Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

Factors Influencing Blood Alkalosis and Other Physiological Responses, Gastrointestinal Symptoms, and Exercise Performance Following Sodium Citrate Supplementation: A Review.

This review aimed to identify factors associated with (a) physiological responses, (b) gastrointestinal (GI) symptoms, and (c) exercise performance following sodium citrate supplementation. A literature search identified 33 articles. Observations of physiological responses and GI symptoms were categorized by dose (< 500, 500, and > 500 mg/kg body mass [BM]) and by timing of postingestion measurements (in minutes). Exercise performance following sodium citrate supplementation was compared with placebo using statistical significance, percentage change, and effect size. Performance observations were categorized by exercise duration (very short < 60 s, short ≥ 60 and ≤ 420 s, and longer > 420 s) and intensity (very high > 100% VO2max and high 90-100% VO2max). Ingestion of 500 mg/kg BM sodium citrate induced blood alkalosis more frequently than < 500 mg/kg BM, and with similar frequency to >500 mg/kg BM. The GI symptoms were minimized when a 500 mg/kg BM dose was ingested in capsules rather than in solution. Significant improvements in performance following sodium citrate supplementation were reported in all observations of short-duration and very high-intensity exercise with a 500 mg/kg BM dose. However, the efficacy of supplementation for short-duration, high-intensity exercise is less clear, given that only 25% of observations reported significant improvements in performance following sodium citrate supplementation. Based on the current literature, the authors recommend ingestion of 500 mg/kg BM sodium citrate in capsules to induce alkalosis and minimize GI symptoms. Supplementation was of most benefit to performance of short-duration exercise of very high intensity; further investigation is required to determine the importance of ingestion duration and timing.

Metabolic Alkalosis in the Pediatric Patient: Treatment Options in the Pediatric ICU or Pediatric Cardiothoracic ICU Setting.

Metabolic alkalosis is characterized by the primary elevation of the serum bicarbonate concentration with a normal or elevated partial pressure of carbon dioxide. Although there may be several potential etiologies in the critically ill patient in the pediatric or cardiothoracic intensive care unit, metabolic alkalosis most commonly results from diuretic therapy with chloride loss. In most cases, the etiology can be determined by a review of the patient's history and medication record. Although generally innocuous with limited impact on physiologic function, metabolic alkalosis may impair central control of ventilation, especially when weaning from mechanical ventilation. The following manuscript presents the normal homeostatic mechanisms that control pH, reviews the etiology of metabolic alkalosis, and outlines the differential diagnosis. Options and alternatives for treatment including pharmacologic interventions are presented with a focus on these conditions as they pertain to the patient in the pediatric or cardiac intensive care unit.

Metabolic Alkalosis: A Brief Pathophysiologic Review.

Metabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms. Multiple mechanisms are also responsible for the persistence, or maintenance, of metabolic alkalosis. Understanding these generation and maintenance mechanisms helps direct appropriate intervention and correction of this disorder. The framework utilized in this review is based on the ECF volume-centered approach popularized by Donald Seldin and Floyd Rector in the 1970s.  Although many subsequent scientific discoveries have advanced our understanding of the pathophysiology of metabolic alkalosis, that framework continues to be a valuable and relatively straightforward diagnostic and therapeutic model.

Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China.

Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.

The arterial blood gas algorithm: Proposal of a systematic approach to analysis of acid-base disorders. / El algoritmo de la gasometría arterial: propuesta de un enfoque sistemático para el análisis de los trastornos del equilibrio ácido-base.

Abnormalities in the acid-base balance are common clinical problems and can have deleterious effects on cellular function and be a clue to various disorders. Therefore, it is important for the clinician to make a precise diagnosis of the acid-base disorder(s) present for a proper treatment. Three approaches have been proposed to evaluate acid-base disorders: a bicarbonate-centric approach; the Stewart approach, and the base excess approach. Although the latter two have many adherents, we will only discuss the bicarbonate-centric approach. This approach is simpler to utilize at the bedside, has a physiological evaluation of the acid-base disorder, presents an easily understandable approach to assess severity, and provides a more solid foundation for the development of effective therapies. Therefore, the following discussion will be limited to an examination of this approach. In this case-centric review, important new concepts will be introduced first; their benefits and limitations discussed; and then their utilization to analyze actual cases will be shown. A systematic approach algorithm that incorporates these new concepts has been generated and will be highlighted.

Sodium citrate ingestion protocol impacts induced alkalosis, gastrointestinal symptoms, and palatability.

To compare the effect of 500 mg·kg-1 body mass (BM) sodium citrate ingested in solution or capsules on induced alkalosis, gastrointestinal symptoms and palatability. Twenty-four healthy and active participants completed two testing sessions, ingesting 500 mg·kg-1 BM sodium citrate within solution or capsules. Capillary blood samples were collected pre-ingestion, and every 30-min for 240-min post-ingestion; samples were analyzed for blood pH and [HCO3- ]. A validated questionnaire was used to quantify gastrointestinal symptoms at the same 30-min intervals. Palatability was quantified immediately after ingestion using a validated scale. There was a greater peak and change from baseline for capsules versus solution for blood pH (P < 0.001) and [HCO3- ] (P = 0.013). Blood pH and [HCO3- ] time to peak was 199 and 204 min, respectively, after capsule ingestion, both significantly later than after solution (P = 0.034, P = 0.001). Gastrointestinal symptoms were significantly elevated above baseline for both ingestion modes at each time point between 30 and 120 min after ingestion (P = 0.003), with no differences between modes at any time point (P = 0.644). Capsules were significantly more palatable than solution (P < 0.001). We recommend 500 mg·kg-1 BM sodium citrate ingestion in capsules, at least 200 min before exercise, to achieve greater alkalosis, minimize gastrointestinal symptoms, and maximize.

The utility of next generation sequencing in the correct diagnosis of congenital hypochloremic hypokalemic metabolic alkalosis.

Persistent hypokalemic hypochloremic metabolic alkalosis represents a heterogeneous group of genetic disorders of which the most common is Bartter syndrome (BS). BS is an inherited renal tubulopathy caused by defective salt reabsorption in the thick ascending loop of Henle, which results in persistent hypokalemic hypochloremic metabolic alkalosis. Here we report a 10-year-old girl of a consanguineous family. She presented prenatally with severe polyhydramnios and distended bowel loops. Thereafter, she displayed failure to thrive and had recurrent admissions due to dehydration episodes associated with diarrhea, and characterized by hypokalemia, hypochloremia and metabolic alkalosis. BS was considered her working diagnosis for several years despite negative genetic analysis of the known genes associated with BS. Whole exome sequencing identified a novel homozygous c.1652delT deleterious frameshift mutation in the SLC26A3 gene, which confirmed the diagnosis of congenital chloride diarrhea (CCD), a rare autosomal recessive disease that mimics biochemically BS. A review of twelve additional reported cases of CCD that were initially misdiagnosed as BS, emphasizes CCD in the differential diagnosis of BS, and highlights the clinical discrepancies between these two entities. Taken together, our report further emphasizes the typical clinical features of CCD, and the importance of next generation sequencing in the diagnosis of syndromes with genetic heterogeneity. We suggest including SLC26A3 in the extended BS targeted gene panels.

Effect of Bicarbonate-Buffered Dialysate on Ventricular Arrhythmias in Hemodialysis Patients.

BACKGROUND: The etiology of sudden cardiac death in patients with end-stage renal disease (ESRD) on hemodialysis (HD) is largely unknown, though there is evidence to suggest that metabolic alkalosis induced by HD with a high-bicarbonate dialysate/prescription may play a role. METHODS: We investigated the effects of metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate on frequency of ventricular arrhythmia in 47 patients with ESRD on chronic HD using 48-h Holter monitoring in 3 phases: intra-HD, post-HD day 1, and post-HD day 2. Serum levels of bicarbonate, calcium, and potassium along with hemodynamics were measured pre-HD, post-HD, 20-h post-HD, and 44-h post-HD. Correlations were performed to verify the association between bicarbonate prescription and change in serum bicarbonate levels post-HD and to determine if the HD-induced change in serum bicarbonate level (metabolic alkalosis) had any direct association with ambient ventricular arrhythmia (premature ventricular contractions per hour) or indirect associations with ambient ventricular arrhythmia by affecting electrolytes or hemodynamics that are known to increase the risk of ventricular arrhythmia. RESULTS: Mean pre-HD serum bicarbonate level was 21.3 mEq/L. Dialysate bicarbonate prescription (mean of 36.4 mEq/L) correlated with changes in serum bicarbonate levels immediately post-HD 26.7 mEq/L (r = 0.46, p < 0.01), 20-h post-HD 25.2 mEq/L (r = 0.38), and 44-h post-HD 23.2 mEq/L (r = 0.35, p = 0.01). No statistically significant correlations were found between the post-HD change in serum bicarbonate levels (metabolic alkalosis) with ambient ventricular arrhythmia, changes in serum calcium, potassium, or hemodynamics in any phase. CONCLUSIONS: High-bicarbonate dialysate prescription is associated with metabolic alkalosis following the HD procedure. A mild metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate solution had no direct association with ambient ventricular arrhythmia on Holter monitoring and was not associated with changes in hemodynamics or changes in serum total calcium or potassium levels. This study helps to provide guidance for the safe use of high bicarbonate dialysate/prescription in patients with ESRD on HD.

Insulin infusion responses in diabetic ketoacidosis alone and with a mixed hypochloremic alkalosis.

AIMS: Although diabetic ketoacidosis (DKA) commonly presents as a pure diabetic ketoacidosis (PDKA), up to 30% of cases may be associated with a mixed hypochloremic metabolic alkalosis (HMA). It is unknown whether there is a difference in treatment outcomes between these two entities. We evaluated an insulin infusion protocol (IIP), previously validated for hyperglycemia management in ICU's, for the management of PDKA and HMA. MATERIALS AND METHODS: A retrospective case series/cohort study of 41 DKA admissions was further characterized as having PDKA or HMA. HMA was defined in those having an elevated delta-delta gradient (ΔAG-ΔHCO3) ≥ 5 mmol/L and base excess chloride (BECl) > 2.7 mmol/L. The main outcome measures were times to recovery of glucose levels to ≤250 mg/dL and of anion gap to ≤12 mmol/L. RESULTS: The initial serum glucose was 553 ±â€¯265 mg/dL, serum bicarbonate of 8.8 ±â€¯5.1 mmol/L, and venous pH 7.13 ±â€¯0.2). Recovery of glucose occurred in 5 h: 25 min (±3 h:39min), and for anion gap in 11 h:25 min (±6 h:56min). HMA compared with PDKA had a delayed recovery of serum glucose (7 h: 23min ±â€¯3 h: 35min vs. 4 h: 31min ±â€¯3:h:21min, p = 0.017), which was due to the higher initial level of glucose (p = 0.02) rather than level of BECl (p = 0.17). There was no difference in time to anion gap closure between the PDKA and HMA. CONCLUSIONS: Correction of hyperglycemia and acidosis in PDKA as well as in HMA was managed through the IIP. The simultaneous fluid and electrolyte management corrected the hypochloremic alkalosis.

High doses of sodium bicarbonate increase lactate levels and delay exhaustion in a cycling performance test.

OBJECTIVES: It is well established that ingestion of sodium bicarbonate (NaHCO3) causes metabolic alkalosis. However, there is no consensus in terms of optimal NaHCO3 doses leading to enhanced performance. This study aimed to determine the effects of different NaHCO3 doses on performance and lactate clearance in non-professional cyclists. METHODS: Twenty-one cyclists performed the following three double-blind trials: 1) ingestion of 0.3 g · kg-1 body weight (BW) of placebo; 2) ingestion of 0.1 g · kg-1 BW NaHCO3 plus 0.2 g · kg-1 BW placebo (0.1 BC); and 3) ingestion of 0.3 g · kg-1 BW NaHCO3 (0.3 BC). Performance was evaluated after warm-up on the bike followed by a performance test until exhaustion. Lactate levels were monitored in blood samples before and immediately after performance tests. RESULTS: Lactate levels in the blood were significantly higher after exercise in 0.3 BC and 0.1 BC (15.12 ± 0.92 versus 10.3 ± 1.22 and 13.24 ± 0.87 versus 10.3 ± 1.22 mmol/L; P < 0.05) compared with control. Significant improvements in performance were only identified in 0.3 BC group (76.42 ± 2.14; P = 0.01). CONCLUSIONS: The present study found that 0.3 g · kg-1 BW NaHCO3 is effective in improving performance and improving blood lactate levels in cyclists compared with control and 0.1 g · kg-1 BW NaHCO3.

Effect of induced alkalosis on performance during a field-simulated BMX cycling competition.

OBJECTIVES: The aim of the present study was to test the effect of sodium bicarbonate (NaHCO3-) ingestion on performance during a simulated competition on a Bicycle Motocross (BMX) track. DESIGN: Double-blind cross-over study. METHODS: Twelve elite male BMX cyclists (age: 19.2±3.4 years; height: 174.2±5.3cm; body mass: 72.4±8.4kg) ingested either NaHCO3- (0.3g.kg-1 body weight) or placebo 90min prior to exercise. The cyclists completed three races in a BMX Olympic track interspersed with 15min of recovery. Blood samples were collected to assess the blood acid-base status. Performance, cardiorespiratory, heart rate variability (HRV) as well as subjective variables were assessed. RESULTS: The main effect of condition (NaHCO3- vs. placebo) was observed in pH, bicarbonate concentration and base excess (p<0.05), with a significant blood alkalosis. No changes were found in time, peak velocity and time to peak velocity for condition (p>0.05). The HRV analysis showed a significant effect of NaHCO3- ingestion, expressed by the rMSSD30 (root mean square of the successive differences) (p<0.001). There was no effect of condition on oxygen uptake, carbon dioxide production, or pulmonary ventilation (p>0.05). Finally, there was no effect of condition for any subjective scale (p>0.05). CONCLUSIONS: We present here the first field condition study to investigate the effect of bicarbonate ingestion over performance in BMX discipline. The results showed that NaHCO3--induced alkalosis did not improve performance in a simulated BMX competition in elite BMX cyclists, although future studies should consider the effects of NaHCO3- on autonomic function as a component of recovery.

Diabetic ketoalkalosis: misnomer or undiagnosed variant of diabetic ketoacidosis.

Usually, hyperglycaemia crisis presents with acidotic pH, but ketoalkalosis is a rare and unheard entity presenting in diabetic ketoacidosis. We describe three unique cases where the patients present with hyperglycaemia >250 mg/dL, normal or alkalotic pH, and bicarbonate >20 meq/L, which does not meet criteria for diabetic ketoacidosis. However, once these patients were supplemented with intravenous fluids, diagnosis of diabetic ketoacidosis was evident in laboratory analysis. These case series provide a learning opportunity in diagnosing and management of this rare phenomenon.

Potassium conservation is impaired in mice with reduced renal expression of Kir4.1.

To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression. Lethality by ~3 wk, however, limits the usefulness of this model, so we developed a kidney-specific Kir4.1 "knockdown" mouse (ksKD) using a cadherin 16 promoter and Cre-loxP methodology. These mice appeared normal and survived to adulthood. Kir4.1 protein expression was decreased ~50% vs. wild-type (WT) mice by immunoblotting, and immunofluorescence showed moderately reduced Kir4.1 staining in distal convoluted tubule that was minimal or absent in connecting tubule and cortical collecting duct. Under control conditions, the ksKD mice showed metabolic alkalosis and relative hypercalcemia but were normokalemic and mildly hypermagnesemic despite decreased NCC expression. In addition, the mice had a severe urinary concentrating defect associated with hypernatremia, enlarged kidneys with tubulocystic dilations, and reduced aquaporin-3 expression. On a K/Mg-free diet for 1 wk, however, ksKD mice showed marked hypokalemia (serum K: 1.5 ± 0.1 vs. 3.0 ± 0.1 mEq/l for WT), which was associated with renal K wasting (transtubular K gradient: 11.4 ± 0.8 vs. 1.6 ± 0.4 in WT). Phosphorylated-NCC expression increased in WT but not ksKD mice on the K/Mg-free diet, suggesting that loss of NCC adaptation underlies the hypokalemia. In conclusion, even modest reduction in Kir4.1 expression results in impaired K conservation, which appears to be mediated by reduced expression of activated NCC.