Changes In Base Excess Research Articles

Exploring dynamic change in arterial base excess with patient outcome and lactate clearance in the intensive care unit by hierarchical time-series clustering.

Hyperlactatemia is common in the intensive care unit (ICU) and relevant to prognosis, while the process of lactate normalization requires a relatively long period. We hypothesized that the dynamic change in base excess (BE) would be associated with ICU mortality and lactate clearance. We performed a retrospective cohort study of adult patients with hyperlactatemia admitted to the ICU from 2016 to 2021. The patients were divided into two groups according to whether the peak BE in 12 h was reached in the first 6 h. We compared ICU mortality and lactate clearance at 6 and 12 h after ICU admission. During the study period, 1,608 patients were admitted to the ICU with a lactate concentration of >2.0 mmol/L and stayed in the ICU for >24 h. The mortality rate was 11.2%. The patients were divided into two groups according to whether the peak BE was reached in the first 6 h following ICU admission: Peak BE12h ≤ 6h and Peak BE12h > 6h. The patients were also recorded as whether bicarbonate treatment was received (bicarbonate group, CRRT included) or not (non-bicarbonate group). Furthermore, lactic acid clearance patterns were identified by time-series clustering (TSC) using various algorithms and distance measures. We compared ICU mortality and lactate clearance at 6 and 12 h after ICU admission with logistic regression. After adjustment for other confounding factors, we found that Peak BE12h > 6h was independently associated with ICU mortality with an odds ratio of 2.231 (p = 0.036) in the bicarbonate group and 2.359 (p < 0.005) in the non-bicarbonate group. In addition, based on the definition of >10% lactate clearance at 6 h or >30% at 12 h, we found that Peak BE12h ≤ 6h had 85.2% sensitivity and 38.1% specificity for effective lactate clearance. In time-series clustering analysis, four categories were discriminated, and pattern of lactic acid clearance reveals the early prognostic value of BE in clearance of lactic acid. A prolonged time to reaching the peak BE was independently associated with ICU mortality. In patients with hyperlactatemia, Peak BE12h ≤ 6h could be used as an indicator to predict effective lactate clearance.

Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial.

To determine whether treatment with Plasmalyte-148 (PL) compared to sodium chloride 0.9% (SC) results in faster resolution of diabetic ketoacidosis (DKA) and whether the acetate in PL potentiates ketosis. We conducted a cluster, crossover, open-label, randomized, controlled Phase 2 trial at seven hospitals in adults admitted to intensive care unit (ICU) with severe DKA with hospital randomised to PL or SC as fluid therapy. The primary outcome, DKA resolution, was defined as a change in base excess to ≥ - 3mEq/L at 48h. Ninety-three patients were enrolled with 90 patients included in the modified-intention-to-treat population (PL n = 48, SC n = 42). At 48h, mean fluid administration was 6798 ± 4850ml vs 6574 ± 3123ml, median anion gap 6mEq/L (IQR 5-7) vs 7mEq/L (IQR 5-7) and median blood ketones 0.3mmol/L (IQR 0.1-0.5) vs 0.3 (IQR 0.1-0.5) in the PL and SC groups. DKA resolution at 48h occurred in 96% (PL) and 86% (SC) of patients; odds ratio 3.93 (95% CI 0.73-21.16, p = 0.111). At 24h, DKA resolution occurred in 69% (PL) and 36% (SC) of patients; odds ratio 4.24 (95% CI 1.68-10.72, p = 0.002). The median ICU and hospital lengths of stay were 49h (IQR 23-72) vs 55h (IQR 41-80) and 81h (IQR 58-137) vs 98h (IQR 65-195) in the PL and SC groups. Plasmalyte-148, compared to sodium chloride 0.9%, may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis. These findings need confirmation in a large, Phase 3 trial.

Base excess and pH as predictors of outcomes in secondary peritonitis in a resource limited setting - A prospective study

Background: Estimation of the serum pH and base excess as determinants of the adequacy of resuscitation may predict the patient outcome in peritonitis. Materials, Patients and Methods: This was a prospective study conducted in University College Hospital, Ibadan, on patients from 18 years and above with diagnosis of secondary peritonitis who had exploratory laparotomy over a 4-month period (January to April 2017). The patients' biodata, pulse rate, blood pressure, and clinical diagnosis were documented. At presentation, the patients were resuscitated with intravenous normal saline and broad-spectrum antibiotics. Each patient had measurements of acid-base status, and pH analyzed at presentation and in the immediate postoperative period (within 1 h) using the I-STAT point of care device. They were followed up for 48 h after the surgery. The changes in base excess and serum pH in survivors and nonsurvivors were described at 48 h after surgery. This was statistically compared using SPSS version 20 (Chicago, IL, USA). Results: A total of 45 patients were recruited comprising 37 males and 8 female patients. The mean age was 40.86 ± 15.45 years. The mean admission base excess was −4.76 ± 5.41. The mean admission pH was 7.41 ± 0.07. There were 28 (62%) survivors and 17 (38%) mortalities. The pH on admission and base excess values and after surgery demonstrated statistical significance in survivors and nonsurvivors. Conclusion: Changes in base excess and serum pH values are plausible outcome markers in patients with peritonitis resuscitated with early goal-directed therapy.

Hemodynamic Changes Following Routine Fluid Resuscitation in Patients With Blunt Trauma.

BackgroundThe management of trauma patients is often difficult. The American college of surgeons suggests using advanced trauma life support (ATLS) measures. ATLS is regarded as the gold standard for the resuscitation of cases with acute life threatening injuries.ObjectivesTo assess the change in base excess (BE) values and central venous pressure (CVP) one and six hours after injection of 1000 cc normal saline in trauma patients admitted to the ICU.Patients and MethodsAccording to the inclusion and exclusion criteria, patients were randomly selected to participate in the project. Inclusion criteria included trauma patients admitted to the ICU with a CVP line and who had indication for hydration. In trauma patients, at the zero time period, BP, PR, RR and CVP were measured, and a blood gas test was used to assess Hb, pH, BE, PO2, HCO3 and PCO2. Then 1000 cc of normal saline was injected, and after one and six hours, the same values were re-evaluated.ResultsThe mean age of the patients was 38.1 ± 3.9 (range 15 - 60). The mean duration of hospitalization was 7.4 ± 4.4 (range 1 - 21) days. The mean ISS for these patients was 14.33 ± 5.3. BE changes in both groups of patients, based on Hb primary division, showed a significant difference (P ≤ 0.05). The results showed that there was no significant relation between the measured ISS and the changes in base values (P ≥ 0.05).ConclusionsAccording to our results, the infusion of one liter normal saline will cause a statistically significant decrease only in BD, after one hour, in patients with moderate to severe ISS. The changes in SBP, PR, CVP and also pH, HCO3 and Hb were not statistically remarkable.

A systematic review of human and veterinary applications of noninvasive tissue oxygen monitoring.

To describe the methodology for and utilization of tissue oxygen monitoring by near infrared spectroscopy, and to review the current literature on the use of this monitoring modality in human and veterinary settings. Scientific reviews and original research found using the PubMed and CAB Abstract search engines with the following keywords: "tissue oxygen monitoring," "near-infrared tissue spectroscopy," and "tissue oxygen saturation (StO2 )." Tissue oxygen monitors have been evaluated in a wide variety of human clinical applications including trauma and triage, surgery, sepsis, and septic shock, and early goal-directed therapy. StO2 more rapidly identifies occult shock in human patients compared to traditional methods, which can lead to earlier intervention in these patients. Veterinary studies involving tissue oxygen monitoring are limited, but the technology may have utility for identification of hemorrhagic shock earlier than changes in base excess, blood lactate concentration, or other traditional perfusion parameters. Tissue oxygen monitoring is most commonly performed utilizing a noninvasive, portable monitor, which provides real-time, continuous, repeatable StO2 measurements. A decline in StO2 is an early indicator of shock in both human and veterinary patients. Low StO2 values in human patients are associated with increased morbidity, mortality, and length of hospitalization, as well as the development of multiple organ system dysfunction and surgical site infections.

The Effect of Blood Loss in the Presence and Absence of Severe Soft Tissue Injury on Hemodynamic and Metabolic Parameters; an Experimental study.

The effect of severe soft tissue injury on the severity of hemorrhagic shock is still unknown. Therefore, the present study was aimed to determine hemodynamic and metabolic changes in traumatic/hemorrhagic shock in an animal model. Forty male rats were randomly divided into 4 equal groups including sham, hemorrhagic shock, soft tissue injury, and hemorrhagic shock + soft tissue injury groups. The changes in blood pressure, central venous pressure (CVP) level, acidity (pH), and base excess were dynamically monitored and comparedsented. Mean arterial blood pressure decreased significantly in hemorrhagic shock (df: 12; F=10.9; p<0.001) and severe soft tissue injury + hemorrhagic shock (df: 12; F=11.7; p<0.001) groups 15 minutes and 5 minutes after injury, respectively. A similar trend was observed in CVP in severe soft tissue injury + hemorrhagic shock group (df: 12; F=8.9; p<0.001). After 40 minutes, pH was significantly lower in hemorrhagic shock (df: 12; F=6.8; p=0.009) and severe soft tissue injury + hemorrhagic shock (df: 12; F=7.9; p=0.003) groups. Base excess changes during follow ups have a similar trend. (df: 12; F=11.3; p<0.001). The results of this study have shown that the effect of hemorrhage on the decrease of mean arterial blood pressure, CVP, pH, and base excess is the same in the presence or absence of soft tissue injury.

Saline Versus Plasma-Lyte A in Initial Resuscitation of Trauma Patients

We sought to compare resuscitation with 0.9% NaCl versus Plasma-Lyte A, a calcium-free balanced crystalloid solution, hypothesizing that Plasma-Lyte A would better correct the base deficit 24 hours after injury. Sodium chloride (0.9%) (0.9% NaCl), though often used for resuscitation of trauma patients, may exacerbate the metabolic acidosis that occurs with injury, and this acidosis may have detrimental clinical effects. We conducted a randomized, double-blind, parallel-group trial (NCT01270854) of adult trauma patients requiring blood transfusion, intubation, or operation within 60 minutes of arrival at the University of California Davis Medical Center. Based on a computer-generated, blocked sequence, subjects received either 0.9% NaCl or Plasma-Lyte A for resuscitation during the first 24 hours after injury. The primary outcome was mean change in base excess from 0 to 24 hours. Secondary outcomes included 24-hour arterial pH, serum electrolytes, fluid balance, resource utilization, and in-hospital mortality. Of 46 evaluable subjects (among 65 randomized), 43% had penetrating injuries, injury severity score was 23 ± 16, 20% had admission systolic blood pressure less than 90 mm Hg, and 78% required an operation within 60 minutes of arrival. The baseline pH was 7.27 ± 0.11 and base excess -5.9 ± 5.0 mmol/L. The mean improvement in base excess from 0 to 24 hours was significantly greater with Plasma-Lyte A than with 0.9% NaCl {7.5 ± 4.7 vs 4.4 ± 3.9 mmol/L; difference: 3.1 [95% confidence interval (CI): 0.5-5.6]}. At 24 hours, arterial pH was greater [7.41 ± 0.06 vs 7.37 ± 0.07; difference: 0.05 (95% CI: 0.01-0.09)] and serum chloride was lower [104 ± 4 vs 111 ± 8 mEq/L; difference: -7 (95% CI: -10 to -3)] with Plasma-Lyte A than with 0.9% NaCl. Volumes of study fluid administered, 24-hour urine output, measures of resource utilization, and mortality did not significantly differ between the 2 arms. Compared with 0.9% NaCl, resuscitation of trauma patients with Plasma-Lyte A resulted in improved acid-base status and less hyperchloremia at 24 hours postinjury. Further studies are warranted to evaluate whether resuscitation with Plasma-Lyte A improves clinical outcomes.

Hypernatremic alkalosis or chloride depletion alkalosis?

Dear Editor, We read with interest the article by Lindner et al. [1], where it is suggested that hypernatremia can lead to an increase in standard base excess (SBE). In this study, base excess caused by changes in sodium is 4.1 mmol/L when peak sodium is achieved. At the same time, no change in base excess due to chloride changes is seen from last normal to peak sodium levels. These variations in base excess were calculated taking into account normal values for sodium and chloride. While sodium has a wide normal range of values (135–145 mmol/L), the authors choose 140 mmol/L as a normal value. It is more difficult to determine a normal value for chloride levels, mainly in patients with hypernatremia. The authors choose to correct chloride using the Nanormal ? /Na ratio, taking the assumption that the Cl/ Na ratio remains constant in sodium disorders. However, other studies [2, 3], have demonstrated that the sodium–chloride difference is more accurate than the Cl/Na ratio to identify acid–base disorders. This approach can hide the effect of chloride in SBE changes. The physicochemical approach states that an apparent strong ion difference (SIDa) is a determinant of acid base status and not the variation of an isolated ion. Using this principle, another interpretation of the findings presented by Lindner et al. can be that a failure by chloride to augment in the same proportion of sodium level can lead to metabolic alkalosis in patients with hypernatremia, maintaining what has been proposed by Luke and Galla when they suggested the term chloride depletion alkalosis [4]. To investigate which ion is associated with SBE, we analyzed partial data from a prospective study with patients admitted at emergency department. We obtained signed informed consent from the patients, and the protocol was approved by the local ethics committee. We included 312 patients (61.8 % males) with a mean age of 58.2 ± 12.1 years. Arterial blood samples were collected at emergency department. Overall, 38 (12.2 %) patients had hypernatremia and only 5 hypernatremic patients had had a positive SBE. Mean SBE in hypernatremic patients was not higher than in those with normal sodium levels (-7.58 ± 4.68 vs. -6.82 ± 4.06 mmol/L, p = 0.556). On the other hand, when patients were divided according to chloride levels, patients with absolute hypochloremia and no hypernatremia (serum chloride \95 mmol/L, n = 39) had a higher SBE than others (-4.5 ± 7.29 vs. -7.38 ± 4.60 mmol/L, p = 0.02). When all patients were analyzed regarding the association of physicochemical determinants of acid base status with SBE (Table 1), there was no association between sodium levels and SBE, while chloride level is associated with SBE even after controlling for other determinants of acid base status. Hypernatremia at emergency department is generally due water deficit, while hypertonic solutions can be the main responsible in ICU patients. Although not explored by Lindner et al., expansion solutions are generally rich in chloride with a SID near zero, favoring a state of acidosis

Last Word on Point:Counterpoint: Lactic acid is/is not the only physicochemical contributor to the acidosis of exercise

to the editor: We grounded our positions on arguments and quantitative considerations ([2][1]) while the counterpoint supporters often present only statements. Beginning with Van Slyke, we studied a bulk of acid base literature, therefore it is somewhat amusing that we, according to Lindinger and

Rebuttal from Drs. Böning and Maassen

POINT-COUNTERPOINTRebuttal from Drs. Böning and MaassenPublished Online:01 Jul 2008https://doi.org/10.1152/japplphysiol.00162.2008bMoreSectionsPDF (38 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Besides our criticism concerning SID we disagree with the following Counterpoint statements (6). First, “…arterial blood does not provide an ‘average’ representation of acid-base balance within the body.” Concentration differences in venous outflow from organs are averaged in mixed venous blood being representative for 90% of the blood. After lung passage blood composition is unchanged except for gases since lung cell and interstitial volumes are too small to exert measurable effects on electrolytes. Therefore arterial blood represents nonrespiratory acid-base changes in blood, but of course not in the body.Concerning BE we are astonished about some arguments since we have clearly discerned (1) in vitro (actual, ABE) and in vivo (standard, SBE) conditions. The BE concept is determination of added fixed acid by back-titration to pH 7.4 at constant Pco2 and O2 saturation using buffer values of blood with actual [Hb] (ABE) or diluted with interstitial fluid (assumed [Hb] 5 g/dl, SBE). This includes normal [2,3-diphosphoglycerate], which is constant during short exercise (4). Under pure in vitro conditions titration with lactic acid yields equal changes (Δ) of [La]blood and ABE (1, 3). When applying ABE to arterialized blood during exercise deviations of Pco2 from 40 mmHg are small, calculation errors for this effect being negligible. Not considered are changes in plasma [protein] and [phosphate] but this error is small. [Protein] increases by fluid shift to tissues even cause alkalosis (5), not acidosis (6) at constant Pco2.The SBE concept has been confirmed by in vivo CO2 titrations (reviewed in Ref. 2). When calculating exercise-induced ΔSBE, changes of [Hb] are not considered, but deviations are not important for calculation. Therefore our results [near equality between −ΔABE and Δ[La] + Δ [Cl−] in blood as well as between −ΔSBE and the average of Δ[La] in blood and interstitial fluid after exhaustion (1)] are not coincidental but evidence of lactic acid as cause of nonrespiratory acidosis. During exercise the effect of extracellular volume shrinking on [HCO3−] is additionally mirrored in changes of ABE and SBE.The statement on nonexistence of the Donnan equilibrium holds only for cations. The Donnan equilibrium is an electrochemical equilibrium. In contrast to active cation pumps passive transporters like Cl− HCO3− exchangers or La− H+ cotransporters as well as enzymes (carboanhydrases) do not change the equilibrium but only shorten the time for regaining it after disturbances. For La− this lasts minutes and is often completed only during recovery (1).REFERENCES1 Böning D, Klarholz C, Himmelsbach B, Hütler M, Maassen N. Causes of differences in exercise-induced changes of base excess and blood lactate. Eur J Appl Physiol 99: 163–171, 2007.Crossref | PubMed | ISI | Google Scholar2 Böning D, Klarholz C, Himmelsbach B, Hütler M, Maassen N. Extracellular bicarbonate and non-bicarbonate buffering against lactic acid during and after exercise. Eur J Appl Physiol 100: 457–467, 2007.Crossref | ISI | Google Scholar3 Böning D, Maassen N. Blood osmolality in vitro: dependence on Pco2, lactic acid concentration, and O2 saturation. J Appl Physiol Respir 54: 118–122, 1983.Link | ISI | Google Scholar4 Braumann KM, Böning D, Trost F. Bohr effect and slope of the oxygen dissociation curve after physical training. J Appl Physiol Respir Environ Exerc Physiol 52: 1524–1529, 1982.Link | ISI | Google Scholar5 Lang W, Zander R. Prediction of dilutional acidosis based on the revised classical dilution concept for bicarbonate. J Appl Physiol 98: 62–71, 2005.Link | ISI | Google Scholar6 Lindinger MI, Heigenhauser GJF. Counterpoint: Lactic acid is not the only physicochemical contributor to the acidosis of exercise. J Appl Physiol; doi:10.1152/japplphysiol.00162.2008a.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 105Issue 1July 2008Pages 361-361 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00162.2008bHistory Published online 1 July 2008 Published in print 1 July 2008 Metrics

Pharmacokinetics of potassium bromide in adult horses

To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. Twelve adult Standardbred and Thoroughbred mares. Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of concentration versus time curves from which pharmacokinetic parameters could be calculated. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. Maximum mean serum bromide concentration following a single dose of KBr (120 mg/kg) was 284 +/- 15 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 days) gave a maximum serum bromide concentration of 1098 +/- 105 microg/mL. The administration of lower, maintenance doses of KBr (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 700 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. A loading dose of 120 mg/kg daily over 5 days and maintenance doses of approximately 90-100 mg/kg of KBr administered once daily are predicted to result in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.

Causes of differences in exercise-induced changes of base excess and blood lactate

It has been concluded from comparisons of base excess (BE) and lactic acid (La) concentration changes in blood during exercise-induced acidosis that more H+ than La- leave the muscle and enter interstitial fluid and blood. To examine this, we performed incremental cycle tests in 13 untrained males and measured acid-base status and [La] in arterialized blood, plasma, and red cells until 21 min after exhaustion. The decrease of actual BE (-deltaABE) was 2.2 +/- 0.5 (SEM) mmol l(-1) larger than the increase of [La]blood at exhaustion, and the difference rose to 4.8 +/- 0.5 mmol l(-1) during the first minutes of recovery. The decrease of standard BE (SBE), a measure of mean BE of interstitial fluid (if) and blood, however, was smaller than the increase of [La] in the corresponding volume (delta[La](if+blood)) during exercise and only slightly larger during recovery. The discrepancy between -deltaABE and delta[La]blood mainly results from the Donnan effect hindering the rise of [La]erythrocyte to equal values like [La]plasma. The changing Donnan effect during acidosis causes that Cl- from the interstitial fluid enter plasma and erythrocytes in exchange for HCO3(-). A corresponding amount of La- remains outside the blood. SBE is not influenced by ion shifts among these compartments and therefore is a rather exact measure of acid movements across tissue cell membranes, but changes have been compared previously to delta[La]blood instead to delta[La](if+blood). When performing correct comparisons and considering Cl-/HCO3(-) exchange between erythrocytes and extracellular fluid, neither the use of deltaABE nor of deltaSBE provides evidence for differences in H+ and La- transport across the tissue cell membranes.

Early venovenous haemodiafiltration for sepsis-related multiple organ failure

In a prospective observational study that included 60 consecutive patients over a 10-year period, Page and coworkers [1] studied the effects of early continuous venovenous haemodiafiltration (CVVHDF) during sepsis-induced multiple organ failure. In two-thirds of the patients rapid metabolic improvement during CVVHDF was associated with circulatory improvement and a low mortality rate, whereas lack of metabolic improvement after 12 hours of CVVHDF (mainly based on changes in base excess) was associated with a 100% mortality rate. The authors concluded that early CVVHDF may improve the prognosis of sepsis-related multiple organ failure, and that failure to correct metabolic acidosis rapidly during the procedure is a strong predictor of mortality. In that study, metabolic acidosis was assessed using base excess values, and the authors highlighted the influence of individual changes 6-12 hours after initiation of CVVHDF on predicted outcome. However, despite the findings reported, the usefulness of base excess is questionable. First, because of the high incidence of circulatory failure occurring after several days of hospitalization, base excess may be influenced by large volume crystalloid infusion, resulting in altered protein status. Second, the link between base excess and lactate concentration was weak (r 2 = 0.36 for the patients studied). We believe that lactate values may be more important in predicting outcome than base excess. Indeed, it is widely accepted that early lactate clearance is associated with improved outcomes in septic shock [2] and that lactate levels are not affected by CVVHDF [3]. In the study by Page and coworkers [1] one cannot exclude the possibility that the lack of improvement in base excess in the nonresponder group was linked to persistent lactate production, and so metabolic improvement during the procedure is not necessarily superior to the trend in blood lactate as a predictive tool.

A method for calculation of arterial acid–base and blood gas status from measurements in the peripheral venous blood

In non-emergency medical departments such as internal medicine sampling of arterial blood and analysis for acid–base status is not routinely performed. Peripheral venous blood is routinely taken but interpretation of its acid–base status is difficult. This paper presents a method for calculation of arterial acid–base and blood gas status from measurements in peripheral venous blood combined with a pulse oximeter measurement of arterial saturation. The use of the method has been illustrated using the data of three patients with different acid–base, haemodynamic, and metabolic conditions. The sensitivity of the method has been tested for measurement errors including venous blood acid–base and blood gas status and pulse oximetry; errors due to physiological assumptions including the values of RQ and strong acid production at the tissues; and errors due to air bubbles in the blood. Errors due to these effects are relatively insignificant except for errors in calculated arterial PO 2, particularly when SpO 2 is greater than 97%; and errors when the change in base excess across the sampling site due to strong acid production is greater that 1.3 mmol/l.

Pharmacokinetics of potassium bromide in adult horses

To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. Twelve adult Standardbred and Thoroughbred mares. Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. Maximum mean serum concentration following a single dose of KBr (120 mg/kg) was 423 +/- 22 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 d) gave a maximum serum concentration 1639 +/- 156 microg/mL. The administration of lower, maintenance doses (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 1000 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. and clinical relevance Loading doses of 120 mg/kg daily over 5 d and maintenance doses of approximately 90 mg/kg of KBr administered once daily resulted in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.

Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution

Extreme hemodilution was performed in the hamster chamber window model using 6% Dextran 70, lowering systemic hematocrit by 60%. Animals were subsequently divided into three groups and hemodiluted to a hematocrit of 11% using 6% Dextran 70, 6% Dextran 500, and a 4% Dextran 70 + 0.7% alginate solution (n = 6 each group). Final plasma viscosities were 1.4 +/- 0.2, 2.2 +/- 0.1, and 2.7 +/- 0.2 cp, respectively, (P < 0.05, high viscosity vs. low viscosity). Blood viscosities were 2.1 +/- 0.2, 2.9 +/- 0.4, and 3.9 +/- 0.3 cp, respectively. The lowest blood and plasma viscosity group had a significantly lower functional capillary density, 37 +/- 16%, whereas the two high-viscosity solutions were 71 +/- 15% and 76 +/- 12% (P < 0.05, high viscosity vs. low viscosity), respectively. Arteriolar and venular flow in the Dextran 500 and alginate groups was higher than baseline (i.e., normal nontreated animals), whereas the low-viscosity group showed a reduction in flow. These microvascular changes were paralleled by changes in base excess, which was negative for the Dextran 70 group and positive for the other groups. However, tissue Po(2) was uniformly low for all groups (average of 1.4 mmHg). Calculation of tissue oxygen consumption in the window chamber based on the microvascular data, flow, and intravascular Po(2) showed that only the alginate + Dextran 70 solution-exchanged animals returned to baseline oxygen consumption, whereas the other groups were lower than baseline (P < 0.05). These results show that hemodilution performed with high-viscosity plasma expanders yields systemic arterial pressures and functional capillary densities that are significantly higher (P < 0.05) than those obtained with 6% Dextran 70, a fluid whose viscosity is similar to that of plasma. A condition for obtaining these results is that the oncotic pressure of the plasma expander be titrated to near normal, so that autotransfusion of fluid from the tissue into the vascular compartment does not reduce the effects of increasing plasma viscosity and increased shear stress on the microvascular wall.

Effect of isotonic and hypotonic lactated ringer's solutions with dextrose intravenously administered to dehydrated heifers.

To determine the effects of rapid infusion of essential fluids in a volume of hypotonic lactated Ringer's solution, the central venous pressure (CVP) and acid-base equilibrium were investigated in to mildly dehydrated heifers. Mild dehydration was induced in 9 Holstein heifers by withholding food and water until 7.0+/-5.7% of plasma volume had been lost. The heifers were randomly assigned to the ILG (lactated Ringer's + 5% dextrose), HLG (1/2 lactated Ringer's + 2.2% dextrose) or HRG (1/2 Ringer's + 2.5% dextrose) groups with 3 heifers in each group. Heifers received 30 ml/kg of one of the fluids, at a flow rate of 20 ml/kg/hr. The rapid intravenous (IV) infusions of HLG and HRG used in this study were found to be safe and effective in increasing plasma volume without increasing CVP, even though the infusion was given to the jugular vein at a dosage of 30 ml/kg. However, ILG infusion induced progressive increases in CVP, reaching 9.0+/-2.0 mmHg. No clinical signs, such as moist rales on auscultation, moist cough, jugular vein congestion, ophthalmoptosis, salivation or arrhythmia, were observed throughout the fluid infusion. The relative changes in base excess (rBE) for the ILG and HRG groups were significantly decreased until the end of fluid infusion. As for the HLG group, rBE slightly decreased until the end of the fluid infusion. Then the values significantly increased and exceeded the pre-infusion value at the end of the experiment. While IV infusion of HLG inhibited acidification caused by dilution, HRG infusion induced diluted acidification. It is suggested that HLG infusion should be examined as a treatment for cattle with dehydration and moderate metabolic acidosis, since rapid infusion of HLG may be more beneficial for rehydrating cattle with metabolic acidosis than current treatment.

Accuracy of base excess--an in vitro evaluation of the Van Slyke equation.

To evaluate the precision, bias and CO2 invariance of base excess as determined by the Van Slyke equation over a wide P(CO2) range at normal and low hemoglobin concentrations. Prospective in vitro study. University research laboratory. Normal human blood, both undiluted and diluted with plasma. Two experiments were conducted. In the first, blood unmodified or after adding HCl or sodium bicarbonate was rendered hypercarbic (P(CO2) >70 torr) by gas equilibration. Rapid Pco2 reduction in > or =10 steps to a final P(CO2) < or =20 torr was then performed. In the second experiment, blood unmodified or diluted to a hemoglobin concentration of approximately 4 G% was mixed anaerobically (9:1, vol:vol) with varying concentrations of lactic acid in saline (0-250 mmol/L). In the first experiment, blood gas analysis at each step during the progressive P(CO2) reduction revealed that base excess remained nearly constant (SD all specimens < or =0.6 mmol/L) whereas P(CO2) changed by >80 torr. In the second experiment, simultaneous blood gas and plasma lactate analyses showed that changes in base excess correlated closely with changes in both plasma and whole blood lactate concentrations (r2 > or = 0.91) despite concurrent P(CO2) elevations as great as 200 torr. Quantification by base excess of change in whole blood lactate concentration was precise with slight negative bias (mean negative bias, 1.1+/-1.9 mmol/L) in both diluted and undiluted blood. There was significant underestimation of change in plasma lactate concentration in undiluted blood, presumably because base excess is a whole blood variable. Base excess calculated using the Van Slyke equation accurately quantifies metabolic (nonrespiratory) acid-base status in blood in vitro. This accuracy is little affected by large simultaneous alterations in P(CO2), or by very low hemoglobin concentrations similar to that used to calculate standard base excess.

Induction of acute metabolic acid/base changes in humans.

The aim of this study was to induce acute metabolic acid/base changes of > or = 2 mequiv.l-1 change in base excess (BE) to aid future investigations of respiratory parameters under these conditions. Ammonium chloride (NH4Cl) was administered to induce acidification and furosemide was used to induce alkalization. Nine healthy volunteers (six men and three women aged 35 +/- 18 years) ingested a calculated amount of NH4Cl at t = 0 and a repeat dose after 60 min. Eight healthy volunteers (three men and five women aged 37 +/- 16 years) consumed 40 mg of furosemide. Arterialized capillary blood gases were measured at t = 0, 30, 60, 90, 120 and 180 min. In the case of acute metabolic acidosis, the target acidification of 2 mequiv.l-1 was attained after 30 min and the greatest change was achieved at 90 min: -4.9 (2.2) mequiv.l-1. In the case of acute metabolic alkalosis, the target alkalization of 2 mequiv.l-1 was reached between 120 and 180 min and the greatest change was seen at 180 min: +2.2 (1.4) mequiv.l-1. Significant (P < 0.05) changes in acidification compared with baseline BE values were found between 60 and 180 min; significant (P < 0.05) changes in alkalization were found between 120 and 150 min. PaCO2 did not change significantly in either condition. We conclude that NH4Cl and furosemide induce a steady state of pure metabolic acid/base conditions in humans, which is buffered in an isocapnic manner.

Anaerobic threshold determination and its importance in chronic heart failure patients

The goal of this study was to compare various methods of anaerobic threshold (AT) determination and to estimate its importance for both the prescription of appropriate physical activity and long‐term follow‐up evaluation in patients with chronic heart failure (CHF). Twenty‐eight persons (New York Heart Association Classification II, III) passed a symptom‐limited spiroergometrical test; some of them were serially measured. The incremental work rate was graded by 0.25 W‐kg‐1 every 4 minutes. AT was determined from ventilatory parameters (VT), on the one hand, and from base excess changes (—BET), on the other. VT was determined in 79% and —BET in 50% of patients. The correlation between other functional parameters and both VT and ‐BET parameters was close (r = 0.94 for heart rate, for example). The possibility of making an AT determination decreased in Weber's class C patients. AT determination was also possible in persons showing a change in acid‐base balance at rest. Basic functional parameters (heart rate...