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Introduction: 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. Methods: 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. Results: 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. Conclusion: 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 [ABSTRACT FROM AUTHOR]

Hyperchloremia is a potential risk factor for acute kidney injury (AKI) in critically ill patients. However, the relationship between hyperchloremia and postoperative AKI in adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB) remains unclear. The authors aimed to determine whether postoperative hyperchloremia was associated with postoperative AKI in these populations. Retrospective, single-center study. Tertiary care hospital. Adult patients who underwent cardiovascular surgery with CPB. None. Patients with and without postoperative hyperchloremia were matched (1:1). The primary outcome was the rate of postoperative AKI diagnosed using the Kidney Disease: Improving Global Outcomes consensus criteria. Postoperative hyperchloremia was defined as postoperative serum chloride levels of >110 mmol/L during the first 48 hours. An increase in serum chloride levels (Δ[Cl–]) was defined as the difference between the preoperative and maximum postoperative serum chloride levels during the first 48 hours ([Cl–] max). Propensity-score matching and univariate and multivariate logistic regression analyses were employed. A total of 323 patients were included. Propensity-score matching selected 55 pairs for the final comparison. The incidence of postoperative AKI did not differ between the two groups (47% v 46%, p = 1.0). In the multivariate logistic regression analysis, Δ[Cl–] was associated independently with the development of postoperative AKI (odds ratio, 1.13; 95% confidence interval, 1.06-1.21; p < 0.001). Exposure to postoperative hyperchloremia was not associated with postoperative AKI in adult patients undergoing cardiovascular surgery with CPB. However, an increase in the serum chloride level might be associated with postoperative AKI. [ABSTRACT FROM AUTHOR]

Abstract Background The debate for the optimum sodium concentration in the rehydration solution in diabetic ketoacidosis (DKA) persists till the moment. The aim was to compare the outcome of 0.9% saline versus 0.45% saline in children with moderate and severe (DKA) regarding the effect on serum electrolytes, duration of DKA resolution and the incidence of hyperchloremia. Results A retrospective analysis of 121 children with moderate or severe DKA was done. After the initial 4 h in which both groups received normal saline, patients were divided into two groups continuing on 0.9% (N=72) or switched to 0.45% saline (N=49). Serum chloride and Cl/Na ratios were significantly higher in 0.9% saline group at 4 and 8 h. The 0.9% saline group had significantly higher proportion of hyperchloremia at 4 and 8 h (P value: 0.002, 0.02). The median duration of correction of DKA (14 h among 0.9% saline versus 10 h among 0.45% saline) without significant difference (P value= 0.43). The change in plasma glucose, effective osmolarity, corrected Na levels were comparable between groups. Conclusion There is an unavoidable iatrogenically induced rise in serum chloride with higher incidence of hyperchloremia with the use of normal saline in rehydration of children presenting in DKA and shock. The use of 0.45% saline as post-bolus rehydration fluid is not associated with a decline in the corrected serum sodium concentration and does not affect the rate of correction of acidosis or rate of drop in blood glucose or duration of DKA resolution when compared to normal saline.

Background: Recent technological advancements have enabled the use of electrolyte solutions such as saline or buffered electrolyte solution during transurethral resection or laser enucleation of the prostate. However, saline absorption may cause hyperchloremic metabolic acidosis. Case presentation: A male in his late seventies underwent holmium laser enucleation of the prostate under a combination of subarachnoid block and general anesthesia. Intraoperatively, abdominal distension prompted the attending anesthesiologist to consider the possibility of SGA malposition, and the trachea was intubated. Oropharyngeal and neck edema was observed, and laboratory examination revealed considerable acidosis with hyperchloremia. Further evaluation confirmed the absorption of a large amount of saline into the circulation via the perforated bladder. Application of the simplified Stewart approach clearly suggested that hyperchloremia was the principal cause of metabolic acidosis. The dilution of albumin attenuated acidosis. Conclusions: Absorption of normal saline during laser enucleation of prostate caused hyperchloremic metabolic acidosis and airway edema. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 60-year-old man with mental confusion and signs of dehydration. Topics include attending physician then requesting whole blood sodium measured using a point-of care device; and patient describing in the case study presenting with hypertonic dehydration resulting in electrolyte abnormalities most notable for hypernatremia and hyperchloremia.

Abstract 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.

Abstract Background Fluid therapy is a cornerstone of pediatric intensive care medicine. We aimed at quantifying the load of water, sodium and chloride due to different fluid indications in our pediatric intensive care unit (PICU). We were particularly interested in the role of fluid creep, i.e. fluid administered mainly as the vehicle for drugs, and the association between sodium load and water balance. Methods Critically ill children aged ≤3 years and invasively ventilated for ≥48 h between 2016 and 2019 in a single tertiary center PICU were retrospectively enrolled. Need for renal replacement therapy, plasmapheresis or parenteral nutrition constituted exclusion criteria. Quantity, quality and indication of fluids administered intravenously or enterally, urinary output and fluid balance were recorded for the first 48 h following intubation. Concentrations of sodium and chloride provided by the manufacturers were used to compute the electrolyte load. Results Forty-three patients (median 7 months (IQR 3–15)) were enrolled. Patients received 1004 ± 284 ml of water daily (153 ± 36 ml/kg/day), mainly due to enteral (39%), creep (34%) and maintenance (24%) fluids. Patients received 14.4 ± 4.8 mEq/kg/day of sodium and 13.6 ± 4.7 mEq/kg/day of chloride, respectively. The majority of sodium and chloride derived from fluid creep (56 and 58%). Daily fluid balance was 417 ± 221 ml (64 ± 30 ml/kg/day) and was associated with total sodium intake (r2 = 0.49, p

Madeline B Libin, Joel G Weltman, Jennifer Prittie Department of Emergency and Critical Care, Animal Medical Center, New York, NY, USACorrespondence: Madeline B LibinDepartment of Emergency and Critical Care, Animal Medical Center, 510 E. 62nd Street, New York, NY 10065, USATel +1 212 838 8100Fax +1 212 752 2592Email madelinelibin@gmail.comPurpose: To evaluate whole blood chloride concentration and hospital-acquired AKI in hospitalized canine patients. Secondary outcome measures included the volume-adjusted chloride load, in-hospital mortality and length of ICU stay.Patients and Methods: This is a prospective, observational study. Sixty dogs admitted to the ICU and receiving IV fluid therapy for > 24 hours from February 2018 to July 2019. Corrected chloride and creatinine concentrations were obtained twice daily. Total volume of IV fluid and total chloride load were recorded. Volume-adjusted chloride load (VACL) was calculated by dividing the chloride administered by the volume of fluid administered. Hospital-acquired AKI was defined as an increase in creatinine of ≥ 26.5 μmol/L (0.3 mg/dL) or 150% from baseline to maximum. Survival to hospital discharge or non-survival and ICU length of stay were also recorded.Results: Fifteen out of 60 patients developed hospital-acquired AKI. Maximum corrected chloride was significantly different in AKI group (median 122.3 mmol/L) vs non-AKI group (median 118.1 mmol/L; p=0.0002). Six out of 60 patients developed hyperchloremia. Hyperchloremic patients were significantly more likely to develop in-hospital AKI (p=0.03). Patients hospitalized ≥ 2 days had a significantly higher [Cl−]max compared to those with shorter ICU stay (121.8 ± 5.9 mmol/L vs 117.5 ± 4.3 mmol/L; p=0.002). Eight out of 60 patients were non-survivors. Maximum corrected chloride and creatinine concentrations were not significantly different between survivors and non-survivors. VACL was not significantly different between AKI or mortality groups.Conclusion: Maximum corrected chloride concentration was significantly higher in dogs with hospital-acquired AKI, even amongst dogs without hyperchloremia. Additionally, maximum corrected chloride concentrations were significantly higher in dogs hospitalized in the ICU longer compared to those hospitalized for fewer than two days. There was no significant difference in VACL in any of the outcome groups. Results from this study suggest alterations in chloride may be observed alongside the development of acute kidney injuries. Future studies in critically ill dogs are warranted.Keywords: acute kidney injury, IV fluid, electrolytes, hyperchloremia, volume-adjusted chloride load

Abstract 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

Background: Serum chloride (Cl−) is one of the most essential extracellular anions. Based on emerging evidence obtained from patients with kidney or heart disease, hypochloremia has been recognized as an independent predictor of mortality. Nevertheless, excessive Cl− can also cause death in severely ill patients. This study aimed to investigate the relationship between hyperchloremia and high mortality rate in patients admitted to the surgical intensive care unit (SICU). Methods: We enrolled 2131 patients from the Multiparameter Intelligent Monitoring in Intensive Care III database version 1.4 (MIMIC-III v1.4) from 2001 to 2012. Selected SICU patients were more than 18 years old and survived more than 72 h. A serum Cl− level ≥ 108 mEq/L was defined as hyperchloremia. Clinical and laboratory variables were compared between hyperchloremia (n = 664) at 72 h post-ICU admission and no hyperchloremia (n = 1467). The Locally Weighted Scatterplot Smoothing (Lowess) approach was utilized to investigate the correlation between serum Cl- and the thirty-day mortality rate. The Cox proportional-hazards model was employed to investigate whether serum chlorine at 72 h post-ICU admission was independently related to in-hospital, thirty-day and ninety-day mortality from all causes. Kaplan-Meier curve of thirty-day and ninety-day mortality and serum Cl− at 72 h post-ICU admission was further constructed. Furthermore, we performed subgroup analyses to investigate the relationship between serum Cl− at 72 h post-ICU admission and the thirty-day mortality from all causes. Results: A J-shaped correlation was observed, indicating that hyperchloremia was linked to an elevated risk of thirty-day mortality from all causes. In the multivariate analyses, it was established that hyperchloremia remained a valuable predictor of in-hospital, thirty-day and ninety-day mortality from all causes; with adjusted hazard ratios (95% CIs) for hyperchloremia of 1.35 (1.02 ~ 1.77), 1.67 (1.28 ~ 2.19), and 1.39 (1.12 ~ 1.73), respectively. In subgroup analysis, we observed hyperchloremia had a significant interaction with AKI (P for interaction: 0.017), but there were no interactions with coronary heart disease, hypertension, and diabetes mellitus (P for interaction: 0.418, 0.157, 0.103, respectively). Conclusion: Hyperchloremia at 72 h post-ICU admission and increasing serum Cl− were associated with elevated mortality risk from all causes in severely ill SICU patients. [ABSTRACT FROM AUTHOR]

Background: Chloride (Cl) is required for the regulation of blood pressure, renal function, gastrointestinal homeostasis and decarboxylation/gas transport. "Dyschloremia" or levels of serum Cl beyond the normal range, is a frequent occurrence in intensive care units and seems to be mostly caused by iatrogenic procedures (i.e. intravenous infusion of fluids rich in Cl). Hypochloremia and hyperchloremia seem to be related to high risk of death in specified intensive care unit (ICU) groups, although the data is inconclusive. Hyperchloremia may be associated with higher hemodynamic unstable changes and need for vasopressors, in addition to hyperchloremic metabolic acidosis (e.g., following major surgeries). Nonetheless, the direct or indirect mediation of these effects is still uncertain. Additionally, new research suggests that individuals with advanced hyperchloremia have a higher risk of acute renal damage and require renal replacement treatment. Objective: The purpose of this study was to describe significant chloride-related outcomes in critical illness and to evaluate their relevance for everyday clinical practice and therapeutic alternatives. Conclusion: One may conclude that the concern about understanding the impact of chloride disorders on negative outcomes is rising; there seems to be a link between chloride disorders and negative outcomes, particularly death, in the ICU setting; one could theorize the need to rationalize the use of solutions with electrolyte components separate from the physiological solutions; and consider the presence or the development of hyperchloremia as a prognostic factor, without taking into consideration the severity of the critical patient. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Patients with DKA generally present with a high anion gap metabolic acidosis (AG > 16) due to the presence of ketones but may also develop a narrow anion gap metabolic acidosis related to hyperchloremia. This study attempts to determine the incidence of hyperchloremic metabolic acidosis (before starting IV fluids) in children with DKA and to evaluate the impact of hyperchloremic metabolic acidosis on acute kidney injury and cerebral edema and inturn on mortality and duration of PICU stay. Methods: This was a prospective study conducted in the Department of Paediatrics, VIMS, Bellary between May 2016 to December 2017 and a total of 32 patients with DKA were enrolled in the study. Along with routine investigations, ABG and serum chloride levels were measured at the time of admission for categorization into normochloremic (high anion-gap) metabolic acidosis and hyperchloremic (normal anion-gap) metabolic acidosis. Incidence of hyperchloremic metabolic acidosis and its impact on the development of acute kidney injury and cerebral edema was taken as the primary outcome of the study. Mortality rate and duration of PICU stay were taken as a secondary outcome. Results: Hyperchloremic metabolic acidosis was observed in 18.8% of the study group. Acute kidney injury was seen in 38.4% of children who had normochloremic metabolic acidosis and in 83.3% of children with hyperchloremia. About 50% patients developed cerebral edema in the hyperchloremia group and only 3.8% developed cerebral edema in normochloremic group. These differences were statistically significant. Mortality rate in normochloremic and hyperchloremic metabolic acidosis was 3.8% and 50% respectively. Conclusions: Hyperchloremia at presentation in DKA is a risk factor for increased mortality. This fact should be born in mind while treating patients aggressively with chloride-containing fluids. Simple investigations like ABG and serum chloride levels can direct careful management of DKA and appropriate selection of IV fluids. [ABSTRACT FROM AUTHOR]

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 >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 [ABSTRACT FROM AUTHOR]

Abstract Background Recent data suggest that hyperchloremia induced by fluid resuscitation is associated with acute kidney injury (AKI) and mortality, particularly in sepsis. Experimental studies showed that hyperchloremia could affect organ functions. In patients with septic shock, we examined the relationship between serum chloride concentration and both renal function and survival. Methods Post hoc analysis of the “HYPER2S” trial database (NCT01722422) including 434 patients with septic shock randomly assigned for resuscitation with 0.9% or 3% saline. Metabolic parameters were recorded up to 72 h. Metabolic effects of hyperchloremia (> 110 mmol/L) were studied stratified for hyperlactatemia (> 2 mmol/L). Cox models were constructed to assess the association between chloride parameters, day-28 mortality and AKI. Results 413 patients were analysed. The presence of hyperlactatemia was significantly more frequent than hyperchloremia (62% versus 71% of patients, respectively, p = 0.006). Metabolic acidosis was significantly more frequent in patients with hyperchloremia, no matter the presence of hyperlactatemia, p

Abstract Background The plasma ionized calcium concentration (cCa2+) represents the biologically active form of calcium and is the preferred method for evaluating calcium status in animals. Different pH‐corrective equations have been developed for human plasma, but the validity of the equations for bovine plasma is unknown. Hypothesis We hypothesized that pH‐corrective equations for bovine plasma would be similar to those used for human plasma; cCa2+ was dependent on the plasma concentrations of total calcium (cTCa), chloride (cCl), L‐lactate (cLactate), and albumin (cAlbumin); and the in vitro and in vivo cCa2+‐pH relationships would differ. Animals Ten healthy calves (in vitro study), 1426 critically ill calves. Methods The in vitro plasma log10(cCa2+)‐pH relationship was determined by CO2 tonometry of 465 plasma samples. Plasma cCl was altered by equivolume dilution of plasma with 3 electrolyte solutions of different cCl. The in vivo plasma cCa2+‐pH relationship was investigated and validated using clinicopathologic data extracted from the medical records of 950 (model development) and 476 (model validation) critically ill calves. Results pH‐corrective equations for bovine plasma were similar to those used for human plasma. Plasma cCa2+ increased in vitro with increases in plasma cCl. Plasma cCa2+ in critically ill calves was associated with plasma cTCa, blood pH, plasma cCl, serum cMg, and cL‐lactate (R2 = 0.69) but not plasma cAlbumin. Conclusions and Clinical Importance Calculation of cCa2+ from cTCa in calf plasma or serum requires adjustment for at least pH and cCl when 1 or both are outside the reference range.

Abstract 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 (

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. [ABSTRACT FROM AUTHOR]

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 < 7.35) and 55 with alkalemia (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 < 0.001; low SIDa: 15 days vs. 12 days, P = 0.015; increased AG: 16 days vs. 11 days, P < 0.001; low BE: 14 days vs. 13 days, 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. [ABSTRACT FROM AUTHOR]

Objective: To determine the significance and impact of additional chloride testing as part of a diagnostic laboratory test battery for borderline primary hyperparathyroidism (pHPT). Study Design: Retrospective database review of parathyroidectomy patients. Setting: A tertiary care, academic health sciences center. Subjects and Methods: Patients referred to a head and neck endocrine clinic for evaluation and treatment for pHPT. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Septic shock is a lethal disease, and identifying high-risk patients through noninvasive and widely available biomarkers can help improve global outcomes. While the clinical impact of chloride levels on critically ill patients remains unclear, this study aims to investigate the association between hypochloremia and mortality following ICU admission among septic shock patients., Methods: This is an analysis of data stored in the databases of Medical Information Mart for Intensive Care IV (MIMIC-IV). The initial chloride levels were classified ashypochloremia, normal chloraemia, and hyperchloraemia. A multivariate logistic regression model was applied, adjusting for age, lactate, pH, PO2, urine volume, RDW, creatinine, and liver disease, to assess the association between the three categories of chloride levels and mortality., Results: Of 3726 patients included in the study, 470 patients (12.6%) had hypochloremia on ICU admission. During the follow-up period, 1120 (33.5%) patients died. Hypochloremia was significantly associated with increased mortality and the incidence of AKI after adjusting for several variables., Conclusions: Hypochloremia is independently associated with higher hospital mortality, AKI incidence among septic shock patients. However, further high-quality research is necessary to establish the precise relationship between hypochloremia and septic shock prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI. Methods A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl− concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl− concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia. Discussion In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl− content on serum Cl− concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl− concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia. Trial registration Clinicaltrials.gov, NCT03204955. Registered on 28 June 2017.

Abstract 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 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.

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. [ABSTRACT FROM AUTHOR]

Objective: Hyperchloremia is associated with worsened outcomes in various clinical situations; however, data are limited in patients with diabetic ketoacidosis (DKA). The purpose of this study was to determine the effect of hyperchloremia on time to DKA resolution. Methods: We conducted a retrospective cohort study of adult patients admitted with incident DKA from January 2013 through October 2017 and stratified by the development of hyperchloremia versus maintaining normochloremia. The primary outcome was time to final DKA resolution. Secondary outcomes included time to initial DKA resolution, incidence of acute kidney injury (AKI) on admission, in-hospital development of AKI, and hospital length of stay (LOS). Results: Of the 102 patients included, 52 developed hyperchloremia. Patients with hyperchloremia had longer times to final DKA resolution compared to those with normochloremia (median 22.3 [interquartile range, IQR, 15.2-36.9] vs 14.2 [IQR 8.8-21.1] hours; P = .001). Time to initial DKA resolution was also longer in patients who developed hyperchloremia compared to those who did not (median 16.3 vs 10.9 hours; P = .024). More patients with hyperchloremia developed in-hospital AKI (26.9% vs 8.0%; P = .01). Median hospital LOS was significantly longer in the hyperchloremia cohort (P < .001). On Cox regression analysis, time to DKA resolution was significantly longer with each 1 mmol/L increase in serum chloride (HR 0.951; P < .001). Conclusion: The presence of hyperchloremia in patients with DKA was associated with increased time to DKA resolution, risk of in-hospital AKI, and hospital LOS. Further evaluation of the avoidance or treatment of hyperchloremia in DKA is needed. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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]). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Serum chloride derangements are associated with poor clinical outcomes, including acute kidney injury (AKI) and mortality. We sought to determine the association between persistent hyperchloremia and renal recovery in critically ill children with AKI. Methods: We performed a retrospective cohort study of all patients with day 2 AKI admitted to a large academic pediatric intensive care unit from January 2014 to December 2015. After applying exclusion criteria, 348 patients were categorized as (1) hyperchloremia on both day 2 and day 7 (PersistentCl), (2) hyperchloremia on day 2 with normochloremia on day 7 (RecoveredCl), (3) normochloremia on day 2 with hyperchloremia on day 7 (DelayedCl), and (4) no hyperchloremia on day 2 nor day 7 (NormalCl). Hyperchloremia was defined as ≥ 110 mEq/L. The primary outcome was renal recovery on day 7, defined as the absence of AKI criteria. Secondary outcomes included discharge renal recovery, mortality, duration of mechanical ventilation, and hospital length of stay. Results: Day 7 renal recovery rates for PersistentCl, RecoveredCl, DelayedCl, and NormalCl were 37%, 66%, 71%, and 52% respectively. PersistentCl had lower odds of day 7 renal recovery (aOR = 0.29; 95% CI, 0.14 to 0.60; p = 0.0009), lower odds of discharge renal recovery (aOR = 0.22; 95% CI, 0.11 to 0.48; p = 0.0001), and higher odds of mortality (aOR = 3.50; 95% CI, 1.11 to 11.10; p = 0.03) when compared with RecoveredCl after adjusting for confounders. Conclusions: Persistent hyperchloremia is independently associated with impaired renal recovery as well as higher mortality. Prospective studies are indicated to determine if serum chloride represents a modifiable risk factor for poor outcomes. [ABSTRACT FROM AUTHOR]

In this article, the second in a new series designed to improve acute care nurses' understanding of laboratory abnormalities, the author continues her discussion of important values in the basic metabolic panel (see Back to Basics, January, for a discussion of sodium and fluid balance). Here she addresses the electrolytes potassium and chloride as well as blood urea nitrogen and creatinine, four values that are best considered together because they both reflect and impact renal function as well as acid--base homeostasis. Important etiology, clinical manifestations, and treatment concerns are also presented. Three case studies are used to integrate select laboratory diagnostic tests with history and physical examination findings, allowing nurses to develop a thorough, focused plan of care for electrolyte abnormalities and kidney disorders commonly encountered in the medical--surgical setting. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that large-volume infusions of 0.9% sodium chloride (NaCl) for resuscitation are associated with hyperchloremic metabolic acidosis, renal vasoconstriction, and increased risk of acute kidney injury (AKI). Patients with neurological injury may require hypertonic NaCl for therapeutic hypernatremia, treatment of cerebral salt wasting, hyponatremia, or elevated intracranial pressure. Consequently, this increased exposure to chloride may result in an increased risk for development of AKI. Objective: The primary aim of this study was to describe the risk for development of AKI in neurologically injured patients receiving large volumes of intravenous hypertonic NaCl. Methods: This single-center, retrospective study looked at neurologically injured patients who received hypertonic NaCl and sodium acetate. Data were collected to assess renal function, hyperchloremia, and acidemia. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive association between the amount of daily and overall chloride exposure and development of AKI. Results: A total of 301 patients were screened, and of those, 142 were included. Of the 142 patients included, 13% developed AKI, and 38% developed hyperchloremia. Additionally, 32% of patients were switched from NaCl to sodium acetate after an average of 3.4 ± 1.5 days of NaCl therapy. The ROC curve demonstrated that if patients received greater than 2055 mEq of chloride over 7 days, they were more likely to develop AKI (sensitivity 72%, specificity 70%; P = 0.002; area under the curve = 0.7). Conclusion and Relevance: Neurologically injured patients receiving hypertonic sodium therapy with a high chloride load are at risk of developing hyperchloremia and AKI. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

The aim of this observational retrospective cohort study was to analyze the association between hyperchloremia and serum chloride variation with in-hospital acute kidney injury (AKI) and mortality in a general, no-ICU hospitalized population. We performed a retrospective study on inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 2010 and December 2014 with inclusion of adult patients with at least two values available for chloride, sodium and creatinine. Hyperchloremia was defined as serum chloride concentration ≥ 108 mmol/L (moderate hyperchloremia: chloremia between 108-110 mmol/L, severe hyperchloremia: chloremia > 110 mmol/L). According to the time of onset of the electrolyte disturbance, hyperchloremia was then classified as hospital acquired (HA) and community acquired (CA). In patients with HA-hyperchloremia, chloride variation (ΔCl) was calculated. In-hospital AKI was defined according to creatinine kinetics criteria occurring 48 h after hospital admission. Logistic regression analysis was used to evaluate the association between the exposures of interest and in-hospital AKI and mortality. A total of 24,912 hospital admissions met the inclusion criteria. Regression analyses showed that only severe HA-hyperchloremia was associated with increased risk of in-hospital AKI [odds ratio (OR) 2.60, 95% confidence interval (CI) 1.58, 4.30, p value < 0.001] and death (OR 3.89, 95% CI 2.11, 7.18, p value < 0.001). With increasing ΔCl, the OR of in-hospital AKI increased progressively (p value for trend = 0.005). In conclusion, severe hyperchloremia is an independent predictor for in-hospital AKI and mortality; HA-hyperchloremia is more detrimental for patient outcome; higher ΔCl from hospital admission is associated with increased risk of AKI. [ABSTRACT FROM AUTHOR]

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 >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.

Abstract Background Hyperchloremia is common in critically ill septic patients. The impact of hyperchloremia on the incidence of acute kidney injury (AKI) is not well studied. We investigated the association between hyperchloremia and AKI within the first 72 h of intensive care unit (ICU) admission. Methods 6490 ICU adult patients admitted with severe sepsis or septic shock were screened for eligibility. Exclusion criteria included: AKI on admission, baseline estimated glomerular filtration rate (eGFR)

Abstract In response to comments raised, we acknowledge the shortcomings of our study. It is a small study. However, it is a pilot study, which is not meant to create generalizable data, rather to explore new potential directions. To this end, our conclusions were clearly supported by the results. We demonstrated that administration of 16.4% NaCl/Na-acetate solution was feasible, safe, and was associated with lower rates of AKI. We share the call that large RCTs are required to follow this pilot study and hope that our data will stimulate the ongoing discussion regarding the role of chloride in AKI mechanism.

Hyperchloremia is elevation of serum cholesterol level above normal (> 200 mg/dl). There are an association between cardiovascular diseases and high level of blood cholesterol. There are many risk factors of hypercholesterolemia as genetic, environmental, systematic disease as diabetes mellites and some drugs factors. A cross sectional study was conducted on adults who were attending Samara general hospital outpatients clinicduring the period from 5th February‑30th April 2017. The information regarding the problem and demographic characterestics of persons was obtained according to a questionnaire and the weight, height, blood pressure, total blood cholesterol level was recorded. The results shows that the frequency of hypercholesterolemia among sample study was (54%). There is no significant association between frequency of hypercholesterolemia according to gender, age group, body mass index, family history and smoking habit but it has been reported that a significant association between high serum cholesterol and presence of hypertension, cardiac diseases and diabetes mellites. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders.Methods: We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints.Findings: We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601-2137) more positive in the Na154 arm (p < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 (p = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI - 0.2-30.4%, p = 0.05).Conclusions: In adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia. [ABSTRACT FROM AUTHOR]

Back ground: Hyperchloremia is elevation of serum cholesterol level above normal (> 200 mg/dl). There are an association between cardiovascular diseases and high level of blood cholesterol. There are many risk factors of hypercholesterolemia as genetic, environmental, systematic disease as diabetes mellites and some drugs factors. Subjects and method: A cross sectional study was conducted on adults who were attending Samara general hospital outpatients clinic during the period from 5th February-30th April 2017. The information regarding the problem and demographic characterestics of persons was obtained according to a questionnaire and the weight, height, blood pressure, total blood cholesterol level was recorded. Results: The frequency of hypercholesterolemia among sample study was (54%). There is no significant association between frequency of hypercholesterolemia according to gender, age group, body mass index, family history and smoking habit but it has been reported that a significant association between high serum cholesterol and presence of hypertension, cardiac diseases and diabetes mellites. [ABSTRACT FROM AUTHOR]

Background: The plasma ionized calcium concentration (cCa2+) represents the biologically active form of calcium and is the preferred method for evaluating calcium status in animals. Different pH‐corrective equations have been developed for human plasma, but the validity of the equations for bovine plasma is unknown. Hypothesis: We hypothesized that pH‐corrective equations for bovine plasma would be similar to those used for human plasma; cCa2+ was dependent on the plasma concentrations of total calcium (cTCa), chloride (cCl), L‐lactate (cLactate), and albumin (cAlbumin); and the in vitro and in vivo cCa2+‐pH relationships would differ. Animals: Ten healthy calves (in vitro study), 1426 critically ill calves. Methods: The in vitro plasma log10(cCa2+)‐pH relationship was determined by CO2 tonometry of 465 plasma samples. Plasma cCl was altered by equivolume dilution of plasma with 3 electrolyte solutions of different cCl. The in vivo plasma cCa2+‐pH relationship was investigated and validated using clinicopathologic data extracted from the medical records of 950 (model development) and 476 (model validation) critically ill calves. Results: pH‐corrective equations for bovine plasma were similar to those used for human plasma. Plasma cCa2+ increased in vitro with increases in plasma cCl. Plasma cCa2+ in critically ill calves was associated with plasma cTCa, blood pH, plasma cCl, serum cMg, and cL‐lactate (R2 = 0.69) but not plasma cAlbumin. Conclusions and Clinical Importance: Calculation of cCa2+ from cTCa in calf plasma or serum requires adjustment for at least pH and cCl when 1 or both are outside the reference range. [ABSTRACT FROM AUTHOR]

Introduction: Dextromethorphan hydrobromide is widely available as an over-the-counter cough suppressant. A semi-synthetic opioid displaying N-methyl-d-aspartate receptor antagonism, it is commonly abused for recreational purposes. Spuriously elevated serum chloride concentrations are a well-described phenomenon in the setting of dextromethorphan hydrobromide toxicity, but evidence to suggest the development of tolerance is limited to case reports. Case: A 32-year-old male known to chronically ingest dextromethorphan hydrobromide for recreational purposes presented to regional hospitals on 179 occasions over 110 months and was treated for dextromethorphan toxicity on 163/174 (93.7%) of these visits. He reported a subjective need to increase his dosing over time to achieve the same degree of intoxication. Measured serum chloride over this period (n = 217) ranged from 98 to 138 mEq/L (median 115 mEq/L, IQR 110–123 mEq/L). Measured concentrations over the 110-month period progressively rose, with a fitted plot of 111.15 + 0.00232x describing the rise in measured chloride. Though not formally assessed, anion gaps tended to become progressively more negative over the observed period. Discussion: We report a patient with persistent dextromethorphan hydrobromide abuse at escalating doses whose mean serum chloride concentration increased, on average, by 0.00232 mEq/L every day over a 110-month period. This case demonstrates progressive spurious hyperchloremia secondary to bromide interference in hospital-based chloride assays, supporting the patient's reported need to dose escalate to the same desired effect. Although this artefactual laboratory finding is a well-documented result of bromide ingestion, it may be useful in identifying patterns of dextromethorphan hydrobromide use that suggest tolerance. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a major public health problem that complicates 10 – 40% of hospital admissions. Importantly, AKI is independently associated with increased risk of progression to chronic kidney disease, end-stage renal disease, cardio- vascular events, and increased risk of in-hospital and long-term mortality. The chloride content of intravenous fluid has garnered much attention over the last decade, as well as its association with excess use and adverse outcomes, including AKI. Numerous studies show that changes in serum chloride concentration, independent of serum sodium and bicarbonate, are associated with increased risk of AKI, morbidity, and mortality. This comprehensive review details the complex renal physiology regarding the role of chloride in regulating renal blood flow, glomerular filtration rate, tubuloglomerular feed- back, and tubular injury, as well as the findings of clinical research related to the chloride content of intravenous fluids, changes in serum chloride concentration, and AKI. Chloride is underappreciated in both physiology and pathophysiology. Although the exact mechanism is debated, avoidance of excessive chloride administration is a reason- able treatment option for all patients and especially in those at risk for AKI. Therefore, high-risk patients and those with “incipient” AKI should receive balanced solutions rather than normal saline to minimize the risk of AKI. [ABSTRACT FROM AUTHOR]

Introduction/Objective. Hyperchloremia is often registered in adults’ studies after administration with 0.9% sodium chloride, which contributes to the development of acute kidney injury (AKI) as it leads to vasoconstriction of renal blood vessels. The aim of this study was to determine the correlation of sodium and chloride imbalance with the development of AKI, with consideration of other risk factors for this disorder. Methods. This retrospective study included 146 randomly selected preterm infants hospitalized at the Neonatal Intensive Care Unit from 2008 to 2015. Results. Among the patients registered for the study, 23.97% developed AKI, and they were of a significantly lower gestational age (26.3 ± 2.8 weeks vs. 31.7 ± 2.90 weeks, p < 0.05); birth weight (971.31 ± 412.1 g vs. 1,753.3 ± 750.3 g, p < 0.05); Apgar score in the first (3.2 ± 1.7 vs. 5.7 ± 2.4, p < 0.05) and fifth minute (5.3 ± 1.7 vs. 7.1 ± 1.8, p < 0.05) of life compared to those without AKI. The neonates with AKI had significantly higher maximum chloremia (Clmax: 114.1 ± 8.4 vs. 111.7 ± 4.6, p = 0.029) and maximum natremia (Namax: 147.9 ± 8.8 vs. 142.9 ± 4, p < 0.05). Each of these parameters is (independently) a statistically significant risk factor for the development of AKI, and gestational age is the strongest (OR = 1 / 0.643 = 1.55; 95% CI 1.24–1.94). Mortality in neonates with AKI was higher than in neonates without AKI (19.4% vs. 92.7%, p < 0.05). Conclusion. Hyperchloremia and hypernatremia are more common in the premature newborns with AKI compared to the premature newborns without AKI. Higher maximum sodium and chloride values are independent risk factors for AKI.

Hyperchloremia is a common electrolyte disorder that is associated with a diverse group of clinical conditions. The kidney plays an important role in the regulation of chloride concentration through a variety of transporters that are present along the nephron. Nevertheless, hyperchloremia can occur when water losses exceed sodium and chloride losses, when the capacity to handle excessive chloride is overwhelmed, or when the serum bicarbonate is low with a concomitant rise in chloride as occurs with a normal anion gap metabolic acidosis or respiratory alkalosis. The varied nature of the underlying causes of the hyperchloremia will, to a large extent, determine how to treat this electrolyte disturbance.

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 100–108 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 < 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.

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; ≤96, 97–99, 100–102, 103–105, 106–108, and ≥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 103–105 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 ≤96, 97–99, 100–102, 103–105, 106–108, and ≥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 103–105 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 ≤99 hazard ratio (HR): 1.45 and 1.94 for discharge serum chloride of 97–99 and ≤96 mmoL/L, respectively; p < 0.001) and ≥109 mmoL/L (HR: 1.41; p < 0.001), compared with discharge serum chloride of 103–105 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 100–108 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.