A basic solution for a complex problem: does treatment of metabolic acidosis slow CKD progression?

PURPOSE OF THIS REVIEW: Metabolic acidosis is frequently encountered in patients with chronic kidney disease (CKD), with increasing prevalence as kidney function worsens. Treating electrolyte disturbances is the sine qua non of Nephrologists, and alkali therapy to normalize serum bicarbonate levels and slow progression of kidney disease has been embedded in clinical practice guidelines for decades on the basis of animal models and controversial clinical trials. This review will critically appraise the literature base for this recommendation and determine whether the available evidence supports this common practice, which is a timely endeavor considering the impending demotion of metabolic acidosis treatment from recommendation to practice point in forthcoming KDIGO guidelines. RECENT FINDINGS: Earlier, open-label, studies supporting the utility of sodium bicarbonate therapy to slow progression of chronic kidney disease have been challenged by more recent, blinded, studies failing to show benefit on CKD progression. This was further demonstrated in the absence of concomitant sodium administration with the hydrochloric acid binder veverimer, which failed to demonstrate benefit on renal death, end stage kidney disease or 40% reduction in estimated glomerular filtration rate in a large multicenter trial. SUMMARY: The current body of literature does not support the routine treatment of metabolic acidosis in patients with CKD and the authors agree with the forthcoming KDIGO guidelines to de-emphasize this common practice.

Arterial Blood Gases and Acid-Base Regulation.

Disorders of acid-base status are common in the critically ill and prompt recognition is central to clinical decision making. The bicarbonate/carbon dioxide buffer system plays a pivotal role in maintaining acid-base homeostasis, and measurements of pH, PCO2, and HCO3 - are routinely used in the estimation of metabolic and respiratory disturbance severity. Hypoventilation and hyperventilation cause primary respiratory acidosis and primary respiratory alkalosis, respectively. Metabolic acidosis and metabolic alkalosis have numerous origins, that include alterations in acid or base intake, body fluid losses, abnormalities of intermediary metabolism, and renal, hepatic, and gastrointestinal dysfunction. The concept of the anion gap is used to categorize metabolic acidoses, and urine chloride excretion helps define metabolic alkaloses. Both the lungs and kidneys employ compensatory mechanisms to minimize changes in pH caused by various physiologic and disease disturbances. Treatment of acid-base disorders should focus primarily on correcting the underlying cause and the hemodynamic and electrolyte derangements that ensue. Specific therapies under certain conditions include renal replacement therapy, mechanical ventilation, respiratory stimulants or depressants, and inhibition of specific enzymes in intermediary metabolism disorders.

Electrolytes disturbances in cancer patients.

PURPOSE OF REVIEW: Hypernatremia, hyperphosphatemia, hypocalcaemia, hyperkalaemia and hypermagnesemia are electrolytes disturbances that can arise in cancer patients in relation to unique causes that are related to the cancer itself or its treatment and can lead to delay or interruption of cancer therapy. This article summarizes these main causes, the proposed pathophysiology and the recommended management for these disturbances. RECENT FINDINGS: There have been many cancer drugs approved in the field of oncology over the past several years and a subset of these drugs have been associated with electrolytes disturbances. This includes, for example, immune checkpoint inhibitor related hyperkalemia, fibroblast growth factor 23 inhibitor associated hyperphosphatemia and epidermal growth factor receptor inhibitor associated hypomagnesemia and hypocalcaemia. SUMMARY: This article provides an updated review of certain electrolytes disturbance in cancer patients and allows clinicians to have a greater awareness and knowledge of these electrolyte abnormalities in efforts to early recognition and timely management.

Bloodstream Infections in Preterm Neonates and Mortality-Associated Risk Factors.

OBJECTIVE: To investigate the association of early (±4 hours after onset of bloodstream infection) clinical and laboratory variables with episode-related mortality (<7 days). STUDY DESIGN: This 2-site retrospective study included 142 neonates born at <35 weeks of gestational age with positive blood/cerebrospinal fluid (CSF) culture at >72 hours of age from organisms other than coagulase-negative Staphylococcus. Early variables were compared between those with bloodstream infection-related mortality and survivors. Multivariable analysis was conducted for the primary outcome, and the area under the curve (AUC) was estimated for relevant variables. RESULTS: The neonates who died were of lower gestational age at disease onset. After adjusting for relevant variables, lowest mean blood pressure (MBP) (aOR, 0.10; 95% CI, 1.02-1.19) and highest base deficit (aOR, 1.18; 95% CI, 1.06-1.32) were independently associated with mortality. The AUC was 0.87 (95% CI, 0.78-0.96) for base deficit, increasing to 0.91 (95% CI, 0.83-0.99) with the addition of MBP. CONCLUSION: Low MBP and high base deficit within ±4 hours of bloodstream infection onset identify preterm neonates at risk of mortality.

Fluid management in chronic kidney disease: what is too much, what is the distribution, and how to manage fluid overload in patients with chronic kidney disease?

PURPOSE OF REVIEW: Assessment of fluid status to reach normovolemia in patients with chronic kidney disease (CKD) continues to be a tough task. Besides clinical observation, technological methods have been introduced, yet, the best approach is still uncertain. The present review looks at fluid overload in CKD from three perspectives: the critical fluid threshold leading to adverse cardiovascular outcomes, fluid distribution and its clinical correlates, and direct effect of fluid overload on vascular function related to disturbance of the sodium-skin axis and endothelial glycocalyx dysfunction. RECENT FINDINGS: To determine fluid status, both the absolute and relative fluid overload is used as parameter in clinical practice. In addition, the definition of fluid overload is ambivalent and its relation to symptom burden has not been studied well. Studies on the impact of distribution of fluid are scarce and the limited evidence suggests differences based on the cause of CKD. So far, no standardized technologies are available to adequately determine fluid distribution. After discovering the 'third compartment' of total body sodium in skin and muscle tissue and its potential direct effect on vascular function, other biomarkers such as VEGF-C are promising. SUMMARY: We propose a multimodal clinical approach for volume management in CKD. Because there are currently no studies are available demonstrating that correction of fluid overload in CKD will lead to better outcome, these are strongly needed.

Assessing Acid-Base Status in Circulatory Failure: Relationship Between Arterial and Peripheral Venous Blood Gas Measurements in Hypovolemic Shock.

BACKGROUND AND OBJECTIVES: In severe circulatory failure agreement between arterial and mixed venous or central venous values is poor; venous values are more reflective of tissue acid-base imbalance. No prior study has examined the relationship between peripheral venous blood gas (VBG) values and arterial blood gas (ABG) values in hemodynamic compromise. The objective of this study was to examine the correlation between hemodynamic parameters, specifically systolic blood pressure (SBP) and the arterial-peripheral venous (A-PV) difference for all commonly used acid-base parameters (pH, Pco 2, and bicarbonate). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Data were obtained prospectively from adult patients with trauma. When an ABG was obtained for clinical purposes, a VBG was drawn as soon as possible. Patients were excluded if the ABG and VBG were drawn >10 minutes apart. RESULTS: The correlations between A-PV pH, A-PV Pco 2, and A-PV bicarbonate and SBP were not statistically significant (P = .55, .17, and .09, respectively). Although patients with hypotension had a lower mean arterial and peripheral venous pH and bicarbonate compared to hemodynamically stable patients, mean A-PV differences for pH and Pco 2 were not statistically different (P = .24 and .16, respectively) between hypotensive and normotensive groups. CONCLUSIONS: In hypovolemic shock, the peripheral VBG does not demonstrate a higher CO2 concentration and lower pH compared to arterial blood. Therefore, the peripheral VBG is not a surrogate for the tissue acid-base status in hypovolemic shock, likely due to peripheral vasoconstriction and central shunting of blood to essential organs. This contrasts with the selective venous respiratory acidosis previously demonstrated in central venous and mixed venous measurements in circulatory failure, which is more reflective of acid-base imbalance at the tissue level than arterial blood. Further work needs to be done to better define the relationship between ABG and both central and peripheral VBG values in various types of shock.

Spironolactone-furosemide combination therapy and acid-base disorders in liver cirrhosis patients
.

OBJECTIVE: Respiratory alkalosis (RA) and dilutional hyperchloremic acidosis (DHA) are the most common acid-base balance (ABB) disorders in patients with liver cirrhosis. The aims of this study were to clarify whether RA develops in relation to DHA via respiratory compensation of metabolic acidosis and whether spironolactone in combination with low-dose furosemide - diuretics known to ameliorate DHA - positively affects RA in liver cirrhosis patients. MATERIALS AND METHODS: 59 patients with advanced cirrhosis were divided into two groups. Group D consisted of individuals (urine sodium concentration (UNa+) > 20 mmol/L) who responded to combination therapy consisting of spironolactone and low-dose furosemide. The non-D group consisted of individuals (UNa+ ≤ 20 mmol/L) who either did not respond to the treatment or who were not administered it. In both groups, we examined serum and urine concentrations of electrolytes and ABB parameters, including SNa+-SCl- and SNa+/SCl- values. RESULTS: In group D, we found a statistically significant relationship between pCO2 and SHCO3-: r = 0.756 (p < 0.001) and between pCO2 and SNa+-SCl-: r = 0.522 (p = 0.001). Neither Salb nor the corrected anion gap were associated with changes in SHCO3- or pCO2 values. Although SHCO3- values were normal, abnormal pCO2 values were observed in one third of group D patients. Based on multivariable analysis, SHCO3- proved to be a statistically significant influencing factor on pCO2 values. CONCLUSION: DHA contributes to the development of RA in individuals with liver cirrhosis. Reducing DHA by means of effective diuretic therapy comprising spironolactone and furosemide has a beneficial effect on RA in such patients.

Spuriously Low Serum Bicarbonate Levels in Patients With Hyperlipidemia: A Report of 4 Cases.

Four patients were recently seen at our institution presenting with severe hypobicarbonatemia and elevated anion gap on serum specimens processed by an autoanalyzer using enzymatic reactions. Arterial blood gas values in each case revealed no significant acid-base disturbance and a marked discordance between arterial blood gas calculated bicarbonate levels and those reported on the basic metabolic panel. All patients had profound hyperlipidemia (triglycerides > 3,500mg/L), and ultracentrifugation of one patient's serum corrected the discordance. Lipid interference with the photometric measurement of light absorbance after enzymatic reaction in the autoanalyzer is thought to be responsible for the low reported bicarbonate values. Use of an indirect ion-specific electrode method for total carbon dioxide analysis would avoid this pitfall. Caution is advised when enzymatic autoanalyzer-calculated laboratory values are used to diagnose acid-base disturbances in patients with severe hyperlipidemia. Physicians involved in the diagnosis of acid-base disorders in hospitalized patients should always be aware of the method used by their chemistry laboratories to determine total carbon dioxide values.

Retarding progression of chronic kidney disease: use of modalities that counter acid retention.

PURPOSE OF REVIEW: Acid retention because of chronic kidney disease (CKD) increases tissue acidity and accelerates progression of CKD, whereas reduction in acid retention slows progression of CKD. Herein, we describe the mechanisms through which increased tissue acidity worsens CKD, modalities for countering acid retention and their impact on progression of CKD, and current recommendations for therapy. RECENT FINDINGS: Studies in animals and humans show that increased tissue acidity raises the renal levels of endothelin, angiotensin II, aldosterone, and ammoniagenesis, thereby worsening renal fibrosis and causing progression of CKD. Measures that counter acid retention, such as providing alkali or modifying the quantity or type of dietary protein, reduce the levels of endothelin, angiotensin II, aldosterone, and ammoniagenesis, slowing progression of CKD. Alkali can be provided as NaHCO3, sodium citrate, or base in fruits and vegetables. A serum [HCO3] of 24-26 mEq/l is targeted, because higher values can be associated with adverse consequences. SUMMARY: Insights into the mechanisms through which increased tissue acidity mediates progression of CKD and the beneficial impact of ameliorating positive acid balance underlie our recommendation for modalities that counter acid retention in CKD.

Hyperchloremia and postoperative acute kidney injury: a retrospective analysis of data from the surgical intensive care unit.

BACKGROUND: Whether perioperative hyperchloremia can induce postoperative acute kidney injury (AKI) is controversial. We investigated the association between perioperative hyperchloremia and postoperative AKI in patients admitted to the intensive care unit (ICU) after surgery. METHODS: We performed a retrospective observational study of patients admitted to the surgical ICU at a single tertiary care hospital between January 2011 and June 2016. Our primary objective was to determine whether hyperchloremia or an increase in serum chloride levels was associated with postoperative AKI. Perioperative hyperchloremia was defined as serum chloride levels ≥ 110 mmol·L- 1 during postoperative days (PODs) 0-3. The increase in serum chloride levels was defined as the difference between preoperative and maximum postoperative serum chloride levels during the first 3 days after surgery. RESULTS: Of the 7991 patients included in the final analysis, 1876 (23.5%) developed hyperchloremia during PODs 0-3, and 1187 (14.9%) developed postoperative AKI. Exposure to hyperchloremia during the first 3 days after surgery was not associated with postoperative AKI (odds ratio, 1.09; 95% confidence interval, 0.80-1.49; P = 0.571). However, among patients with preoperative chronic kidney disease stage ≥ 3 (estimated glomerular filtration rate < 60 mL·min- 1·1.73·m- 2), the incidence of postoperative AKI was higher in patients with an increase > 6 mmol·L- 1 in serum chloride levels than in patients with an increase ≤ 1 mmol·L- 1 (odds ratio, 1.42; 95% confidence interval, 1.09-1.84; P = 0.009). In addition, the incidence of postoperative AKI stage ≥ 2 was not associated with exposure to hyperchloremia or with the increase in serum chloride levels during PODs 0-3, regardless of preoperative kidney function. CONCLUSIONS: Exposure to perioperative hyperchloremia is not associated with postoperative AKI in surgical ICU patients. However, in patients with moderate-to-severe chronic kidney disease (stage ≥ 3), a substantial perioperative increase in serum chloride levels may reflect a higher risk of AKI.

Beyond bicarbonate: complete acid-base assessment in patients receiving intermittent hemodialysis.

Background: Acid-base assessments in hemodialysis patients have been limited almost entirely to measurements of total CO 2 concentration, and assumptions have been made about the presence of acid-base disorders. To gain a fuller understanding of the acid-base status of stable hemodialysis patients, we analyzed measurements of pCO 2 , pH and HCO 3 - obtained in a cohort of chronic stable hemodialysis patients over a 5-year period. Methods: We reviewed acid-base measurements taken pre-dialysis from fistula blood in 53 outpatients receiving hemodialysis thrice weekly between 2008 and 2012. In these patients, pH and pCO 2 were measured using an onsite blood gas analyzer, and HCO 3 - was computed. Relevant clinical and laboratory data were obtained from medical records. Factors affecting serum HCO 3 - were identified. Simple and mixed acid-base disorders were diagnosed using accepted rules. Results: Serum HCO 3 - was affected by age, normalized protein catabolic rate, interdialytic weight gain and length of interval between treatments. As expected, metabolic acidosis was the most common acid-base disorder, but respiratory acid-base disturbances, as simple or complex disorders, were found in 41% of the measurements. Respiratory alkalosis was seen more frequently than respiratory acidosis, but the latter disorder was more commonly associated with serious comorbidities. Conclusions: Respiratory acid-base disorders are an important component of the acid-base abnormalities seen in hemodialysis patients and are not identified by measuring total CO 2 concentration; hence, complete acid-base measurements are needed to determine the components of hemodialysis patients' acid-base status that are contributing to mortality risk.

Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders.

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.

Prevalence and predictors of intra-abdominal hypertension and compartment syndrome in surgical patients in critical care units at Kenyatta National Hospital.

BACKGROUND: Intra-abdominal hypertension (IAH) affects almost every organ sytem.If it is not detected early and corrected, mortality would be high. The prevalence of IAH and abdominal compartment syndrome (ACS) at Kenyatta National Hospital (KNH) critical care units is not known. The aim of this sudy was to determine the prevalence and factors associated with development of IAH/ACS among critically ill surgical patients. METHODS: This was a cross sectional descriptive study involving surgical patients in critical care units at KNH, carried out from March 2015 to October 2015. One hundred and thirteen critically ill and ventilated patients 13 years or older were recruited into the study. Krohn's intravesical method was used to measure intra- abdominal pressure (IAP). Measurements were done at first contact, then at 12 and 24 h. Additional parameters recorded included: laboratory tests such as serum bilirubin and total blood count as well as clinical parameters such as urine output, vital signs and peak airway pressure, among others. Frequency, means and standard deviation were used to describe the data. Categorical variables e.g. age, were analysed using Chi square test and continous variables using student 't' test and Mann Whitney test as appropriate RESULT: A total of 113 consecutive surgical patients admitted to the critical care units were recruited. Of our study population, 71.7% (by IAP max) and 67.3% (by IAP mean) had IAH. Abdominal compartment syndrome (ACS) developed in 4.4% of the population. The following factors were significant determinants of risk of IAH : amount of IV fluids over 24 h (3949.6 vs 2931.1, p = 0.003, adjusted OR 1.0 [1.0-1.002]), haemoglobin values at admission (9.9 vs 12.0, p = <0.012, adjusted OR 0.6 [0.4-0.9]), peak airway pressure (28.4 vs 17.3; p = 0.018, adjusted OR 1.6 [1.1-2.4]) and synchronised intermittent mandatory ventilation (SIMV) (60 vs 32; p = 0.041, adjusted OR 1.4 [0.78-2.04]). Of those who had IAH; age, amount of iv fluids over 24 h, fluid balance and ventilator mode were significant determinants of risk of progression to ACS . CONCLUSION: The prevalence of intraabdominal hypertension and abdominal compartment syndrome at KNH is high. Clinical parameters pertaining to fluids administration and ventilator mode are siginificant determinants.

Evaluation of acid-base status in patients admitted to ED-physicochemical vs traditional approaches.

BACKGROUND: The aim of this study is to evaluate the value of physicochemical, base excess (BE), and plasma bicarbonate concentration ([HCO3(-)]) approaches on the assessment of acid-base status in patients presented to the emergency department (ED). METHODS: Upon presentation at ED, patients whose arterial blood was deemed in need of analysis were studied. Arterial blood gases, serum electrolytes, and proteins were measured and used to derive [HCO3(-)], BE, anion gap (AG), AG adjusted for albumin (AGadj), strong ion difference, strong ion gap (SIG) and SIG corrected for water excess/deficit (SIGcor). In each patient the acid-base status was evaluated using the BE, [HCO3(-)], and physicochemical approaches. RESULTS: A total of 365 patients were studied. Compared with BE (n = 202) and [HCO3(-)] (n = 151), physicochemical approach (n = 279) identified significantly more patients with metabolic acid-base disturbances (P < .0001). Significantly fewer patients with unmeasured anions acidosis were identified with AGadj than with SIGcor (164 vs 230; P < .0001). On the basis of BE, 75 patients had normal acid-base balance, and 65 (87%) of them exhibited at least 1 hidden acid-base disturbance, identified by the physicochemical approach. The corresponding values with [HCO3(-)] approach were 108 and 95 (88%) patients. When patients with high AGadj were excluded, 44 patients with BE and 67 with [HCO3(-)] approach had normal acid-base status, and most of them exhibited at least 1 acid-base disturbance with the physicochemical approach, whereas 12 and 21 patients, respectively, had high SIGcor. CONCLUSION: Compared with the BE and [HCO3(-)] methods, the physicochemical approach has a better diagnostic accuracy to identify metabolic acid-base disturbances.

Use of different approaches of acid-base derangement to predict mortality in critically ill patients.

BACKGROUND: There have been controversial data regarding the application of acid-base analysis based on Stewart methodology to predict clinical outcome in different populations. OBJECTIVE: To compare predictive ability of the physicochemical approach and the traditional bicarbonate approach of acid-base analysis in critically ill patients in relation to 28-days mortality and to evaluate the use of the physico chemical approach determined by the strong ion gap (SIG) in 1) medical compared to surgical critically ill patients; and 2) sepsis compared to non-sepsis patients. MATERIAL AND METHOD: This retrospective cohort study included 410 critically ill patients in the adult medical and surgical intensive care units (ICU) at a tertiary care hospital over a 2-year period. For each patient, values derived from the bicarbonate approaches including anion gap (AG), corrected anion gap (cAG) and lactate and those obtained from the physicochemical approach like SIG were simultaneously computed at ICU admission. The comparison of predictive ability between different approaches was assessed by forward stepwise logistic regression and the area under the receiver operating characteristic (aROC) curves. RESULTS: Of the 410 patents enrolled, 205 (50%) were admitted in the medical ICU and 226 patients (55%) were male. Overall 28-day mortality was 44.6% (183/410). The comparison between medical and surgical patients showed no difference in age (59 vs. 64 yr), APACHE II score (21 vs. 20), presence of sepsis (71% vs. 70%) and 28-day mortality (45% vs. 44%). Acid-base disturbance in non-survivors (n = 183) and survivors (n = 227) determined by pH (7.39 +/- 0.04 vs. 7.41 +/- 0.01), serum bicarbonate (16.0 +/- 6.1 vs. 17.9 +/- 7.4) and PaCO2 (32.4 +/- 13.4 vs. 29.4 +/- 8.2) were comparable. However non-survivors had higher levels of SIG (9.7 +/- 6.2 vs. 6.4 +/- 5.2) and cAG (27.5 +/- 8.8 vs. 20.3 +/- 8.6) than survivors did. According to a ROC curves, the predictive ability to discriminate between survivors and non-survivors of lactate, cAG AG and SIG are 0.77, 0.72, 0.68 and 0.67, respectively. Correlations between the SIG and values derived from bicarbonate approach are fair. There was no difference in SIG values between surgical and medical patients with the same severity scores. Sepsis patients (n = 291) had significantly higher SIG than non-sepsis patients (n = 129) did (8.81 +/- 6.38 vs. 5.74 +/- 4.14; p = 0.01). CONCLUSION: Compared to the traditional approach, an alternative Stewart approach does not provide any greater advantage to predict mortality in the studied population. Because of complex calculation, the usefulness of such approach on the routine clinical practice may be limited.

Encephalopathies caused by electrolyte disorders.

Some of the most common reasons for metabolic neurologic disturbances in the setting of a general hospital are frequently encountered electrolyte and related osmolality disorders. Hyperosmolality is usually related to hypernatremia and/or hyperglycemia. Identifying the cause and carefully calculating the water deficit is crucial to appropriate management. Hyponatremia may be hypertonic, isotonic, or hypotonic. When hypotonic, it may be hypervolemic, euvolemic, or hypovolemic in nature. Determining the precise nature of the hyponatremia allows the clinician to focus the therapy appropriately. The rate of development of hyponatremia is crucial to safe and appropriate treatment. In acutely developing hyponatremia, hypertonic saline is required, whereas in slowly developing hyponatremia, water restriction and slow correction is required to avoid the syndrome of osmotic demyelination. Disorders of potassium metabolism are also common electrolyte disorders seen in the general hospital. Appropriate diagnosis and management of hyperkalemia and hypokalemia are also discussed.

Electrolyte imbalance in COVID-19 patients admitted to the Emergency Department: a case-control study.

In patients visiting the emergency department (ED), a potential association between electrolytes disturbance and coronavirus disease 2019 (COVID-19) has not been well studied. We aim to describe electrolyte disturbance and explore risk factors for COVID-19 infection in patients visiting the ED. We carried out a case-control study in three hospitals in France, including adult ED inpatients (≥ 18 years old). A total of 594 ED case patients in whom infection with COVID-19 was confirmed, were matched to 594 non-COVID-19 ED patients (controls) from the same period, according to sex and age. Hyponatremia was defined by a sodium of less than 135 mmol/L (reference range 135-145 mmol/L), hypokalemia by a potassium of less than 3.5 mmol/L (reference range 3.5-5.0 mmol/L), and hypochloremia by a chloride of less than 95 mmol/L (reference range 98-108 mmol/L). Among both case patients and controls, the median (IQR) age was 65 years (IQR 51-76), and 44% were women. Hyponatremia was more common among case patients than among controls, as was hypokalemia and hypochloremia. Based on the results of the multivariate logistic regression, hyponatremia, and hypokalemia were associated with COVID-19 among case patients overall, with an adjusted odds ratio of 1.89 [95% CI 1.24-2.89] for hyponatremia and 1.76 [95% CI 1.20-2.60] for hypokalemia. Hyponatremia and hypokalemia are independently associated with COVID-19 infection in adults visiting the ED, and could act as surrogate biomarkers for the emergency physician in suspected COVID-19 patients.

Early-Life Multiple Sevoflurane Exposures Alleviate Long-term Anxiety-Like Behaviors in Mice via the proBDNF/ERK Pathway.

Early-life multiple anesthetics exposure causes neurotoxicity and hence cognitive dysfunction on developing brain. However, the effects of early-life multiple sevoflurane exposures on emotional changes, especially upon stress, are far beyond understood. In young male C57BL6/J mice, the present study showed that 3% sevoflurane inhalation for 2 h in three consecutive days did not influence anxiety-like behaviors as measured by open field test, light dark transition, and elevated plus maze test. In addition, foot shocks stress induced both the short- and long-term anxiety-like behaviors. However, triple sevoflurane exposures ameliorated the long-term anxiety-like behaviors induced by the foot shocks. In parallel, foot shocks stress upregulated the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and brain-derived neurotrophic factor precursor (proBDNF) in the anterior cingulate cortex (ACC), which were significantly inhibited by triple sevoflurane exposures. Immunofluorescence further indicated that the increased p-ERK was mainly expressed in the proBDNF-positive staining cells. Intra-ACC injection of recombinant proBDNF protein upregulated the p-ERK expression and blocked the anxiolytic effect of sevoflurane exposure on long-term anxiety-like behaviors. Therefore, our study demonstrated that multiple sevoflurane exposures alleviate long-term anxiety-like behaviors upon acute stress in young mice by inhibiting proBDNF-ERK signaling in the ACC.

Dyselectrolytemias and arrhythmias.

Critical care patients are submitted to multiple derangements of vital parameters. Even in patients with a normally performing heart, its electrical activity can be strongly influenced by dyselectrolytemias, acid-base imbalance and aggressive drug therapy. In this paper, the basic principles of the electrophysiologic properties of the heart are reviewed, and the impact of dyselectrolytemias on heart excitability are underlined. Some clinically relevant aspects are described in greater depth, with respect to life-threatening arrhythmias.

Increased compensatory kidney workload results in cellular damage in a short time porcine model of mixed acidemia - Is acidemia a 'first hit' in acute kidney injury?

Acute kidney injury (AKI) corrupts the outcome of about 50% of all critically ill patients. We investigated the possible contribution of the pathology acidemia on the development of AKI. Pigs were exposed to acidemia, acidemia plus hypoxemia or a normal acid-base balance in an experimental setup, which included mechanical ventilation and renal replacement therapy to facilitate biotrauma caused by extracorporeal therapies. Interestingly, extensive histomorphological changes like a tubular loss of cell barriers occurred in the kidneys after just 5 hours exposure to acidemia. The additional exposure to hypoxemia aggravated these findings. These 'early' microscopic pathologies opposed intra vitam data of kidney function. They did not mirror cellular or systemic patterns of proinflammatory molecules (like TNF-α or IL 18) nor were they detectable by new, sensitive markers of AKI like Neutrophil gelatinase-associated lipocalin. Instead, the data suggest that the increased renal proton excretion during acidemia could be an 'early' first hit in the multifactorial pathogenesis of AKI.