake of glutamate, which does not change its ionic state within this pH range, was hardly affected (16,21,137). The regulation of system x c -by pH might be of pathophysiogical relevance, as many disease states, including critical illness (4,44) and diabetes (279), are associated with both acidosis and oxidative stress. Inhibition of system x c -by lactate in rat cortical astrocytes has been reported (124).…”

mentioning

confidence: 99%

The Cystine/Glutamate Antiporter System x_c⁻in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities

Lewerenz

Hewett

Huang

et al. 2013

Antioxidants & Redox Signaling

787

655

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The antiporter system x c -imports the amino acid cystine, the oxidized form of cysteine, into cells with a 1:1 counter-transport of glutamate. It is composed of a light chain, xCT, and a heavy chain, 4F2 heavy chain (4F2hc), and, thus, belongs to the family of heterodimeric amino acid transporters. Cysteine is the rate-limiting substrate for the important antioxidant glutathione (GSH) and, along with cystine, it also forms a key redox couple on its own. Glutamate is a major neurotransmitter in the central nervous system (CNS). By phylogenetic analysis, we show that system x c -is a rather evolutionarily new amino acid transport system. In addition, we summarize the current knowledge regarding the molecular mechanisms that regulate system x c -, including the transcriptional regulation of the xCT light chain, posttranscriptional mechanisms, and pharmacological inhibitors of system x c -. Moreover, the roles of system x c -in regulating GSH levels, the redox state of the extracellular cystine/cysteine redox couple, and extracellular glutamate levels are discussed. In vitro, glutamate-mediated system x c -inhibition leads to neuronal cell death, a paradigm called oxidative glutamate toxicity, which has successfully been used to identify neuroprotective compounds. In vivo, xCT has a rather restricted expression pattern with the highest levels in the CNS and parts of the immune system. System x c -is also present in the eye. Moreover, an elevated expression of xCT has been reported in cancer. We highlight the diverse roles of system x c -in the regulation of the immune response, in various aspects of cancer and in the eye and the CNS. Antioxid. Redox Signal. 18, 522-555.

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“…[14][15][16] In comparison to standard methods, strong ion measurements are able to detect the presence of unmeasured anions, indicating the presence of metabolic acidosis in critically ill patients. 17 Our data show that for severely burn-injured pediatric patients there is a markedly increased SIG, indicating a metabolic acidosis present on admission. Additionally, patients who did not survive had a higher SIG, indicating an increased level of metabolic acidosis.…”

Section: Discussionmentioning

confidence: 59%

Strong Ion Gap is Associated With Mortality in Pediatric Burn Injuries

Sen

Wiktor

Berndtson

et al. 2014

Journal of Burn Care & Research

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Severe burn injury produces significant tissue damage, resulting in metabolic acidosis. Current methods of acid-base evaluation are based on dependent variables that may not be accurate after burn injury. The strong ion method of acid-base evaluation is based on independent variables and may accurately predict outcomes in severely burn-injured patients. The authors hypothesize that an increased strong ion gap present on admission will be associated with mortality in severely burn-injured pediatric patients. A retrospective chart review was performed of burn-injured pediatric patients with a TBSA 20% or greater. Data collected included age, TBSA burn injury, mechanism of injury, survival, ventilator days, hospital length of stay, intensive care unit length of stay, and admission laboratory values. Apparent and effective strong ion difference (SIDa, SIDe) were calculated. The strong ion gap (SIG) was determined as the difference between SIDa and SIDe. A total of 48 patients were included in the study. Mean age (years) and TBSA were 7.9 ± 0.8 years and 56.8 ± 2.6%. Eleven patients (23%) died. Mean TBSA for survivors (54.2 ± 2.9%) did not significantly differ from that of nonsurvivors (65.7 ± 5.34%). Ten patients suffered inhalation injury, which was associated with an odds ratio of 10.1* for mortality. Mean SIDa was 44.2 ± 3.2 for the entire study population. Survivors had a significantly lower SIDa (36.6 ± 0.5) than nonsurvivors (59.7 ± 13*). Mean SIDe for all patients was (25 ± 0.7) and did not differ significantly between survivors (24.7 ± 0.7) and nonsurvivors (25.8 ± 2). SIG for nonsurvivors (33.91 ± 14*) was significantly higher than for survivors (14.9 ± 0.3). Controlling for both TBSA and inhalation injury, death was associated with both an increased SIDa (B = 19.3*) and SIG (B = 17.3*). SIG is increased in severely burn-injured pediatric patients, indicating the presence of metabolic acidosis. Furthermore, an increased SIG is significantly associated with mortality. (*P <.05.).

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The early phase of critical illness is a progressive acidic state due to unmeasured anions

Abstract: Metabolic acidosis by unmeasured anions is a clinically relevant phenomenon, which is correlated with mortality. Progressive metabolic acidosis may be ongoing in the early phase of critical illness despite the absence of acidaemia.

Cited by 32 publications

References 21 publications

An acid-base disorders analysis with the use of the Stewart approach in patients with sepsis treated in an intensive care unit

An acid-base disorders analysis with the use of the Stewart approach in patients with sepsis treated in an intensive care unit

The Cystine/Glutamate Antiporter System x_c⁻in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities

Strong Ion Gap is Associated With Mortality in Pediatric Burn Injuries

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The early phase of critical illness is a progressive acidic state due to unmeasured anions

Abstract: Metabolic acidosis by unmeasured anions is a clinically relevant phenomenon, which is correlated with mortality. Progressive metabolic acidosis may be ongoing in the early phase of critical illness despite the absence of acidaemia.

Cited by 32 publications

References 21 publications

An acid-base disorders analysis with the use of the Stewart approach in patients with sepsis treated in an intensive care unit

An acid-base disorders analysis with the use of the Stewart approach in patients with sepsis treated in an intensive care unit

The Cystine/Glutamate Antiporter System xc−in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities

Strong Ion Gap is Associated With Mortality in Pediatric Burn Injuries

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The Cystine/Glutamate Antiporter System x_c⁻in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities