• Adult
• Blood Transfusion/statistics & numerical data
• Female
• Hemorrhage/therapy
• Humans
• Infections/etiology
• Injury Severity Score
• Male
• Risk Factors
• Wounds and Injuries/surgery

• R01 HL119248 NHLBI NIH HHS

• Henderson–Hasselbalch
• Stewart
• anion gap
• strong ion difference
• strong ion gap

• Anion gap
• Base excess
• Metabolic acidosis
• Strong ion difference
• Strong ion gap
• Unmeasured anions

• Acid-base balance
• Base replacement
• Fluid therapy
• Metabolic acidosis
• Physiology

• Acid-Base Equilibrium/drug effects
• Acidosis/veterinary
• Animals
• Crystalloid Solutions
• Fluid Therapy/veterinary
• Hydrogen-Ion Concentration
• Infusions, Intravenous/veterinary
• Isotonic Solutions/administration & dosage
• Isotonic Solutions/pharmacology

Corrected anion gap and strong ion gap are commonly used to estimate unmeasured anions. We evaluated the performance of the anion gap corrected for albumin, phosphate and lactate in predicting strong ion gap in a mixed population of critically ill patients. We hypothesized that anion gap corrected for albumin, phosphate and lactate would be a good predictor of strong ion gap, independent of the presence of metabolic acidosis. In addition, we evaluated the impact of strong ion gap at admission on hospital mortality.

We included 84 critically ill patients. Correlation and agreement between the anion gap corrected for albumin, phosphate and lactate and strong ion gap was evaluated by the Pearson correlation test, linear regression, a Bland-Altman plot and calculating interclass correlation coefficient. Two subgroup analyses were performed: one in patients with base-excess <-2mEq/L (low BE group - lBE) and the other in patients with base-excess >-2mEq/L (high BE group - hBE). A logistic regression was performed to evaluate the association between admission strong ion gap levels and hospital mortality.

There was a very strong correlation and a good agreement between anion gap corrected for albumin, phosphate and lactate and strong ion gap in the general population (r²=0.94; bias 1.40; limits of agreement -0.75 to 3.57). Correlation was also high in the lBE group (r²=0.94) and in the hBE group (r²=0.92). High levels of strong ion gap were present in 66% of the whole population and 42% of the cases in the hBE group. Strong ion gap was not associated with hospital mortality by logistic regression.

Anion gap corrected for albumin, phosphate and lactate and strong ion gap have an excellent correlation. Unmeasured anions are frequently elevated in critically ill patients with normal base-excess. However, there was no association between unmeasured anions and hospital mortality.

The Stewart approach-the application of basic physical-chemical principles of aqueous solutions to blood-is an appealing method for analyzing acid-base disorders. These principles mainly dictate that pH is determined by three independent variables, which change primarily and independently of one other. In blood plasma in vivo these variables are: (1) the PCO₂; (2) the strong ion difference (SID)-the difference between the sums of all the strong (i.e., fully dissociated, chemically nonreacting) cations and all the strong anions; and (3) the nonvolatile weak acids (A_tot). Accordingly, the pH and the bicarbonate levels (dependent variables) are only altered when one or more of the independent variables change. Moreover, the source of H⁺ is the dissociation of water to maintain electroneutrality when the independent variables are modified. The basic principles of the Stewart approach in blood, however, have been challenged in different ways. First, the presumed independent variables are actually interdependent as occurs in situations such as: (1) the Hamburger effect (a chloride shift when CO₂ is added to venous blood from the tissues); (2) the loss of Donnan equilibrium (a chloride shift from the interstitium to the intravascular compartment to balance the decrease of A_tot secondary to capillary leak; and (3) the compensatory response to a primary disturbance in either independent variable. Second, the concept of water dissociation in response to changes in SID is controversial and lacks experimental evidence. In addition, the Stewart approach is not better than the conventional method for understanding acid-base disorders such as hyperchloremic metabolic acidosis secondary to a chloride-rich-fluid load. Finally, several attempts were performed to demonstrate the clinical superiority of the Stewart approach. These studies, however, have severe methodological drawbacks. In contrast, the largest study on this issue indicated the interchangeability of the Stewart and conventional methods. Although the introduction of the Stewart approach was a new insight into acid-base physiology, the method has not significantly improved our ability to understand, diagnose, and treat acid-base alterations in critically ill patients.

• Acid-base metabolism
• Stewart approach
• Base excess
• Bicarbonate
• Anion gap
• Strong ion difference
• Strong ion gap

There is a complex interplay between changes in acid–base components and inflammation. This manuscript aims to explore associations between plasma cytokines and chemokines and acid–base status on admission to intensive care.

We conducted a prospective cohort study in a 13-bed ICU in a tertiary-care center in Brazil. 87 unselected patients admitted to the ICU during a 2-year period were included. We measured multiple inflammatory mediators in plasma using multiplex assays and evaluated the association between mediator concentrations and acid–base variables using a variety of statistical modeling approaches, including generalized linear models, multiadaptive regression splines and principal component analysis.

We found a positive association between strong ion gap (SIG) and plasma concentrations of interleukin (IL)6, 8, 10 and tumor necrosis factor (TNF); whereas albumin was negatively associated with IL6, IL7, IL8, IL10, TNF and interferon (IFN)α. Apparent strong ion difference (SID_a) was negatively associated with IL10 and IL17. A principal component analysis including SAPS 3 indicated that the association between acid–base components and inflammatory status was largely independent of illness severity, with both increased SIG and decreased SID_a (both drivers of acidosis) associated with increased inflammation.

Acid–base variables (especially increased SIG, decreased albumin and decreased SID_a) on admission to ICU are associated with immunological activation. These findings should encourage new research into the effects of acid–base status on inflammation.

In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses.

We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed.

Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate.

The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population.