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BACKGROUND To evaluate the event rate of major adverse kidney events within 30 days (MAKE30) in acute pancreatitis (AP) and its potential risk factors. METHODS A retrospective analysis of a tertiary center data on all AP patients admitted within 72 h after onset of abdominal pain between June 2015 and June 2019 was conducted. MAKE30 - a composite of death, new renal replacement therapy (RRT), or persistent renal dysfunction (PRD) - and its individual components were retrieved at discharge or 30 days. Logistic regression analysis was used to assess the risk factors for MAKE30. RESULTS 295 patients were enrolled and 16% experienced MAKE30. For individual components, the incidence was 3% for death, 15% for new RRT, and 5% for PRD. In multivariate logistic regression analysis, hyperchloremia at admission [OR = 8.38 (1.07-65.64); P = 0.043] and SOFA score [OR 1.63 (1.18-2.26); P = 0.003] were independent risk factors in predicting MAKE30. Further analysis showed that patients with hyperchloremia had more requirements of RRT (57% vs. 10%, P

Supplemental Digital Content is available in the text., Lithium, a mood stabilizer used in the treatment of bipolar disorder is known for its anti-inflammatory properties with the discussion of its potential use in COVID-19 infection. The SARS-CoV-2 virus causing COVID-19 infection is known to enter the target cells through angiotensin converting enzyme-2 receptors present in abundance in the lung and renal tissue. Recent research supports the evidence for direct renal injury by viral proteins. Here we report two patients with bipolar disorder presenting with lithium toxicity in the presence of COVID-19 infection. Two patients with bipolar disorder, maintaining remission on lithium prophylaxis, presented to the psychiatric emergency with recent-onset fever and altered sensorium. Both the patient’s investigations revealed lithium toxicity, elevated serum creatinine, urea and inflammatory markers. Hypernatremia, hyperkalaemia, and hyperchloremia were seen in one patient. Lithium and other psychotropic medications were stopped immediately, and COVID-19 treatment was initiated. Patient with clinical signs of lithium toxicity, hypernatremia, hyperkalaemia, and hyperchloremia developed ventricular tachycardia. He survived and regained consciousness after 2 weeks of aggressive conservative management. However, another patient died of acute respiratory failure on day 3. Possible direct infection of the kidney by SARS-CoV-2 viral proteins can manifest with acute kidney injury and lithium toxicity among patients on long-term lithium therapy. Health professionals treating COVID-19 infection among individuals on lithium therapy should be aware of the possibility of lithium toxicity in the background of renal injury.

Mortalitas sepsis dan syok sepsis hampir 20% per tahun dari semua kematian global. Sepsis dan syok sepsis merupakan penyebab 50% pasien dirawat di Intensive Care Unit (ICU). Kristaloid menjadi terapi cairan yang tepat menurut “The Surviving Sepsis Campaign Bundle: 2018 (SSC 2018)”. Kristaloid terbagi menjadi dua jenis, yaitu balanced dan unbalanced crystalloids. Perbedaan kandungan elektrolit keduanya dapat memengaruhi outcome pasien. Penelitian ini bertujuan mengetahui perbedaan pengaruh balanced dan unbalanced crystalloids pada sepsis dan syok sepsis dalam aspek mortalitas, kejadian hiperkloremia, dan lama tinggal di rumah sakit (RS). Metode yang digunakan adalah systematic review. Tempat penelitian berupa pencarian artikel penelitian pada online database dengan waktu penelitian, yaitu artikel dari tahun 2017 hingga 2021. Seleksi studi menggunakan PRISMA, kirteria restriksi dan PICO. Telaah artikel didapatkan 6 dari 249 artikel yang memenuhi syarat. Hasil analisis adalah mortalitas lebih rendah pada grup balanced crystalloids, kejadian hiperkloremia lebih tinggi pada unbalanced crystalloids, namun lama tinggal di RS di kedua grup tidak ada perbedaan signifikan. Simpulan penelitian adalah balanced crystalloids lebih efektif daripada unbalanced crystalloids dalam aspek menurunkan mortalitas dan kejadian hiperkloremia, namun tidak mengenai lama tinggal. Differences in the Effect of Balanced and Unbalanced Crystalloids as Fluid Therapy in Sepsis and Septic Shock: A Systematic Review Sepsis and septic shock contribute to almost 20% per year to the global total deaths. Sepsis and septic shock are also the the leading causes for patients to be treated in the Intensive Care Unit (ICU), with 50% of the patients treated in this unit due to sepsis and septic shock. Crystalloid is the appropriate thereapy for these conditions according to “The Surviving Sepsis Campaign Bundle: 2018 (SSC 2018)”. Crystalloids are divided into two types: balanced and unbalanced crystalloids. This study aimed to determine the difference between the effects of balanced and unbalanced crystalloids in sepsis and septic shock in terms of mortality, incidence of hyperchloremia, and length of stay in hospital. This was a systematic review on articles from the last five years using PRISMA, restriction criteria, and PICO. The review resulted in 6 out of 249 eligible articles. The results of the analysis demonstrated a lower mortality rate in the balanced crystalloids group while the incidence of hyperchloremia was higher in the unbalanced crystalloids group. No significant difference was found in the length of stay in hospital in both groups. Therefore, balanced crystalloids is more effective than unbalanced crystalloids in the aspect of reducing mortality and the incidence of hiperchloremia, with no significant difference in the length of stay in hospital.

Introduction: Hypernatremia can cause encephalopathy, rhabdomyolysis, and osmotic demyelination. Postpartum hypernatremia is an uncommon occurrence. The present study attempts to highlight clinical and radiological profile of three patients who had postpartum hypernatremia and to provide differential diagnosis of magnetic resonance imaging findings of postpartum hypernatremia. Aim:To study clinical and radiological profile of three patients who had postpartum hypernatremia and to provide differential diagnosis of magnetic resonance imaging findings of postpartum hypernatremia. Material and Methods:The present study was conducted in a tertiary care centre in South India between March 2014 to March 2018. Three patients had hypernatremia presenting in postpartum period. Demographic data, clinical details, results of laboratory examinations and neuroimaging details of these patients were recorded. Result:All three patients had hypernatremia presenting with encephalopathy. Spasticity was seen in all patients. Quadriparesis was seen in two patients. One patient had generalized tonic clonic seizures. Two patients had hypokalemia. All the three patients had Hyperchloremia, Azotemia and raised serum osmolality. Phosphorous levels was high in one patient. Creatine kinase levels was high in one patient. All patients had hypermagnesemia and normal calcium levels. Thrombocytopenia was seen in one patient. On neuroimaging, splenium of corpus callosum, hippocampus and posterior limb of internal capsule were involved in all patients. Cerebral peduncles in two patients. Corona Radiata and cerebellar white matter were involved in one patient. Conclusion:Early identification and meticulous management of hypernatremia is of paramount importance. Neuroimaging Findings in postpartum hypernatremia is distinct. Keywords: Postpartum, Hypernatremia, Encephalopathy, Osmotic demyelination, rhabdomyolysis.

Background This systematic review discusses a clinical physiology aspect of chloride in fluid therapy. Crystalloid solutions are one of the most widely used remedies. While generally used in medicine for almost 190 years, studies focused largely on their safety have only been published since the new millennium. The most widely used solution, normal saline, is most often referred to in this context. Its excessive administration results in hyperchloremic metabolic acidosis with other consequences, including higher mortality rates. Methods Original papers and review articles eligible for developing the present paper were identified by searching online in the electronic MEDLINE database. The keywords searched for included hyperchloremia, hypochloremia, and compound words containing the word “chloride,” infusion therapy, metabolic acidosis, renal failure, and review. Results A total of 21,758 papers published before 31 May 2020 were identified; of this number, 630 duplicates were removed from the list. Upon excluding articles based on their title or abstract, 1850 papers were screened, of which 63 full-text articles were assessed. Conclusions According to the latest medical concepts, dyschloremia (both hyperchloremia and hypochloremia) represents a factor indisputably having a negative effect on selected variables of clinical outcome. As infusion therapy can significantly impact chloride homeostasis of the body, the choice of infusion solutions should always take into account the potentially adverse impact of chloride content on chloremia and organ function.

BackgroundIncreased chloride in the context of intravenous fluid chloride load and serum chloride levels (hyperchloremia) have previously been associated with increased morbidity and mortality in select subpopulations of intensive care unit (ICU) patients (e.g patients with sepsis). Here, we study the general ICU population of the Medical Information Mart for Intensive Care III (MIMIC-III) database to corroborate these associations, and propose a supervised learning model for the prediction of hyperchloremia in ICU patients.MethodsWe assessed hyperchloremia and chloride load and their associations with several outcomes (ICU mortality, new acute kidney injury [AKI] by day 7, and multiple organ dysfunction syndrome [MODS] on day 7) using regression analysis. Four predictive supervised learning classifiers were trained to predict hyperchloremia using features representative of clinical records from the first 24h of adult ICU stays.ResultsHyperchloremia was shown to have an independent association with increased odds of ICU mortality, new AKI by day 7, and MODS on day 7. High chloride load was also associated with increased odds of ICU mortality. Our best performing supervised learning model predicted second-day hyperchloremia with an AUC of 0.76 and a number needed to alert (NNA) of 7—a clinically-actionable rate.ConclusionsOur results support the use of predictive models to aid clinicians in monitoring for and preventing hyperchloremia in high-risk patients and offers an opportunity to improve patient outcomes.

Our objective was to determine in children in the intensive care unit (ICU) the incidence of hyperchloremia (>110 mmol/L) and hypochloremia (

Objectives To investigate the acid‐base status of sick goats using the simplified strong ion difference (sSID) approach, to establish the quantitative contribution of sSID variables to changes in blood pH and HCO3 − and to determine whether clinical, acid‐base, and biochemical variables on admission are associated with the mortality of sick goats. Animals One hundred forty‐three sick goats. Methods Retrospective study. Calculated sSID variables included SID using 6 electrolytes unmeasured strong ions (USI) and the total nonvolatile buffer ion concentration in plasma (Atot). The relationship between measured blood pH and HCO3 −, and the sSID variables was examined using forward stepwise linear regression. Cox proportional hazard models were constructed to assess associations between potential predictor variables and mortality of goats during hospitalization. Results Hypocapnia, hypokalemia, hyperchloremia, hyperlactatemia, and hyperproteinemia were common abnormalities identified in sick goats. Respiratory alkalosis, strong ion acidosis, and Atot acidosis were acid‐base disorders frequently encountered in sick goats. In sick goats, the sSID variables explained 97% and 100% of the changes in blood pH and HCO3 −, respectively. The results indicated that changes in the respiratory rate (

Objective : Assessment of gas and electrolytic composition of venous blood in patients with chronic obstructive pulmonary disease (COPD) in relation to basic parameters of functional state of kidneys. Methods : 60 patients with COPD were divided into low and high exacerbation risk groups and were examined. Standard examinations were carried out; electrolytic and gas composition of venous blood and kidney functions were assessed. Results : Patients with high risk of COPD exacerbation demonstrated symptoms of respiratory failure, hyperchloremia, higher levels of potassium and albuminuria; there was a relationship between albuminuria and oximetric parameters. A significant dependence between glomerular filtration rate and COPD exacerbation rate was not detected, but there was its relationship with the smoking index, the result of the CAT questionnaire, Gensler index, instantaneous expiratory flow rate, lung capacity and peak expiratory flow rate were recorded. Conclusions : COPD is often characterized by combination of gas and electrolytic composition imbalance of venous blood and renal dysfunction. With a high risk of exacerbations, signs of respiratory failure, hyperchloremia, higher levels of potassium and albuminuria are more often observed. The relationship between daily albuminuria and oximetric parameters, glomerular filtration rate and partial blood oxygen tension, found in people at high risk of COPD exacerbation may indicate the need for correction of blood gas composition to prevent renal dysfunction.

BACKGROUND Electrolyte balance plays key role in maintaining homeostasis along with fluids in paediatric patients. The higher and lower value of critical electrolytes like sodium, potassium and chloride can affect cellular processes drastically as it may result in cardiac and neurological complications. This can alter patient status in terms of morbidity and mortality. Hence, Electrolyte imbalance significantly affects the quality of life of the patient. In this study we have analysed three electrolytes; sodium, potassium and chloride. The accurate measurement of electrolytes is an important prognostic indicator in PICU patients where greater attention and proper analysis is recommended. METHODS 180 paediatric patients in the age group of 2-15 years with various critical illnesses admitted in PICU of a tertiary care hospital were included in the study. The serum samples were analysed on Transasia Biomedicals XL 640 – a fully automated biochemistry analyser which has Ion Selective Electrode (ISE-Na/K/Cl) and diffraction grating for high resolution measurement. RESULTS Out of the 180 paediatric patients enrolled for the study, 83 were females and 97 were males. Hypernatremia was observed in 35% patients while hyponatremia in 31%. Hyperkalaemia was observed in 27% patients while hypokalaemia in 14%. Hyperchloremia in 24% while hypochloraemia 5% patients. CONCLUSIONS The electrolyte balance plays a key role in treatment of patients admitted in PICU. The accurate measurement of electrolyte like sodium, potassium & Chloride is an important prognostic indicator where greater attention and proper analysis is recommended. Also, the presence of electrolyte imbalance at the time of admission is an important prognostic indicator in critically ill children irrespective of primary disease process and needs to be addressed aggressively. The study helped us in maintaining the electrolyte ‘homeostasis’ in the body which is vital for the organ’s support and optimal function and also evaluating therapies and matching severity of illness in the PICU.

Hypernatremia has been associated with mortality in neurocritically ill patients, with and without traumatic brain injury (TBI). These studies, however, lack concomitant adjustment for hyperchloremia as a physiologically co-occurring finding despite the associations with hyperchloremia and worse outcomes after trauma, sepsis, and intracerebral hemorrhage. The objective of our study was to examine the association of concomitant hypernatremia and hyperchloremia with in-hospital mortality in moderate–severe TBI (msTBI) patients. We retrospectively analyzed prospectively collected data from the OPTIMISM-study and included all msTBI patients consecutively enrolled between 11/2009 and 1/2017. Time-weighted average (TWA) sodium and chloride values were calculated for all patients to examine the unadjusted mortality rates associated with the burden of hypernatremia and hyperchloremia over the entire duration of the intensive care unit stay. Multivariable logistic regression modeling predicting in-hospital mortality adjusted for validated confounders of msTBI mortality was applied to evaluate the concomitant effects of hypernatremia and hyperchloremia. Internal bootstrap validation was performed. Of the 458 patients included for analysis, 202 (44%) died during the index hospitalization. Fifty-five patients (12%) were excluded due to missing data. Unadjusted mortality rates were nearly linearly increasing for both TWA sodium and TWA chloride, and were highest for patients with a TWA sodium > 160 mmol/L (100% mortality) and TWA chloride > 125 mmol/L (94% mortality). When evaluated separately in the multivariable analysis, TWA sodium (per 10 mmol/L change: adjusted OR 4.0 [95% CI 2.1–7.5]) and TWA chloride (per 10 mmol/L change: adjusted OR 3.9 [95% CI 2.2–7.1]) independently predicted in-hospital mortality. When evaluated in combination, TWA chloride remained independently associated with in-hospital mortality (per 10 mmol/L change: adjusted OR 2.9 [95% CI 1.1–7.8]), while this association was no longer observed with TWA sodium values (per 10 mmol/L change: adjusted OR 1.5 [95% CI 0.51–4.4]). When concomitantly adjusting for the burden of hyperchloremia and hypernatremia, only hyperchloremia was independently associated with in-hospital mortality in our msTBI cohort. Pending validation, our findings may provide the rationale for future studies with targeted interventions to reduce hyperchloremia and improve outcomes in msTBI patients.

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of &gt, 108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster’s key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33–5.56) for cluster 1, and 4.83 (95% CI 3.21–7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53–5.70) for cluster 1 and 6.96 (95% CI 5.56–8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.

Introduction: Yellow oleander (Thevetia peruviana), which belongs to the Apocyanaceae family, is a common shrub seen throughout the tropics. All parts of the plant contain high concentrations of cardiac glycosides which are toxic to cardiac muscle and the autonomic nervous system. Here, we describe the clinical profile of patients with oleander poisoning and their outcomes. Methods and Materials: This retrospective study was conducted over a period of 12 months (March 2016 to February 2017). The data was extracted from the inpatient electronic medical records. Adult patients with a diagnosis of acute yellow oleander poisoning were included in the study. Descriptive statistics were obtained for all variables in the study and appropriate statistical tests were employed to ascertain their significance. Results: The study comprised 30 patients aged 30.77 ± 12.31 (mean ± SD) who presented at 12.29 ± 8.48 hours after consumption of yellow oleander. Vomiting (80%) was the most common presenting symptom. Metabolic abnormalities at presentation included hyperchloremia in 22 patients and metabolic acidosis (bicarbonate

Background: Previous studies have shown that chloride liberal fluids may be associated with worse renal outcomes. Deterioration of kidney function during hyperchloremia/chloride overload is believed to be induced by disturbances in renal perfusion, but exact mechanisms of chloride nephrotoxicity are unclear. The purpose of this randomized, crossover study was to investigate the effect of chloride loading on renal plasma flow (RPF), filtration fraction (FF) and glomerular filtration rate (GFR) in order to elucidate potential nephrotoxic mechanisms of chloride infusion. Methods: Fifteen healthy males were investigated twice after treatment with 2L isotonic saline and plasma-lyte with a wash-out period of at least 10 days. Within 15 mins after completion of infusion, the kidney parameters (RPF, FF and GFR) were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. Results: 99-mTc-DTPA renography showed reduction in both mean GFR (114 ± 13 ml/min vs.119 ± 12 ml/min, p = 0.04) and RPF (977 ± 272 ml/min vs. 1066 ± 197 ml/min, p = 0.19) and increasing FF (12% ± 2% vs. 11% ± 2%, p = 0.19) after 0.9% saline comparing to Plasmalyte, but only GFR reduction was statistically significant. Reduction in GFR and RPF and increasing in FF after 0.9% saline was observed in 10 subjects while in 5 others the reverse trend was shown. There were no statistically significant differences between mean systolic and diastolic blood pressure (BP) before and after each infusion except baseline diastolic BP. Weight changes (Δ weight) were similar after each infusion. Conclusions: We have demonstrated that high chloride infusion can affect kidney function in healthy subjects and seems to lead to impairment in both RPF and GFR.

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency in children. The capillary beta-hydroxybutyrate (BOHB) is increasingly used in the diagnosis and management of DKA. This study's objective is to assess the clinical and statistical correlation of BOHB with standard acidosis markers such as pH and HCO3. Materials and Methods: We retrospectively reviewed the electronic medical record of children aged 2 months to 16 years with DKA from January 2018 to January 2020 admitted in the pediatric intensive care unit of The Indus Hospital which is a tertiary care specialized center. All children received the treatment according to the standard protocol. Capillary blood BOHB was measured on admission, q 4–6 hourly, and blood glucose was also measured. All parameters were recorded on a structured sheet. Results: Among 1080 critically ill admissions, 26 patients (2.4%) were diagnosed as DKA. The mean age was 9.8 ± 3.8 years, and females were 54%. Half patients were newly diagnosed with Type 1-Insulin dependant diabetes mellitus (1DDM). Mild, moderate, and severe cases of DKA were 19%, 50%, and 31%, respectively. The median time to resolution of acidosis was 17 (10–39) h. At the time of resolution of acidosis, the correlation between capillary BOHB and blood pH (r = 0.11, P= 0.56), HCO3(r = 0.37, P = 0.86), AG (r = 0.37, P = 0.06), and base deficit (r = 0.04, P = 0.82) was noted. Hyperchloremia was present in 61.5% of cases. Five patients (19.2%) developed AKI that recovered. There was a strong clinical correlation of beta-hydroxybutyrate (BHOB) with standard acidosis markers of DKA management. Conclusion: Bedside capillary blood BOHB is a simple, inexpensive, point-of-care test that helps diagnose and treat DKA, especially in resource-limited settings, for avoiding unnecessary delays.

Background This study investigated the associations of fluctuations in serum chloride (Cl−) levels with 30-day mortality after intensive care unit (ICU) admission among critically ill patients. Methods We retrospectively analyzed the medical records of adult patients (≥18 years old) admitted to the ICU between January 2012 and December 2017. Positive and negative fluctuations in Cl− were defined as the differences between the Cl− upon ICU admission (baseline Cl−) and the maximum and minimum Cl− levels, respectively, measured within 72 h after ICU admission. Results The final analysis included 18,825 adult patients. In multivariable Cox regression analyses, the risk of 30-day mortality increased by 8% per 1-mmol L− 1 positive fluctuation in Cl− within 72 h (hazard ratio = 1.08, 95% confidence interval: 1.04–1.11, P 10%), normochloremia (97–110 mmol L− 1) or hyperchloremia (> 110 mmol L− 1) upon ICU admission. Furthermore, a negative fluctuation in the Cl− level during the first 72 h of an ICU stay was associated with a negative cumulative FB (

Background and Purpose— Global cerebral edema occurs in up to 57% of patients with subarachnoid hemorrhage (SAH) and is associated with prolonged hospital stay and poor outcome. Recently, admission brain edema was successfully graded using a simplified computed tomography-based semiquantitative score (subarachnoid hemorrhage early brain edema score [SEBES]). Longitudinal evaluation of the SEBES grade may discriminate patients with rapid and delayed edema resolution after SAH. Here, we aimed to describe the resolution of brain edema and to study the relationship between this radiographic biomarker and hospital course and outcome after SAH. Methods— For the current observational cohort study, computed tomography scans of 283 consecutive nontraumatic SAH patients admitted to the neurological intensive care unit of a tertiary hospital were graded based on the absence of visible sulci at 2 predefined brain tissue levels in each hemisphere (SEBES ranging from 0 to 4). A score of ≥3 was defined as high-grade SEBES. Multivariable regression models using generalized linear models were used to identify associated factors with delayed edema resolution based on the median time to resolution (SEBES ≤2) in SAH survivors. Results— Patients were 57 years old (interquartile range, 48–68) and presented with a median admission Hunt and Hess grade of 3 (interquartile range, 1–5). High-grade SEBES was common (106/283, 37%) and resolved within a median of 8 days (interquartile range, 4–15) in survivors (N=80). Factors associated with delayed edema resolution were early (150 mmol/L; adjusted odds ratio [adjOR], 4.88; 95% CI, 1.68–14.18), leukocytosis (>15 G/L; adjOR, 3.14; 95% CI, 1.24–8.77), hyperchloremia (>121 mmol/L; adjOR, 5.24; 95% CI, 1.64–16.76), and female sex (adjOR, 3.71; 95% CI, 1.01–13.64) after adjusting for admission Hunt and Hess grade and age. Delayed brain edema resolution was an independent predictor of worse functional 3-month outcome (adjOR, 2.52; 95% CI, 1.07–5.92). Conclusions— Our data suggest that repeated quantification of the SEBES can identify SAH patients with delayed edema resolution. Based on its’ prognostic value as radiographic biomarker, the SEBES may be integrated in future trials aiming to improve edema resolution after SAH.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary tubular dysfunction caused mainly by X-linked recessive inheritance ofAVPR2gene mutations. Pathogenic genes are a result of mutations inAVPR2on chromosome Xq28 and inAQP2on chromosome 12q13. The clinical manifestations of CNDI include polyuria, compensatory polydipsia, thirst, irritability, constipation, developmental delay, mental retardation, persistent decrease in the specific gravity of urine, dehydration, and electrolyte disorders (hypernatremia and hyperchloremia). Herein, we report a rare case of CNDI caused by anAVPR2mutation in a 2-year-old Chinese boy who had sustained polyuria, polydipsia, and irritability for more than 20 months. Laboratory examinations showed no obvious abnormality in blood sodium and chloride levels but decreased urine osmolality and specific gravity. Imaging findings were also normal. However, genetic analysis revealed a C > T transition leading to T273M missense mutations in AVPR2. We provided the boy a low-sodium diet and administered oral hydrochlorothiazide and indomethacin for 1 month, after which his clinical symptoms significantly improved. This case report suggests that CNDI is characterized by pathogenic T273M missense mutations alone and expands our understanding of the pathogenesis of CNDI.

Background: Hypertonic sodium chloride (HTS) is used in intensive care unit (ICU) settings to manage cerebral edema, intracranial hypertension, and for the treatment of severe hyponatremia. It has been associated with an increased incidence of hyperchloremia; however, there is limited literature focusing on hyperchloremic risk in neurologically injured patients. Objective: The primary objective of this study was to determine risk factors associated with development of hyperchloremia in a neurocritical care (NCC) ICU population. Methods: This was a retrospective case-control study performed in an adult NCC ICU and included patients receiving HTS. The primary outcome was to evaluate patient characteristics and treatments associated with hyperchloremia. Secondary outcomes included acute kidney injury and mortality. Results: Overall, 133 patients were identified; patients who were hyperchloremic were considered cases (n = 100) and patients without hyperchloremia were considered controls (n = 33). Characteristics and treatments were evaluated with univariate analysis and a logistic regression model. In the multivariate model, APACHE II Score, initial serum osmolality, total 3% saline volume, and total 23.4% saline volume were significant predictors for hyperchloremia. In addition, patients with a serum chloride greater than 113.5 mEq/L were found to have a higher risk of acute kidney injury (AKI) (adjusted OR 3.15; 95% CI 1.10-9.04). Conclusions: This study demonstrated APACHE II Score, initial serum osmolality, and total 3% and 23.4% saline volumes were associated with developing hyperchloremia in the NCC ICU. In addition, hyperchloremia is associated with an increased risk of AKI.

Background The superiority of either the traditional or Stewart based approach to acid-base balance has focused primarily on analyzing metabolic acidemia, with little attention given to patients with neutral pH. In this study, we evaluate metabolic disturbances in patients in the immediate postoperative period focusing on patients with neutral pH, while comparing the Stewart and traditional approach. Methods We conducted a single center retrospective observational cohort study. Over a 17-month period, data on arterial blood gas analysis, electrolytes, and albumin on the morning after surgery were retrieved from patients admitted to the postsurgical high dependency unit (HDU). Albumin-corrected anion gap (AG), apparent (SIDa) and effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated. Results Out of 1207 HDU admissions, 400 cases had a complete set of laboratory-data including albumin of which 281 presented with neutral pH (7.35 ≤ pH ≤ 7.45), 64 with acidemia (pH 7.45). In pH neutral patients, the following acidifying disturbances were found: SIDa was lowered in 101 (36%), and SIG was raised in 60 (21%). Base excess (BE) was decreased in 16 (6%) and corrected AG raised in 107 (38%). The alkalizing effect of hypoalbuminemia was present in 137 (49%). Out of 134 cases with normal BE and corrected AG, SIDa was lowered in 58 (43%). Out of 136 cases with normal SIDa and SIG, none had lowered BE and 28 increased AG (21%). Length of stay was significantly longer in patients with hypoalbuminemia, lowered SIDa, and increased corrected AG, but not decreased BE (hypoalbuminemia: 16 days vs. 10 days, P P = 0.015; increased AG: 16 days vs. 11 days, P P = 0.736). Conclusions Metabolic disturbances, characterized mainly by the presence of lowered SIDa, increased AG, and hypoalbuminemia, are frequent in our population with apparent neutral acid-base balance based on pH and base excess. These changes on the morning after surgery are associated with increased length of stay.

Background: In general, disease severity has been found to be associated with abnormal chloride levels in critically ill patients, but hyperchloremia is associated with mixed results regarding patient-centered clinical outcomes. We aimed to investigate the impact of maximum serum chloride concentration on the clinical outcomes of critically ill patients with large hemispheric infarction (LHI).Methods: We conducted a retrospective observational cohort study using prospective institutional neurocritical care registry data from 2013 to 2018. Patients with LHIs involving over two-thirds of middle cerebral artery territory, with or without infarction of other vascular territories, and a baseline National Institutes of Health Stroke Scale score of ≥13 were assessed. Those with a baseline creatinine clearance of Results: Of 90 patients, 20 (22.2%) died in-hospital. Patients who died in-hospital had significantly higher maximum serum chloride levels than did those who survived up to hospital discharge (139.7 ± 8.1 vs. 119.1 ± 10.4 mmol/L; p < 0.001). After adjusting for age, sex, and Glasgow coma scale score, each 5-mmol/L increase in maximum serum chloride concentration was independently associated with an increased risk of in-hospital mortality (adjusted odds ratio (aOR), 4.34; 95% confidence interval [CI], 1.98–9.50; p < 0.001). Maximum serum chloride level was also an independent risk factor for 3-month mortality (aOR, 1.99 [per 5 mmol/L increase]; 95% CI, 1.42–2.79; p < 0.001) and AKI occurrence (aOR, 1.57 [per 5 mmol/L increase]; 95% CI, 1.18–2.08; p = 0.002).Conclusions: High maximum serum chloride concentrations were associated with poor clinical outcomes in critically ill patients with LHI. This study highlights the importance of monitoring serum chloride levels and avoiding hyperchloremia in this patient population.

Objective There is recent interest in the association between hyperchloremic metabolic acidosis and adverse outcomes. In vitro, hyperchloremia causes renal vasoconstriction and fall in glomerular filtration rate (GFR). The objective of this retrospective, observational study is to examine associations between chloride level at admission to pediatric intensive care (PICU) and worst GFR and requirement for renal replacement therapy. Materials and Methods All admissions to PICU between 2009 and 2019 who received invasive mechanical ventilation and had blood gas analysis performed were included. Data analyzed included patient characteristics (age, gender, diagnosis, pediatric index of mortality [PIM]-2 score); results of initial blood gas; and maximum serum creatinine (then used to calculate minimum GFR). Primary outcome measure was worst GFR during PICU stay. Secondary outcome measures were requirement for renal replacement therapy and PICU mortality. Multivariable regression analysis was used to assess if admission chloride level was independently predictive of minimum GFR during PICU stay and to examine associations between hyperchloremia (>110 mEq/L) at admission and requirement for renal replacement therapy after adjustment for confounders. Results Data were available for 2,217 patients. Median age was 16.4 months and 39% of patients were hyperchloremic at admission to PICU. Admission chloride level was independently predictive of worst GFR during PICU stay after adjustment for known confounders. Patients with hyperchloremia were not more likely to require renal replacement therapy or die than patients with normochloremia. Conclusion Prospective studies are necessary to determine if high chloride, specifically chloride containing resuscitation fluids, have a causal relationship with poor outcomes.

Purpose We sought to describe the association between serum chloride levels and mortality among unselected cardiac intensive care unit (CICU) patients. Materials and methods We retrospectively reviewed adult patients admitted to our CICU from 2007 to 2015. The association of dyschloremia and hospital mortality was assessed in a multiple variable model including additional confounders, and the association of dyschloremia and post-discharge mortality were assessed using Cox proportional-hazards analysis. Results 9,426 patients with a mean age of 67±15 years (37% females) were included. Admission hypochloremia was present in 1,384 (15%) patients, and hyperchloremia was present in 1,606 (17%) patients. There was a U-shaped relationship between admission chloride and unadjusted hospital mortality, with increased hospital mortality among patients with hypochloremia (unadjusted OR 3.0, 95% CI 2.5–3.6, p Conclusion Abnormal serum chloride on admission to the CICU is associated with increased short- and long-term mortality, with hypochloremia being a strong independent predictor.

Diabetic ketoacidosis (DKA) is characterized by hyperglycemia, ketogenesis, and increased anion gap metabolic acidosis. Such derangements are accompanied by volume depletion as well as electrolyte disturbances. Resuscitation using traditional saline in DKA patients can exacerbate electrolyte abnormalities, in particular the production of hyperchloremia. Severe hypovolemia can result in acute kidney injury (AKI). The link between hyperchloremia and AKI is controversial. This study aimed to assess the relationship between hyperchloremia and AKI in pediatric patients with DKA and its impacts on clinical outcomes. This cross-sectional study was conducted on 70 children with DKA admitted to the pediatric intensive care unit in which all patients were subjected to detailed medical history taking and full clinical examination. Daily assessment of Na, K, urea, creatinine, chloride, arterial blood gases, and albumin/creatinine ratio (ACR) was done. AKI was defined as pRIFLE stage I and F. Hyperchloremia was detected in 65.7% of patients at admission and in 52.9% after 24 h (p = 0.17). AKI was documented in 28% of patients. At admission hyperchloremia was detected in 56% of patients without AKI versus 90% of patients with AKI (p = 0.007). After 24 h, hyperchloremia was detected in 48.4% patients without versus 100% of patients with AKI. Chloride was significantly positively correlated to duration of admission, creatinine, ACR, and negatively correlated to eGFR. The development of AKI in patients with DKA was accompanied by hyperchloremia, increased time to DKA resolution, and longer hospital stay. “A higher resolution version of the Graphical abstract is available as Supplementary information.”

BackgroundHyperchloremia and chloride load have been associated with worse clinical outcomes in critically ill patients. We sought to evaluate the electrolyte profile and clinical outcomes associated with a unit-wide transition from saline to balanced fluids for resuscitation and maintenance fluids in a pediatric intensive care unit (PICU).MethodsA before and after analysis of all patients admitted to the PICU in a large, urban, academic hospital between August 2018 and March 2020. The transition from the use of saline to the use of balanced fluids for both resuscitation and maintenance fluid as standard care occurred in June 2019. The primary outcome was day 3 acute kidney injury (AKI). The secondary outcomes included mortality, ventilator-free days (VFDs), need for renal replacement therapy (RRT), hospital length of stay (LOS), and electrolyte abnormalities.ResultsOverall, 2863 patients (47% female) with a day 3 AKI rate of 12.9% (n = 130) and a mortality rate of 2.8% (n = 79) were included. After adjusting for confounders (age, PRISM III, mechanical ventilation, and immunocompromised state, septic shock), there were no significant differences in the odds of day 3 AKI (pre 13%, post 12.5%; adjusted odds ratio [aOR] 0.96, 95%CI 0.65–1.42). There were no differences in the secondary outcomes. The post-intervention period had fewer patients with hyperchloremia (pre 15.5% vs. post 10.4%,p = p = 0.02) and more patients with hypochloremia (pre 9.5% vs. post 14.4%,p = p = ConclusionsFollowing a unit-wide implementation of balanced fluids as standard care, there were no differences in rates of day 3 AKI or other clinical outcomes. However, there were lower rates of hyperkalemia and hyperchloremia and higher rates of hypokalemia and hypochloremia. Further evaluation of the effect of balanced fluids and the clinical significance of electrolyte abnormalities in critically ill children is needed.

Background Hyperchloremia is associated with the risks of several morbidities and mortality. However, its relationship with acute kidney injury (AKI) and end-stage renal disease (ESRD) in patients undergoing coronary artery bypass grafting (CABG) remains unresolved. Methods A total of 2977 patients undergoing CABG between 2003 and 2015 were retrospectively reviewed from two tertiary hospitals. Patients were categorized by serum chloride levels into normochloremia (95–105 mmol/L), mild hyperchloremia (106–110 mmol/L), and severe hyperchloremia (> 110 mmol/L). The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD were calculated after adjustment for multiple covariates. The death-adjusted risk of ESRD was additionally evaluated. Results Postoperative AKI occurred in 798 patients (26.5%). The hyperchloremia group had a higher risk of AKI than the normochloremia group, wherein the risk was incremental depending on the severity of hyperchloremia, as follows: ORs were 1.26 (1.06–1.51) and 1.95 (1.52–2.51) in the mild and severe hyperchloremia groups, respectively. During a median period of 7 years (maximum 15 years), 70 patients (2.3%) had ESRD. The severe hyperchloremia group was at an elevated risk of ESRD compared with the normochloremia group, with an HR of 2.43 (1.28–4.63). Even after adjusting for the competing risk of death, hyperchloremia was associated with the risk of ESRD. Conclusions Preoperative hyperchloremia is associated with poor renal outcomes such as AKI and ESRD after CABG. Accordingly, serum chloride should be monitored in patients undergoing CABG.

Case summary A 9-month-old intact female domestic mediumhair cat presented with a 5-month history of obtundation, lethargy, hypernatremia (181 mmol/l; reference interval [RI] 151–158 mmol/l), hyperchloremia (142 mmol/l; RI 117–126 mmol/l), azotemia (blood urea nitrogen 51 mg/dl; RI 18–33 mg/dl), creatinine 3.0 mg/dl (RI 1.1–2.2 mg/dl), hyperphosphatemia (8.3 mg/dl; RI 3.2–6.3 mg/dl) and total hypercalcemia (11.4 mg/dl; RI 9–10.9 mg/dl), with concurrent polyuria with adipsia. Neurologic evaluation revealed proprioceptive deficits, and this finding paired with a history of focal seizure-like activity despite improving sodium concentrations suggested a cerebrothalamic lesion. For this reason, and historical and biochemical findings consistent with adipsic diabetes insipidus (DI), MRI of the brain was performed, which revealed a lesion of the hypophyseal fossa consistent with a pituitary cyst. Given the patient’s age and the timeline of clinical signs, a congenital pituitary cyst was strongly suspected. The patient was managed initially with intravenous fluids to correct the hypernatremia, then managed for more than 4 years with topical ocular desmopressin acetate administration and free water administered through a feeding tube. This cat’s clinical diagnosis included a congenital pituitary cyst with subsequent central DI and primary adipsia. Relevance and novel information The clinical presentations of primary adipsia or central DI are both rare in cats. This is the first report to describe these conditions occurring in a cat owing to a congenital pituitary cyst and describes successful long-term management of this condition.

Background We report a case of pseudo-hyperchloremia in a patient hospitalized in the dermatology department at the Mohammed V Military Hospital of Instruction in Rabat. The examination revealed self-medication with calcium bromo-galactogluconate, allowing the suspicion of an analytical interference on chloremia by bromides. Methods The determination of chloremia was done by indirect potentiometry on an Architect ci8200®. Results A biological assessment was carried out on admission, showed isolated hyperchloremia at 137 mmol/L (95 - 110 mmol/L), while the other electrolytes, the anion gap, and kidney function were normal. A follow-up electrolytes test one week after stopping calcium bromo-galactogluconate showed normalization of chloremia to 109 mmol/L. Conclusions The analytical interference of bromides on the chloride assay causes pseudo-hyperchloremia, an analytical anomaly not very well-known by clinicians.

Background: Acute diarrhea and severe dehydration (ADSD) is a common cause of under-5 mortality in low- and middle-income countries. There is a paucity of data on clinical profile of ADSD children presenting with severe non-anion gap metabolic acidemia (sNAGMA). Study was planned to delineate clinical profile, critical care needs, and outcome of these children. Methods: For this retrospective chart review, children (1mo-12yr) with ADSD and sNAGMA (pH

To determine the significance and impact of additional chloride testing as part of a diagnostic laboratory test battery for borderline primary hyperparathyroidism (pHPT).Retrospective database review of parathyroidectomy patients.A tertiary care, academic health sciences center.Patients referred to a head and neck endocrine clinic for evaluation and treatment for pHPT.After exclusions, there were a total of 226 patients who underwent parathyroidectomy for primary hyperparathyroidism with the requisite preoperative and postoperative labs. Seventy-seven additional patients who had a thyroid operation for a nonmalignant cause were included as controls. Of the 303 total patients, 166 had normal calcium levels (10.4 mg/dL), and 54 (32.5%) also exhibited hyperchloremia (106 mmol/L). Of the 47 patients with normal calcium and parathyroid hormone (PTH) levels (88 pg/mL), 6 (12.8%) had hyperchloremia, and of the 118 patients with normocalcemic pHPT, 48 (40.7%) were hyperchloremic. The area under the curve for the Cl:PO4 was 0.712. When using a cutoff of 33, the reported sensitivity and specificity of the curve were 58.4% and 28.6%, respectively.The Cl:PO4 ratio was a moderately sensitive test for the diagnosis of the borderline variants of primary hyperparathyroidism. The Ca:PO4 ratio was superior to the Cl:PO4 ratio. Our data also showed the superiority of preoperative calcium and ionized calcium over PTH when predicting the presence of pHPT.

Background: We aimed to describe the incidence of hospital-acquired dyschloremia and its association with in-hospital mortality in general hospitalized patients. Methods: All hospitalized patients from 2009 to 2013 who had normal admission serum chloride and at least two serum chloride measurements in the hospital were studied. The normal range of serum chloride was defined as 100&ndash, 108 mmol/L. Hospital serum chloride levels were grouped based on the occurrence of hospital-acquired hypochloremia and hyperchloremia. The association of hospital-acquired hypochloremia and hyperchloremia with in-hospital mortality was analyzed using logistic regression. Results: Among the total of 39,298 hospitalized patients, 59% had persistently normal hospital serum chloride levels, 21% had hospital-acquired hypochloremia only, 15% had hospital-acquired hyperchloremia only, and 5% had both hypochloremia and hyperchloremia. Compared with patients with persistently normal hospital serum chloride levels, hospital-acquired hyperchloremia only (odds ratio or OR 2.84, p &lt, 0.001) and both hospital-acquired hypochloremia and hyperchloremia (OR 1.72, p = 0.004) were associated with increased in-hospital mortality, whereas hospital-acquired hypochloremia only was not (OR 0.91, p = 0.54). Conclusions: Approximately 40% of hospitalized patients developed serum chloride derangements. Hospital-acquired hyperchloremia, but not hypochloremia, was associated with increased in-hospital mortality.

Objectives With the exception of 0.9% saline, little is known about factors that may contribute to increased serum chloride concentration (SCl−) in patients undergoing cardiac surgery. For the present study, the authors sought to characterize the association between administered chloride load from intravenous fluid and other perioperative variables, with peak perioperative SCl−. Design Secondary analysis of data from a previously published controlled clinical trial in which patients were assigned to a chloride-rich or chloride-limited perioperative fluid strategy (NCT02020538). Setting Academic medical center. Participants The study comprised 1,056 adult patients with normal preoperative SCl− undergoing cardiac surgery. Interventions None Measurements and Main Results Peak perioperative SCl− and hyperchloremia, defined as peak SCl− >110 mmol/L, were selected as co-primary endpoints. Regression modeling identified factors independently associated with these endpoints. Mean (standard deviation) peak perioperative SCl− was 114 (5) mmol/L, and hyperchloremia occurred in 824 (78.0%) of the cohort. In addition to administered volume of 0.9% saline, multivariate linear and logistic regression modeling consistently associated preoperative SCl− (regression coefficient 0.5; 95% confidence interval [CI] 0.4-0.6 mmol/L; odds ratio 1.60; 95% CI 1.41-1.82 per 1 mmol/L increase) and cardiopulmonary bypass duration (regression coefficient 0.1; 95% CI 0.1-0.2 mmol/L; odds ratio 1.12; 95% CI 1.06-1.19 per 10 minutes) with both co-primary outcomes. Multivariate modeling only explained approximately 50% of variability in peak SCl−. Conclusions The present study's data identified an association for both 0.9% saline administration and other nonfluid variables with peak perioperative SCl− and hyperchloremia. Stand-alone strategies to limit administration of chloride-rich intravenous fluid may have limited ability to prevent hyperchloremia in this setting.

Background Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation. Methods A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl− ≥ 109 mmol/L) and required hyperosmolar treatment. Results We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl− load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na+ concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, (p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups. Conclusions Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl− load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results. Trial registration clinicaltrials.gov # NCT03204955, registered on 6/28/2017

This study aimed to assess the one-year mortality risk based on discharge serum chloride among the hospital survivors. We analyzed a cohort of adult hospital survivors at a tertiary referral hospital from 2011 through 2013. We categorized discharge serum chloride, &le, 96, 97&ndash, 99, 100&ndash, 102, 103&ndash, 105, 106&ndash, 108, and &ge, 109 mmoL/L. We performed Cox proportional hazard analysis to assess the association of discharge serum chloride with one-year mortality after hospital discharge, using discharge serum chloride of 103&ndash, 105 mmoL/L as the reference group. Of 56,907 eligible patients, 9%, 14%, 26%, 28%, 16%, and 7% of patients had discharge serum chloride of &le, 109 mmoL/L, respectively. We observed a U-shaped association of discharge serum chloride with one-year mortality, with nadir mortality associated with discharge serum chloride of 103&ndash, 105 mmoL/L. When adjusting for potential confounders, including discharge serum sodium, discharge serum bicarbonate, and admission serum chloride, one-year mortality was significantly higher in both discharge serum chloride &le, 99 hazard ratio (HR): 1.45 and 1.94 for discharge serum chloride of 97&ndash, 99 and &le, 96 mmoL/L, respectively, p &lt, 0.001) and &ge, 109 mmoL/L (HR: 1.41, 0.001), compared with discharge serum chloride of 103&ndash, 105 mmoL/L. The mortality risk did not differ when discharge serum chloride ranged from 100 to 108 mmoL/L. Of note, there was a significant interaction between admission and discharge serum chloride on one-year mortality. Serum chloride at hospital discharge in the optimal range of 100&ndash, 108 mmoL/L predicted the favorable survival outcome. Both hypochloremia and hyperchloremia at discharge were associated with increased risk of one-year mortality, independent of admission serum chloride, discharge serum sodium, and serum bicarbonate.

Isotonic 0.9% sodium chloride (normal saline; NS) solution use is common, but its high chloride content has been shown to contribute to acid-base disturbances and acute kidney injury (AKI). As kidney transplant recipients are at high risk of postoperative AKI and renal replacement therapy, we aimed to evaluate the impact of perioperative NS administration on graft function after kidney transplantation. All adult patients undergoing deceased-donor kidney transplantation between January 2010 and December 2014 at the Rennes University Hospital were included. Logistic regression models were constructed to evaluate the association of hyperchloremia and hyperchloremic acidosis on delayed graft function (DGF), defined as the need for renal replacement therapy within the first week after transplantation. Three hundred and fifty-nine patients were included, 20% developed DGF. The mean (standard deviation) volume of NS infused in the operating room and in the standard postoperative intensive care unit stay was 4,832 (2,242) mL. In the first 24 postoperative hours, 11% of patients developed hyperchloremia and 11% developed hyperchloremic acidosis. These outcomes were not associated with significantly higher total volumes of NS administration or with DGF. In contrast, multivariable analysis showed that cold ischemia time, donor terminal creatinine, and perioperative NS volume were all independent predictors of DGF. Perioperative NS infusion volume was associated with DGF in deceased-donor kidney transplant recipients. Conversely, postoperative hyperchloremia and hyperchloremic acidosis were not associated with an increased risk of DGF, suggesting other mechanisms than a chloride effect.

Background and Purpose: While an association between hyperchloremia and worse outcomes, such as acute kidney injury and increased mortality, has been demonstrated in hemorrhagic stroke, it is unclear whether the same relationship exists after acute ischemic stroke. This study aims to determine the relationship between moderate hyperchloremia (serum chloride ≥115 mmol/L) and acute kidney injury in patients with ischemic stroke. Methods: This is a multicenter, retrospective, propensity-matched cohort study of adults admitted for acute ischemic stroke. The primary objective was to determine the relationship between moderate hyperchloremia and acute kidney injury, as defined by the Acute Kidney Injury Network criteria. Secondary objectives included mortality and hospital length of stay. Results: A total of 407 patients were included in the unmatched cohort (332 nonhyperchloremia and 75 hyperchloremia) and 114 patients (57 in each group) were matched based upon propensity scores. In the matched cohort, hyperchloremia was associated with an increased risk of acute kidney injury (relative risk 1.91 [95% confidence interval 1.01-3.59]) and a longer hospital length of stay (16 vs 12 days; P = .03). Mortality was higher in the hyperchloremia group (19.3% vs 10.5%, P = .19), but this did not reach statistical significance. Conclusions: In this study, hyperchloremia after ischemic stroke was associated with increased rates of acute kidney injury and longer hospital length of stay. Further research is needed to determine which interventions may increase chloride levels in patients with acute ischemic stroke and the association between hyperchloremia and clinical outcomes.

Toru Watanabe Department of Pediatrics, Niigata City General Hospital, Niigata City 950-1197, Japan Abstract: Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal acidification due to a failure of type A intercalated cells (A-ICs) in the collecting tubule. dRTA is characterized by persistent hyperchloremia, a normal plasma anion gap, and the inability to maximally lower urinary pH in the presence of systemic metabolic acidosis. Common clinical features of dRTA include vomiting, failure to thrive, polyuria, hypercalciuria, hypocitraturia, nephrocalcinosis, nephrolithiasis, growth delay, and rickets. Mutations in genes encoding three distinct transport proteins in A-ICs have been identified as causes of dRTA, including the B1/ATP6V1B1 and a4/ATP6V0A4 subunits of the vacuolar-type H+-ATPase (H+-ATPase) and the chloride–bicarbonate exchanger AE1/SLC4A1. Homozygous or compound heterozygous mutations in ATP6V1B1 and ATP6V0A4 lead to autosomal recessive (AR) dRTA. dRTA caused by SLC4A1 mutations can occur with either autosomal dominant or AR transmission. Red blood cell abnormalities have been associated with AR dRTA due to SLC4A1 mutations, including hereditary spherocytosis, Southeast Asia ovalocytosis, and others. Some patients with dRTA exhibit atypical clinical features, including transient and reversible proximal tubular dysfunction and hyperammonemia. Incomplete dRTA presents with inadequate urinary acidification, but without spontaneous metabolic acidosis and recurrent urinary stones. Heterozygous mutations in the AE1 or H+-ATPase genes have recently been reported in patients with incomplete dRTA. Early and sufficient doses of alkali treatment are needed for patients with dRTA. Normalized serum bicarbonate, urinary calcium excretion, urinary low-molecular-weight protein levels, and growth rate are good markers of adherence to and/or efficacy of treatment. The prognosis of dRTA is generally good in patients with appropriate treatment. However, recent studies showed an increased frequency of chronic kidney disease (CKD) in patients with dRTA during long-term follow-up. The precise pathogenic mechanisms of CKD in patients with dRTA are unknown. Keywords: urinary acidification, clinical features, treatment, prognosis, gene, pathogenesis

Introduction: Administrating intravenous fluids is one of the most frequent practices in the care of critically ill patients, since most of them present shock or hypotension from any cause. The rapid and aggressive administration of these fluids may lead to adverse results, including acute renal failure and hydroelectrolytic disorders which are highly associated with fatal outcomes. Objectives: To establish the association between hyperchloremia and mortality in patients admitted to the intensive care unit (ICU) of Hospital Universitario de San Jose between August 2013 and January 2017, in addition to their demographic characteristics, the incidence of chloride abnormalities, and its association to renal failure. Methods: Analytic retrospective cohort study in the adult ICU at the Hospital Universitario de San Jose from August 1, 2013 to January 31, 2017. Results: A total of 839 patients were evaluated, 210 exposed and 629 not exposed. The relative risk of death for those who developed hyperchloremia was 3.12 (95% confidence interval [CI] 2.16^.49) (P

Hyperchloremic metabolic acidosis, particularly renal tubular acidosis, can pose diagnostic challenges. The laboratory phenotype of a low total carbon dioxide content, normal anion gap, and hyperchloremia may be misconstrued as hypobicarbonatemia from renal tubular acidosis. Several disorders can mimic renal tubular acidosis, and these must be appropriately diagnosed to prevent inadvertent and inappropriate application of alkali therapy. Key physiologic principles and limitations in the assessment of renal acid handling that can pose diagnostic challenges are enumerated.

Purpose The aim of this study was to determine whether serum chloride and changes in serum chloride over time were associated with acute kidney injury (AKI) or intensive care unit (ICU) mortality in a heterogenous critically ill population. Materials and methods The study was a retrospective observational study of 250 adult patients admitted to a multidisciplinary academic ICU. Serum chloride within 48 h of admission, changes in chloride, and other biochemical and clinical parameters were evaluated as predictors of AKI and mortality. Results Hyperchloraemia occurred in 143 (57.2%) patients within 48 h of ICU admission. Hyperchloraemia at 48 h was significantly associated with AKI, OR = 6.44 (95% CI 2.95–14.10) and mortality, OR = 2.46 (95% CI 1.22–4.94) on univariate analysis, with this association persisting on multivariable analysis. An increase in serum chloride was also associated with a significantly increased risk of AKI and mortality on univariate analysis. Hyperchloraemia on admission was, however, not associated with AKI or death. Of the 150 patients with AKI, 147 (98.0%) had developed AKI by 48 h. Conclusions Hyperchloraemia and increasing serum chloride are associated with adverse outcomes in critically ill patients. There is equipoise as to whether this represents an association, an epiphenomenon or causation.

OBJECTIVE This study examines temporal trends in treatment-related outcomes surrounding a diabetic ketoacidosis (DKA) performance improvement intervention consisting of mandated intensive care unit admission and implementation of a standardized management pathway, and identifies physical and biochemical characteristics associated with outcomes in this population. METHODS A retrospective cohort of 1225 children with DKA were identified in the electronic health record by international classification of diseases codes and a minimum pH less than 7.3 during hospitalization at a quaternary children's hospital between April, 2009 and May, 2016. Multivariable regression examined predictors and trends of hypoglycemia, central venous line placement, severe hyperchloremia, head computed tomography (CT) utilization, treated cerebral edema and hospital length of stay (LOS). RESULTS The incidence of severe hyperchloremia and head CT utilization decreased during the study period. Among patients with severe DKA (presenting pH

Chloride is the principal anion of the extracellular fluid and vital for both serum electroneutrality and acid-base homeostasis. The aim of this review is to investigate the relevance of dyschloremia in the critically ill. An extensive literature research was conducted on www.pubmed.org . In addition, the references of included articles were searched for further possible investigation regarding chloride. Articles investigating the relevance of dyschloremia in the critically ill were included. All articles were screened in regard to dyschloremia in the critically ill. Chloride is essential for blood pressure control, decarboxylation/gas transport, renal function, and gastrointestinal homeostasis. “Dyschloremia,” i.e., serum chloride levels not within the limits of normal, may commonly be observed on ICUs and appear mainly induced by iatrogenic measures (i.e., infusion of chloride-rich fluids). Hypo- and hyperchloremia appear linked to increased mortality in defined ICU populations, but evidence is sparse. Data show that hyperchloremia may not only be linked to hyperchloremic metabolic acidosis, but also to increased hemodynamic instability and vasopressor need (e.g., in patients after major surgery). Nevertheless, it is currently unknown whether such effects would be directly or indirectly mediated. Moreover, recent evidence points to an increased incidence of acute kidney injury and need for renal replacement therapy in patients with advanced hyperchloremia. Current knowledge on chloride is largely limited by heterogeneous trial design and mostly abundant data on specific fluid replacement strategies. The aim of this review is to summarize key consequences of chloride in critical illness and to discuss implications for daily clinical practice and future research.

Metabolic acidosis is the most frequent acid-base disorder in patients of the Intensive Care Unit. By conventional approach based onpH value, [HCO3–], and base deficit (BD) from blood gas analyzer (BGA) measurement are often inappropriate with the clinical stateand inadequate in explaining the mechanism of the metabolic acidosis. The Stewart approach states that the blood pH is determinedby a strong ion difference (SID), the carbon dioxide tension (pCO2), the total concentration of non-volatile weak acid. The Stewartapproach may give a better understanding of the mechanisms that underlie the metabolic acidosis. The purpose of this study is to knowthe correlation of blood pH value measurement from BGA and calculation based on Stewart approach and identifying the mechanismsthat underlie a metabolic acidosis. In this study an analytic observational cross-sectional method was used. The examined subjectsconsisted of 71 patients who were admitted with a metabolic acidosis at the ICU from July up to August 2007. All patients were measuredfor their blood pH, pCO2, [HCO3–], BD, sodium, potassium, calcium, magnesium, chloride, lactate, albumin, and phosphate. The resultwas reported as the mean and standard deviation. The data were analyzed by Pearson's correlation test and linier multiple regression.Statistical significance was determined at p < 0.05. The mean values of blood pH measurement from BGA and blood pH calculationbased on the Stewart approach were 7.33 (0.11) and 7.49 (0.11) (r = 0.681; p < 0.001). Most patients had two underlying mechanisms ofmetabolic acidosis. Hyperlactatemia was present in 61.8%, hyperchloremia was present in 58.2% of patients. Based on this study so far,by using the Stewart approach there is an excellent and significant correlation between the blood pH measurement from BGA and bloodpH calculation. Hyperlactatemia and hyperchloremia are the main causes of the metabolic acidosis in patients of the ICU ward.

The optimal fluid management in critically ill children is currently under investigation with several studies suggesting that hyperchloremia, chloride load, and the use of chloride-rich fluids contribute to worse outcomes. This is a single-center retrospective cohort study of Pediatric Intensive Care Unit patients from 2008 to 2016 requiring continuous renal replacement therapy (CRRT). Patients were excluded if they had end-stage renal disease, a disorder of chloride transport, or concurrent provision of extracorporeal membrane oxygenation therapy. Patients (n = 66) were dichotomized into two groups (peak chloride (Cl) ≥ 110 mmol/L vs. peak Cl

Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if a similar association exists among critically ill children. We determined if hyperchloremia is associated with poor outcomes in children with septic shock.Retrospective analysis of a pediatric septic shock database.Twenty-nine PICUs in the United States.Eight hundred ninety children 10 years and younger with septic shock.None.We considered the minimum, maximum, and mean chloride values during the initial 7 days of septic shock for each study subject as separate hyperchloremia variables. Within each category, we considered hyperchloremia as a dichotomous variable defined as a serum concentration greater than or equal to 110 mmol/L. We used multivariable logistic regression to determine the association between the hyperchloremia variables and outcome, adjusted for illness severity. We considered all cause 28-day mortality and complicated course as the primary outcome variables. Complicated course was defined as mortality by 28 days or persistence of greater than or equal to two organ failures at day 7 of septic shock. Secondarily, we conducted a stratified analysis using a biomarker-based mortality risk stratification tool. There were 226 patients (25%) with a complicated course and 93 mortalities (10%). Seventy patients had a minimum chloride greater than or equal to 110 mmol/L, 179 had a mean chloride greater than or equal to 110 mmol/L, and 514 had a maximum chloride greater than or equal to 110 mmol/L. A minimum chloride greater than or equal to 110 mmol/L was associated with increased odds of complicated course (odds ratio, 1.9; 95% CI, 1.1-3.2; p = 0.023) and mortality (odds ratio, 3.7; 95% CI, 2.0-6.8; p0.001). A mean chloride greater than or equal to 110 mmol/L was also associated with increased odds of mortality (odds ratio, 2.1; 95% CI, 1.3-3.5; p = 0.002). The secondary analysis yielded similar results.Hyperchloremia is independently associated with poor outcomes among children with septic shock.

Hyperchloremia leads to adverse effects like increase in pro-inflammatory mediators, anaemia and renal dysfunction. Aim of this study is to determine the association of hyperchloremia with rise in C-reactive protein (CRP), serum ferritin, lactate dehydrogenase (LDH), serum creatinine and anaemia in COVID-19 patients in intensive care unit (ICU). It was a single-centre study, 62 COVID-19 patients participated. Change in CRP, serum ferritin, LDH, serum creatinine, haemoglobin between day one and day three of ICU admission were noted. Outcome in terms of in-hospital mortality was noted. Hyperchloremia (>106mmol/L) or rise in chloride by > 5mmol/L was seen in 13/62 (20.96%) patients. It was not associated with a rise in CRP, ferritin, LDH, creatinine, drop in hemoglobin within 72 hours or in-hospital mortality. 44/62 (71%) patients survived and were discharged from hospital. Multivariate logistic regression showed that if age and gender are also considered, there is a 25 times higher chance of having had a significant ferritin rise (> 95 ng/mL) in 72 hours of ICU admission among those who died. (p=0.01). Hyperchloremia (>106mmol/L) or a rise in chloride by > 5mmol/L in 72 hours of ICU admission was not associated with a significant increase in CRP, LDH, ferritin, serum creatinine within 72 hours of ICU admission or mortality in moderate-severe COVID-19 patients. If age and gender are taken into consideration, there is a 25 times higher chance of having had a significant ferritin rise (> 95 ng/mL) in 72 hours of ICU admission among those who died.

Primary hyperparathyroidism (PHPT) usually presents with hypercalcemia related symptoms and signs. Kidneys play an important role in calcium homeostasis. PHPT has been reported to be associated with hyperchloremia, defective urinary acidification, and renal tubular acidosis (RTA). The dysfunction of distal renal tubules is proposed to be secondary to calcium deposition in distal tubules. This case report highlights an initial presentation of parathyroid adenoma as hypokalemia due to distal RTA secondary to medullary nephrocalcinosis.

Objectives:Hyperchloremia has been associated with increased morbidity and mortality in critically ill patients. While previous research has demonstrated an association between hypertonic saline and hyperchloremia, limited data exist in neurocritical care patients. The objective of this study is to