Contribution of various metabolites to the “unmeasured” anions in critically ill patients with metabolic acidosis*

Moviat, Miriam; Terpstra, Anniek M.; Ruitenbeek, W.; Kluijtmans, Leo A. J.; Pickkers, Peter; Hoeven, Johannes G. van der

doi:10.1097/ccm.0b013e31816443cb

Cited by 60 publications

(40 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this setting, SIG likely represents unmeasured strong anions. They accumulate in sepsis, renal failure and organ dysfunction, but their origin and chemical nature is only partially understood [14,15]. Increased glycolysis, protein catabolism, mitochondrial dysfunction and decreased clearance likely contribute to their accumulation.…”

Section: Substance Removal and Reversal Of Hypotensionmentioning

confidence: 99%

“…Increased glycolysis, protein catabolism, mitochondrial dysfunction and decreased clearance likely contribute to their accumulation. Potential candidates include sulfate, urate, hydroxybutyrate, succinate, pyroglutamate, D-lactate and Krebs cycle intermediates, but also components of drugs, nutrients or synthetic colloids [15][16][17][18]. However, despite using elaborate techniques to determine the components of SIG, the majority of its determinants are not yet identified [15].…”

Section: Substance Removal and Reversal Of Hypotensionmentioning

confidence: 99%

See 1 more Smart Citation

How to explain and exploit the beneficial effects of high-volume hemofiltration on hemodynamics and strong ion gap

Straaten

Elbers

2013

Intensive Care Med

View full text Add to dashboard Cite

Early high-volume hemofiltration has been suggested as adjuvant treatment for critically ill patients with severe septic shock to stabilize the circulation [1]. Several nonrandomized clinical and animal studies have shown a benefit [2]. The rationale for this treatment is that within the setting of an overwhelming inflammatory response, pro-and antiinflammatory mediators can be removed [3] and homeostasis restored [4]. Grootendorst et al. [5] had already found that substance removal by hemofiltration likely plays a role, because the infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance in normal pigs, while the infusion of ultrafiltrate from healthy pigs does not. However, a recent meta-analysis including randomized controlled trials and subgroups from randomized controlled trials was not able to show any benefit of continuous renal replacement therapy (CRRT) versus no CRRT or a higher dose of CRRT in patients with severe sepsis or septic shock in terms of survival, hemodynamics, pulmonary gas exchange, organ failure and length of stay [6]. The effect of CRRT on survival was not modified by CRRT dose. This was recently confirmed by a large randomized controlled trial [7].Bellomo et al. [8] now specifically report on data from this trial from a nested cohort of 115 patients from two of the participating ICUs. Patients were treated with venovenous hemodiafiltration of either low intensity (with effluent flow at 25 ml/kg/h) or high intensity (at 40 ml/kg/ h). They focused on the control of metabolic acidosis, mean arterial blood pressure and noradrenaline dose and their relationship during the first 24 h of treatment. They found that pH and traditional markers of the metabolic component of acid base balance, i.e. bicarbonate and base excess similarly improved in both groups. However, in the high-intensity arm, lactate and in particular the strong ion gap (SIG) decreased significantly, concomitantly with an increase in mean arterial blood pressure and a decreased noradrenaline dose. These improvements were not observed in the low-intensity arm.These results may be of clinical importance. But how do we explain and more importantly how do we exploit them? Substance removal and reversal of hypotensionHigh-intensity CRRT likely removes more inflammatory mediators than the low-intensity modality. However, the removal of cytokines is often not sufficient to decrease plasma concentrations [9]. The reasons may be the high size and low free fraction of the cytokines, and the higher rate of production compared to removal. In contrast, freecirculating mediators in the middle molecular range, such as complement factors [1], prostaglandins and leukotrienes [10], and myocardial depressant factors [11] are removed [12,13].In the present study, SIG significantly decreased in the high-intensity group, which was not the case in the lowintensity group. This may indicate that substance removal contributed to improved hemodynamics. In this setting, SIG likely represents unmeasured strong anions.

show abstract

Section: Substance Removal and Reversal Of Hypotensionmentioning

confidence: 99%

Section: Substance Removal and Reversal Of Hypotensionmentioning

confidence: 99%

How to explain and exploit the beneficial effects of high-volume hemofiltration on hemodynamics and strong ion gap

Straaten

Elbers

2013

Intensive Care Med

View full text Add to dashboard Cite

show abstract

“…30 Whereas several other studies had demonstrated that delay of academia recovery as opposed to initial pH value was associated with increased mortality in the ICU. 31,32 In our study, we were able to demonstrate that pH was able to predict the risk of death with a RR of 2.94 (CI, 1.14-7.59) In our study we had found that hypoalbuminemia (serum albumin <3.5 g/dl) were present in 101/140 (72%) of all patients and 24/26 (92.3%) of those who had died. Hypoalbuminemia as a predictor of mortality with a RR of 4.8 (95% CI, 1.02 -23.1), PPV 21.8%, NPV 93.3%.…”

Section: 22mentioning

confidence: 66%

Metabolic acidosis in medical intensive care unit with indicators and their prognostic value- A prospective observational study

et al. 2017

View full text Add to dashboard Cite

Background: Metabolic acidosis is a common abnormality in the intensive care unit. There has recently been a surge of interest in nontraditional approaches to the analysis of acid base disorders. Aims and Objectives: This study was undertaken to compare the application of the physicochemical method of Stewart and the traditional Henderson-Hasselbach equation with correction for albumin in quantification of acid base disorders. Materials and Methods: All patients with metabolic acidosis admitted to the ICU as defined by a base deficit of >2.5 were included in the study. The APACHE II score was calculated at admission and the predicted mortality was defined. The acid base disorders were quantified by the traditional approach with anion gap correction for serum albumin as well as by the Stewart method with calculation of the strong anion gap acidosis. Results: One-hundred forty patients were included in the study of which 58% were males. In 125 subjects (89%) acidosis was discovered by the Stewart method. The traditional method detected increased anion gap in 109 subjects (78%) but this increased to 124 (88.5%) when corrected for albumin. Both the strong ion gap (SIG) and the albumin corrected anion gap correlated strongly. Serum lactate levels and SIG predicted mortality as did albumin corrected anion gap. Conclusion: Albumin correction of the anion gap correlates well with acidosis as discovered by the SIG and therefore should be used in the ICUs rather than the traditional anion gap. With this modification, we can thus depend on the application of the intuitive traditional method rather than the more difficult to apply Stewart method for analysis of the acid base abnormalities in the ICU.

show abstract

“…However, this speculation remains to be proven. Other possibilities include increased negatively charged acute phase proteins,36 or exogenous compounds in administered fluids (lactate, acetate, citrate, gluconate)39 or medications (anion‐containing β‐lactam antibiotics, parenteral nutrition)40 administered before hospital admission. However, because the retrospective design of this study we were unable to comment beyond this.…”

Section: Discussionmentioning

confidence: 99%

Physicochemical Approach to Determine the Mechanism for Acid–Base Disorders in 793 Hospitalized Foals

Gómez

Biermann

Sanchez

2015

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundThe quantitative effect of strong electrolytes, unmeasured strong anions (UAs), pCO 2, and plasma protein concentrations in determining plasma pH can be demonstrated using the physicochemical approach. Plasma anion gap (AG) and strong ion gap (SIG) are used to assess UAs in different species.HypothesesStrong ions are a major factor influencing changes in plasma pH of hospitalized foals. AG and SIG accurately predict severe hyper‐l‐lactatemia ([l‐lac−] > 7 mmol/L).AnimalsSeven hundred and ninety three hospitalized foals < 7 days old.MethodsRetrospective study. The relationship between measured pH and physicochemical variables, and the relationship between plasma [l‐lac−] and AG and SIG, were determined using regression analyses. Optimal AG and SIG cut points to predict hyper‐l‐lactatemia were identified using an ROC curve analysis.ResultsCombined, the measured strong ion difference and SIG accounted for 54–69% of the changes in the measured arterial pH of hospitalized foals. AG and SIG were significantly associated with plasma [l‐lac−] (P < .0001). The receiver operator characteristics (ROC) AUC of AG and SIG for prediction of severe hyper‐l‐lactatemia were 0.89 (95%CI, 0.8–0.95; P < .0001) and 0.90 (95%CI, 0.81–0.96; P < .0001), respectively. Severe hyper‐l‐lactatemia was best predicted by AG > 27 mmol/L (sensitivity 80%, 95%CI, 56–94, specificity 85%, 95%CI, 73–93; P < .0001) and SIG <−15 mmol/L (sensitivity 90%, 95%CI, 68–98; specificity 80%; 95%CI, 68–90; P < .0001).Conclusion and clinical relevanceAltered concentrations of strong ions (Na+, K+, Cl−) and UAs were the primary cause of acidemia of hospitalized foals. AG and SIG were good predictors of hyper‐l‐lactatemia and could be used as surrogate tests.

show abstract

Contribution of various metabolites to the “unmeasured” anions in critically ill patients with metabolic acidosis*

Abstract: Amino acids, uric acid, and organic acids together accounted for only 7.9% of the SIG in intensive care unit patients with metabolic acidosis.

Cited by 60 publications

References 24 publications

How to explain and exploit the beneficial effects of high-volume hemofiltration on hemodynamics and strong ion gap

How to explain and exploit the beneficial effects of high-volume hemofiltration on hemodynamics and strong ion gap

Metabolic acidosis in medical intensive care unit with indicators and their prognostic value- A prospective observational study

Physicochemical Approach to Determine the Mechanism for Acid–Base Disorders in 793 Hospitalized Foals

Contact Info

Product

Resources

About