Acid-base Disorders Research Articles

Phenome-wide association of 1809 phenotypes and COVID-19 disease progression in the Veterans Health Administration Million Veteran Program.

BackgroundThe risk factors associated with the stages of Coronavirus Disease-2019 (COVID-19) disease progression are not well known. We aim to identify risk factors specific to each state of COVID-19 progression from SARS-CoV-2 infection through death.Methods and resultsWe included 648,202 participants from the Veteran Affairs Million Veteran Program (2011-). We identified characteristics and 1,809 ICD code-based phenotypes from the electronic health record. We used logistic regression to examine the association of age, sex, body mass index (BMI), race, and prevalent phenotypes to the stages of COVID-19 disease progression: infection, hospitalization, intensive care unit (ICU) admission, and 30-day mortality (separate models for each). Models were adjusted for age, sex, race, ethnicity, number of visit months and ICD codes, state infection rate and controlled for multiple testing using false discovery rate (≤0.1). As of August 10, 2020, 5,929 individuals were SARS-CoV-2 positive and among those, 1,463 (25%) were hospitalized, 579 (10%) were in ICU, and 398 (7%) died. We observed a lower risk in women vs. men for ICU and mortality (Odds Ratio (95% CI): 0.48 (0.30–0.76) and 0.59 (0.31–1.15), respectively) and a higher risk in Black vs. Other race patients for hospitalization and ICU (OR (95%CI): 1.53 (1.32–1.77) and 1.63 (1.32–2.02), respectively). We observed an increased risk of all COVID-19 disease states with older age and BMI ≥35 vs. 20–24 kg/m2. Renal failure, respiratory failure, morbid obesity, acid-base balance disorder, white blood cell diseases, hydronephrosis and bacterial infections were associated with an increased risk of ICU admissions; sepsis, chronic skin ulcers, acid-base balance disorder and acidosis were associated with mortality.ConclusionsOlder age, higher BMI, males and patients with a history of respiratory, kidney, bacterial or metabolic comorbidities experienced greater COVID-19 severity. Future studies to investigate the underlying mechanisms associated with these phenotype clusters and COVID-19 are warranted.

Immune Checkpoint Inhibitor-Induced Hypophysitis in Renal Cell Carcinoma: Two Contrasting Case Presentations

Background: Increasing use of immune checkpoint inhibitor (ICI) therapy for malignancy has led to rising incidence of ICI-mediated endocrinopathies. We describe two varying cases of patients with renal cell carcinoma (RCC) who presented with ICI-mediated hypophysitis. Cases: Patient A: A 72 year old female with RCC (T1bN0M0) diagnosed after an incidental renal mass was found on CT scan following a motor vehicle accident. After nephrectomy, she received 5 cycles of nivolumab (6/2019 to 10/2019). One month later, she presented in severe DKA and was diagnosed with ICI-mediated diabetes (low c-peptide, negative autoantibodies). ICI therapy was stopped. In 4/2020, she experienced a drastic reduction in her insulin requirement (~30 units/day of basal/bolus insulin to ~6 units/day of basal insulin only). She had a primary care visit for fatigue, nausea, and anorexia. Biochemical evaluation showed hyponatremia, normokalemia, normoglycemia, and no acid-base disorder. One week later, she presented to the emergency department (ED) with worsening symptoms. She was hypotensive (94/56 mmHg), hyponatremic (129 mmol/L), normokalemic, and azotemic. Cosyntropin stimulation test (CST) showed an inappropriate response [ACTH <5 pg/ml; cortisol response of 0.4 to 8.1 µg/dl]. Brain MRI showed a partially empty sella. She was diagnosed with secondary adrenal insufficiency (AI) due to hypophysitis and started on steroid replacement. A repeat CST after 3 months did not show HPA axis recovery. Her presentation is unique because she developed secondary AI six months after nivolumab therapy. Patient B: A 43 year old female with RCC (T4N1M1) who received 4-cycles of ipilimumab and nivolumab (11/2019 to 1/2020). One month later, she presented to the ED with hypotension, anorexia, and fatigue. Biochemical evaluation showed severe DKA. She was diagnosed with ICI-mediated diabetes (low c-peptide, negative autoantibodies) and started on basal/bolus insulin. Her ICI-therapy was stopped. One month later, she was readmitted for hypotension and severe headaches and found to have hyponatremia (131 mmol/L), normokalemia, hyperprolactinemia (29 ng/ml), cortisol 4.5 µg/dl (previous random cortisol a month earlier was 33 µg/dl). Pituitary gland was normal on MRI. She was presumed to have secondary AI due to hypophysitis and started on steroid replacement. A CST performed after 3 months showed ACTH <5 pg/ml and cortisol response of 3.5 to 4.5 µg/dl. Her case was a usual presentation of ICI-mediated secondary AI as it occurred within 1-2 months of stopping ICI therapy. Conclusion: As we continue to learn about ICI-mediated endocrinopathies, it is imperative to document the variation in timing of presentation. ICI-mediated hypophysitis can present at any time after the initiation of therapy. Given this variation, there is need for routine screening and early treatment of hypophysitis to reduce ED visits and readmission rates.

Life-Threatening VIPoma Crisis in an Immunocompromised Patient

Background: Vasoactive intestinal peptide-secreting tumors (VIPoma) are rare neuroendocrine tumors (NETs) that present with a triad of profuse watery diarrhea, hypokalemia, and achlorhydria. The resulting renal impairment, electrolytes and acid-base imbalances pose a high risk of morbidity and mortality. We describe a case of life-threatening VIPoma crisis in an immunocompromised patient. Clinical Case: A 64-year-old man was intubated after he was brought in unconscious with tachypnea. Upon review, he had experienced persistent watery diarrhea for the past 6 months, with a weight loss of 18 kg. He had severe hypokalemia (potassium 1.9 mmol/L, n= 3.5-5.0), metabolic acidosis (blood gases pH 6.927, bicarbonate 4.8 mmol/L, base excess -25.9 mmol/L), and acute kidney injury (urea 47.9 mmol/L, creatinine 980umol/L). He continued to have electrolyte imbalances and acidosis due to persistent diarrhea, despite hydration and dialysis support. His biohazard screening results were positive for human immunodeficiency virus (HIV), with a CD4 count of 101 cells/µl. He was given courses of antibiotics for treating pathogenic infections; however, his septic workups were negative for infection, including HIV-related opportunistic infections. Later, pancreatic CT revealed a well-defined heterogeneously enhancing pancreatic head mass, size 6.8x5.2x7.5 cm. Further laboratory investigations confirmed the diagnosis of VIPoma, with elevated VIP levels (1600 pg/ml, n < 75). Eventually, subcutaneous octreotide was started, with resolution of the diarrhea and normalization of his electrolytes and renal function. After a 6-week hospital stay, he was discharged well with monthly octreotide and initiated on antiretroviral therapy (ART). After 3 months of ART, his CD4 count improved, and he remained diarrhea-free with octreotide. He is scheduled for tumor debulking surgery. Conclusion:This case highlights the importance of having a clinical suspicion of NETs, especially in immunocompromised patients. Further investigations and imaging studies to rule out noninfectious pathologies should be considered in patients who respond poorly to standard therapy. In VIPoma, somatostatin analog is an antisecretory treatment and it is highly effective for controlling diarrhea. High-dose octreotide up to 1500 µg/day has previously been studied for treatment of refractory diarrhoea in the setting of HIV infection² and it has been found to be helpful in reducing stool volume and frequency. Lastly, delays in the diagnosis and treatment of VIPoma in immunocompromised patients can be fatal. References1/ Hoffland J., Kaltsas G., de Herder W. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocrine Reviews, Volume 41, Issue 2, April 2020, Pages 371-403.2/ Farthing MJ. Octreotide in the treatment of refractory diarrhoea and intestinal fistulae. Gut 1994;35:S5-10.

Effects of SLC protein on intestinal HCO&amp;lt;sup&amp;gt;-&amp;lt;/sup&amp;gt;&amp;lt;sub&amp;gt;3&amp;lt;/sub&amp;gt; excretion and acid-base balance of &amp;lt;italic&amp;gt;Gymnocypris przewalskii&amp;lt;/italic&amp;gt;

Saline-alkaline water, widely distributed throughout China, is characterized as high salinity and alkalinity, which are the primary factors restricting the survival and growth of aquatic organisms. The physiological mechanisms required for fish to live in fresh water and sea water are well described for several species. Many fishes not only can tolerate, but also can acclimate and adapt to conditions besides conventional fresh water and sea water conditions, specifically saline-alkaline water. When fishes are transferred to saline-alkaline water, there is a transient alkalosis with increased HCO^-₃ or decreased <italic>P</italic>_CO₂ concentrations in the plasma. <italic>Gymnocypris przewalskii</italic> is the most important economic fish in Lake Qinghai, a water body with high salinity and alkalinity. In recent years, the population of <italic>G</italic>. <italic>przewalskii</italic> has sharply declined due to the destruction of spawning habitat, long-term overfishing and the increasing salinity and alkalinity. Thus, researches on the physiological and molecular responses of <italic>G</italic>.<italic>przewalskii</italic> under saline-alkaline conditions are significant for recovering this endangered species. Previous studies had shown that, when <italic>G</italic>. <italic>przewalskii</italic> was acclimated to saline-alkaline water, internal excess HCO^-₃ was not totally excreted by the gills or the kidney. In contrast, it showed that intestinal HCO^-₃ secretion and water absorption might play important roles in the acid-base balance and osmoregulation. In order to explore the effects of SLC protein on intestinal HCO^-₃ excretion and acid-base regulation, <italic>Gymnocypris przewalskii</italic> was exposed to fresh water and saline-alkaline lake water treatments. 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate (DIDS) was injected to control the activity of SLC protein, the intestinal HCO^-₃ excretion concentration, blood physiological indices, and the relative expression of <italic>SLC</italic>4<italic>A</italic>1, <italic>SLC</italic>4<italic>A</italic>2, <italic>SLC</italic>4<italic>A</italic>4, <italic>SLC</italic>26<italic>A</italic>6 genes in the intestine of <italic>Gymnocypris przewalskii</italic> were detected. Results showed that under saline-alkaline environment, the blood pH of <italic>Gymnocypris przewalskii</italic> increased significantly, while the <italic>P</italic>_CO₂ decreased, the concentration of intestinal HCO^-₃ excretion and the expression levels of <italic>SLC</italic>4<italic>A</italic>1, <italic>SLC</italic>4<italic>A</italic>4, and <italic>SLC</italic>26<italic>A</italic>6 genes increased significantly. After the injection of DIDS, the blood pH and HCO^-₃ concentration of <italic>Gymnocypris przewalskii</italic> in the fresh water group increased significantly while <italic>P</italic>_CO₂ decreased; in saline-alkaline water group, the blood pH and HCO^-₃ concentration of <italic>Gymnocypris przewalskii</italic> increased significantly, and the intestinal HCO^-₃ excretion concentration declined. Results indicated that <italic>Gymnocypris przewalskii</italic> intestinal HCO^-₃ excretion in saline-alkaline environment increased, but the excretion declined with the inhibition of SLC family proteins, leading to blood pH increase and acid-base imbalance. This study indicate that the SLC family protein may play a compensatory role in the adaptation of <italic>Gymnocypris przewalskii</italic> to high saline-alkaline environment.

Usefulness of Osmolar Excretion Rate in the Diagnosis of Fluids and Electrolytes Overlap Syndromes

Clinical practice related to electrolytes and acid-base disorders is commonly approached as a single entity. Overlap syndromes are an uncommon clinical condition that must be considered as part of differential diagnosis when a patient is assessed. The coexistence of electrolytic disorders could make it difficult to interpret certain variables due to the influence of such disorders on the same variable, even in the opposite way. In this context, there are some tools that are very useful in order to establish the correct diagnosis. Thus, osmole excretion rate, tonicity balance, and estimation of electrolyte-free water balance should be considered along with other biochemical variables in order to increase the possibility to make a correct interpretation.

Exchange Protein Directly Activated by cAMP Isoform 2 (Epac2) but Not Isoform 1 (Epac1) Is Critical for Renal Acid‐Base Handling

Cyclic adenosine monophosphate (cAMP) is a critical second messenger of numerous systemic and local signals affecting water-electrolyte transport and pH regulation by the renal tubule. Exchange proteins directly activated by cAMP (Epacs) are guanine nucleotide exchange factors commonly operating independently from the classical cAMP-protein kinase A (PKA) signaling. We previously demonstrated that both Epac isoforms, namely Epac1 and Epac2 are functionally expressed in the proximal tubule and the collecting duct. Epac1 -/- and Epac2 -/- mice exhibit urinary concentrating defect and salt wasting in response to hypovolemia. Since the proximal tubule and the collecting duct are central for urinary acid/base excretion, we examined the role of Epac1 and Epac2 in maintaining systemic pH balance. EpacWT, Epac1-/-, and Epac2 -/- mice had comparable arterial pH of 7.33±0.02, 7.33±0.04, and 7.30±0.02 respectively at the baseline. However, urinary pH was significantly lower only in Epac2 -/- (5.96±0.06), but not Epac1 -/- (6.61±0.15) when compared to EpacWT (6.90±0.38). Acid loading with NH4Cl supplementation in water for 3 days mildly reduced arterial pH in EpacWT and Epac1-/- to 7.27±0.01 and 7.24±0.03 respectively, but induced significantly greater acidosis (7.12±0.03) in Epac2 -/- mice. This was also associated with significantly lower blood HCO3- levels in Epac2 -/- compared to Epac1-/- and EpacWT: 18±1 mM/l, 23±2 mM/l, and 23±1 mM/l, respectively. Furthermore, NH4Cl supplementation led to marked reduction in urinary pH levels of EpacWT and Epac1-/-, but failed to significantly decrease already low urinary pH in Epac2 -/- (5.86±0.03). While NHE-3 levels in the proximal tubule were significantly reduced in Epac1-/-mice (~50%), this was more pronounced in Epac2-/- mice (~90%). Furthermore, pHi analysis in freshly isolated split-opened collecting ducts revealed altered recovery after acidification in intercalated cells of Epac2-/- mice. Overall, we report that Epac2 plays a critical role in renal adaptation to acidification. Epac2 deficiency compromises urinary acid excretion by reducing NHE-3 expression in the proximal tubule and distorting titratable acid excretion by the collecting duct intercalated cells leading to severe acidosis. In contrast, Epac1 does not play a major role in renal acid/base handling. The observed reduction in NHE-3 levels in Epac1-/- are effectively compensated by the acid excretion in the collecting duct and thus does not lead to prominent alteration in blood pH. We speculate that pharmacology-based manipulation with Epac2, but not Epac1 might be of relevance in managing acid-base disorders in the clinical setting.

The influence of hydrogen ions on coagulation in traumatic brain injury, explored by molecular dynamics

ABSTRACT Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition. Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests. Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten “healthy control subjects”, and another nine patients as “disease control subjects”; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules. Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in “disease control subjects”. Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors “trap” ions. Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.

Особливості інтенсивної терапії у хворих на діабетичний кетоацидоз у період пандемії COVID-19

У статті аналізуються механізми розвитку та клінічні прояви діабетичного кетоацидозу (ДКА), надано програму інтенсивної терапії, обговорюються перспективи застосування інфузійних засобів на основі ксилітолу в лікуванні ДКА. Автори надали власний досвід застосування розчину з 5% вмістом ксилітолу. Було показано, що застосування ксилітолу дозволяє позитивно впливати на різні ланки патологічного процесу — від усунення дегідратації до корекції порушень кислотно-лужного стану. Автори також обговорюють причини виникнення тяжкого кетоацидозу у хворих на COVID-19 та наводять власний досвід лікування 14 пацієнтів із ДКА на фоні COVID-19.

Association Between Respiratory Alkalosis and the Prognosis of COVID-19 Patients.

Aim: The aim of the study was to describe the clinical characteristics of patients with or without respiratory alkalosis, and analyze the relationship of respiratory alkalosis and the outcome of adult coronavirus disease 2019 (COVID-19) patients.Methods: Clinical and laboratory data of adult COVID-19 patients in a single center in China, were retrospectively collected and analyzed. The Kaplan-Meier (KM) curve and cox regression were adopted to analyze the association between respiratory alkalosis and prognosis of COVID-19 patients.Results: Of 230 adult COVID-19 patients, 66 patients (28.7%) had respiratory alkalosis on admission. Of 66 patients, the median age was 53 years old (range, 21–84 years), and 43 (65.2%) were female. Compared with those without respiratory alkalosis, patients with respiratory alkalosis were significantly older (P = 0.002), had a higher proportion of female (P = 0.004), and showed higher ratios of underlying diseases including hypertension (P = 0.023) and cardiovascular disease (P = 0.028). Moreover, they demonstrated higher proportion of severe events (P = 0.001). Patients with respiratory alkalosis had a higher possibility of developing severe events compared with those without respiratory alkalosis (Log Rank P = 0.001). After adjusting for gender, age, and comorbidities, patients with respiratory alkalosis still showed significantly elevated risks of developing to severe cases (HR 2.445, 95% CI 1.307–4.571, P = 0.005) using cox regression analyses.Conclusions: Respiratory alkalosis as a common acid—base disorder in COVID-19 patients, was associated with a higher risk of developing severe event.

Metabolic acidosis in neobladder patients : Risk factors and treatment options

In cystectomy patients who underwent neobladder creation, the intestinal mucosa of the neobladder is in constant contact with urine, which may result in chronic metabolic acidosis (CMA) due to specific absorption capabilities of the intestinal mucosa. Despite being aprevalent comorbidity, the risk factors for CMA and its diagnostic parameters are poorly understood. This review examines the risk factors associated with the development of CMA and their prevalence in patients with aneobladder. We conducted asystematic literature search using the PubMed database to detect studies about the topics CMA and neobladder that were published between 2000 and 2020. The prevalence and risk factors for CMA in neobladder patients were assessed by reviewing 23studies. Acidosis is most prevalent during the first year after surgery (25-70%). Risk factors are renal failure, high continence, old age and diabetes mellitus. The prevalence of CMA is at its highest during the early postoperative period for neobladder patients, so for this time period, weekly diagnostic investigations are recommended according to the German S3-guidelines for the "Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinomsent für Neoblasepatienten". Blood gas tests should not only be used to analyze the pH value but also to detect and counteract acid-base imbalance issues in time. The recommended normalization of serum bicarbonate levels with oral bicarbonate follows patient-specific therapy strategies.

ABG Assistant-Towards an Understanding of Complex Acid-Base Disorders.

The ability to diagnose acid-base imbalances correctly is essential for physicians and other healthcare workers. Despite its importance, it is often considered too complex and confusing. Although most people dealing with arterial blood gases (ABGs) do not usually have problems with acid-base disorder assessment, such an analysis is also carried out by other healthcare workers for whom this can be a challenging task. Many aspects may be problematic, partly due to multiple data analysis methods and no definitive statement on which one is better. According to our survey, the correctness of arterial blood gas analysis is unsatisfactory, especially in mixed disorders, which do not always manifest an obvious set of symptoms. Therefore, ABG parameters can be used as an established biomarker panel, which is considered to be a powerful tool for personalized medicine. Moreover, using different approaches to analyze acid-base disorders can lead to varying diagnoses in some cases. Because of these problems, we developed a mobile application that can spot diagnostic differences by taking into account physiological and chemical approaches, including their variants, with a corrected anion gap. The proposed application is characterized by a high percentage of correct analyses and can be an essential aid for diagnosing acid-base disturbances.

POS-004 HYPOALBUMINEMIA AND ACUTE KIDNEY INJURY IN PATIENTS ADMITTED TO INTENSIVE CARE UNIT

Acute kidney injury (AKI) is a disease of diverse etiology, consisting of a decrease in the glomerular filtration rate and therefore with the retention of waste products such as urea and creatinine, accompanied by fluid, electrolyte and acid-base disorders. It is present in 39.5% of the cases admitted to intensive care unit (ICU) in our hospital, it affects mainly men with infectious processes, impacting mortality. Hypoalbuminemia has been associated with positive fluid balances, however there are few studies that attempt to associate it with AKI. Case-control study, including patients admitted to ICU at Hospital Central Sur de Alta Especialidad (HCSAE) in Mexico City with serum albumin determination at admittance. The cases were distributed into a control group (normoalbuminemia >3.5 g/dl) and the studied group (hypoalbuminemia <3.5 g/dl). Patients on hemodialysis, peritoneal dialysis, kidney transplant, burned patients, fed by parental nutrition, and patients with liver failure were excluded. Those patients who presented two AKI events in less than 7 days were eliminated. Statistical analysis was carried out using SPSS software, version 20 (SPSS, Inc., Chicago, IL). A t-test and one-way ANOVA were used for analysis of normally distributed data. Categorical data were compared using a Pearson chi-squared test or Fisher’s exact test. Data that were not normally distributed were analyzed using a Mann–Whitney U test, Wilcoxon signed-rank test, and Kruskal–Wallis test. Continuous variables were described using mean standard deviation or median with interquartile range (IQR). P values ≤ 0.05 were considered to represent statistically significant differences. The primary outcome was to determine whether hypoalbuminemia is associated with development of AKI in patients admitted to ICU. 197 patients were included, 174 in the group to study and 23 for the control group; men (51%) ,median age was 71 (+17.41) years. Mortality predominated in the study group with 160 (92%) vs 16 (69.6%) for the control (p <0.005). The outcome of AKI was more frequent in patients with hypoalbuminemia with 122 (70.1%) cases compared to the control (39.1%) and OR 3.01 [95% CI 1.48-8.9; p = 0.004),septic shock with was present in 54% in patients with hypoalbuminemia (p <0.0001). Hypoalbuminemic patients had higher amine requirements compared to the control group [132 (75.9%); p = 0.001]. The ratio in patients with acute kidney injury versus not AKI is 3.01 higher in patients with hypoalbuminemia.

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

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. 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. 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. 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.

Study of Respiratory System Response During Decompression of a Pressurized Compartment.

The paper presents a solution for modeling the dynamics of human gas ex-change indicators in space flight based on a static model of the respiratory sys-tem, taking into account the peculiarities of gas exchange process. The paper also describes a computational experiment which was carried out to simulate indicators during ascent, demonstrating the capabilities of the model to predict the state of the respiratory system. The simulation results show that a decrease in the total barometric pressure leads to the respiratory capacity changes: the volume of the alveolar space decreases and the tidal dead space volume in-creases in the ratio from 4.7 to 0.7. A noncompensated respiratory alkalosis leading to the acid-base disorders develops as well. The computational experi-ment applied under the considered methodological approach allows studying the problems related to the flight safety and risk management under various operating modes of life support systems.

Stewart (physicochemical) approach versus conventional anion gap approach for resolution of metabolic acidosis in diabetic ketoacidosis

Diabetic ketoacidosis (DKA) frequently requires emergency admission. The anion gap approach is conventionally used for the diagnosis and documenting the resolution of acidosis during treatment. However, it fails to detect hyperchloremic acidosis during the resolution and may result in the prolongation of treatment. To determine the role of the Stewart approach of acid-base disorder during DKA management for the prediction of an earlier resolution. A prospective comparative study was conducted between January 2017 and December 2017 at a single academic hospital in north India. Patients aged above 12 years with a diagnosis of DKA were randomly divided into two groups—the conventional group and the Stewart group, according to the approach used for DKA resolution. The primary outcome was the time duration required for resolution. The secondary outcomes were the therapeutic requirement of intravenous fluid, insulin, and potassium, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the time of resolution, and hospital stay. Forty-four DKA patients were equally distributed in the two groups with comparable baseline parameters. The Stewart group had early resolution of DKA (mean, 32.4±17.5 h versus 41.7±19.6 h; p value <0.001) at similar APACHE II scores. The duration of hospital stay was reduced but was not statistically significant (mean, 5.6±3.2 days versus 7.0±3.8 days; p value 0.16). The therapeutic requirement of fluid, insulin, and potassium was similar in groups. The Stewart approach may be a better alternative to the conventional anion gap approach for guiding the resolution of DKA.

INFLUENCE OF VARIOUS FACTORS ON THE FREQUENCY OF COMPLICATIONS IN SKELETAL POLYTRAUMA AFTER INTERHOSPITAL TRANSPORT AND AT THE INTENSIVE CARE UNIT

The study involved 240 patients with skeletal polytrauma. The aim of the study was to improve the results of treatment of victims with skeletal polytrauma by substantiating methods for predicting and preventing various complications after interhospital transportation and in the intensive care unit. We found that after interhospital transportation of patients, the following complications were detected: fatty embolism (11.6%), anemic syndrome (51.7%), acute respiratory failure (20.3%), pneumonia (13.4%). The main defects at the hospital stage were: incomplete laboratory and instrumental studies (81.7%), untimely surgical osteosynthesis (49.2%), undiagnosed complications (31.2%), underestimation of the severity of the condition (30%), inadequate correction of hypovolemia, anemic syndrome, coagulopathy (51.7%, 81.7%, 63.3%, respectively), inadequate prevention of thromboembolic complications and fatty embolism (70%, 51.7%), inadequate correction of acid-base disorders and dyselectrolytemia (100%).

Hypertonic saline solution decreases oxidative stress in liver hypothermic ischemia

BackgroundLiver ischemia reperfusion injury is still an unsolved problem in liver surgery and transplantation. In this setting, hypothermia is the gold standard method for liver preservation for transplantation. Hypertonic saline solution reduces inflammatory response with better hemodynamic recovery in several situations involving ischemia reperfusion injury. Here, we investigated the effect of hypertonic saline solution in hypothermic liver submitted to ischemia reperfusion injury. MethodsFifty male rats were divided into 5 groups: SHAM, WI (animals submitted to 40 minutes of partial warm liver ischemia and reperfusion), HI (animals submitted to 40 minutes hypothermic ischemia), HSPI (animals submitted to hypothermic ischemia and treated with 7.5% hypertonic saline solution preischemia), and HSPR (animals submitted to hypothermic ischemia and treated with hypertonic saline solution previously to liver reperfusion). Four hours after reperfusion, the animals were euthanized to collect liver and blood samples. ResultsAspartate aminotransferase and alanine aminotransferase, histologic score, and hepatocellular necrosis were significantly decreased in animals submitted to hypothermia compared with the warm ischemia group. Malondialdehyde was significantly decreased in hypothermic groups with a further decrease when hypertonic saline solution was administrated preischemia. Hypothermic groups also showed decreased interleukin-6, interleukin-10, and tumor necrosis factor-α concentrations and better recovery of bicarbonate, base excess, lactate, and glucose blood concentrations. Moreover, hypertonic saline solution preischemia was more effective at controlling serum potassium concentrations. ConclusionHypertonic saline solution before hypothermic hepatic ischemia decreases hepatocellular oxidative stress, cytokine concentrations, and promotes better recovery of acid-base disorders secondary to liver ischemia reperfusion.

Ocean acidification compromises energy management in Sparus aurata (Pisces: Teleostei)

The effects of ocean acidification mediated by an increase in water pCO2 levels on marine organisms are currently under debate. Elevated CO2 concentrations in the seawater induce several physiological responses in teleost fish, including acid-base imbalances and osmoregulatory changes. However, the consequences of CO2 levels enhancement on energy metabolism are mostly unknown. Here we show that 5 weeks of exposure to hypercapnia (950 and 1800 μatm CO2) altered intermediary metabolism of gilthead seabream (Sparus aurata) compared to fish acclimated to current ocean values (440 μatm CO2). We found that seabream compromises its physiological acid-base balance with increasing water CO2 levels and the subsequent acidification. Intestinal regions (anterior, mid, and rectum) engaged in maintaining this balance are thus altered, as seen for Na+/K+-ATPase and the vacuolar-type H+-ATPase activities. Moreover, liver and muscle counteracted these effects by increasing catabolic routes e.g., glycogenolysis, glycolysis, amino acid turnover, and lipid catabolism, and plasma energy metabolites were altered. Our results demonstrate how a relatively short period of 5 weeks of water hypercapnia is likely to disrupt the acid-base balance, osmoregulatory capacity and intermediary metabolism in S. aurata. However, long-term studies are necessary to fully understand the consequences of ocean acidification on growth and other energy-demanding activities, such as reproduction.

A simplified protocol for individualized regional citrate anticoagulation for hemodialysis: A single-center, randomized clinical study.

The lack of individualized treatment protocols and complicated procedures are important factors limiting the use of regional citrate anticoagulation (RCA) technology in hemodialysis. This study aims to validate the safety and efficacy of a simplified individualized RCA protocol for hemodialysis. From June 2019 to August 2019, 45 patients with active bleeding or bleeding tendency undergoing maintenance hemodialysis in the Nephrology Department of the First Affiliated Hospital of Nanchang University were randomly divided into a modified conventional RCA protocol group with a low-flux dialyzer, a simplified individualized RCA protocol group with a high-flux dialyzer, and a simplified individualized RCA protocol group with a low-flux dialyzer. A total of 45 patients were included in this study. The mean age of the patients was 57.38 ± 19.05 years, and 78% were men. Forty-three patients completed 4 hours of hemodialysis, and the median total clotting scores in the 3 groups were 11, 12, and 12. Compared with the modified conventional RCA protocol group with a low-flux dialyzer, the 2 simplified individualized RCA protocol groups had better clotting scores for the dialyzer, arterial bubble trap, and single-pool urea clearance index (spKt/VBUN) and lower costs. Moreover, these parameters did not differ between the 2 simplified individualized RCA protocol groups. No electrolyte or acid-base imbalances or citrate poisoning was observed in any of the 3 groups. Adverse events did not differ significantly among the 3 groups. The simplified individualized RCA protocol is safe, effective, and easy to implement. Therefore, this protocol can be promoted for clinical practice. This study was registered in the Chinese Clinical Study Registry under registration number ChiCTR1900023801.