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Purpose Elevated serum bromide levels can cause dermatological, gastrointestinal, and neurological abnormalities. As bromide and chloride are both halogens, bromide may interfere with chloride assays, causing a falsely high serum chloride concentration and a low or negative anion gap. There is a paucity of data describing bromide toxicity from high doses of pyridostigmine bromide (PB). This case report describes a patient with an elevated bromide level with neurological symptoms from a therapeutic dose of PB. Summary A 37-year-old male with myasthenia gravis secondary to type B2 thymoma following thymectomy presented in myasthenic crisis. He required mechanical ventilation and was managed with steroids, intravenous immune globulin, plasmapheresis, and PB. On day 9, the patient experienced acute agitation. He had an anion gap of 2 mEq/L and a chloride concentration of 109 mEq/L. The plasma creatinine concentration was 0.63 to 1.15 mg/dL and urine output was 0.76 to 1.79 mL/kg/h throughout his admission. All other laboratory values were normal. The daily dose of PB was 660 mg on day 9, but the patient received 76 mg of intravenous PB over the first few days of his admission with the largest dose in 24 hours equal to 48 mg. On day 10, the patient's bromide level was 37 μg/mL. His agitation was initially managed with quetiapine, followed by PB dose reduction. To our knowledge, there are 2 cases in the literature of bromide toxicity secondary to PB. These patients experienced neurological symptoms with bromide levels of 88 to 90 μg/mL. Bromide concentrations of more than 12 μg/mL are associated with a higher risk of neuronal dysfunction demonstrated as disturbances on an electroencephalogram, and levels greater than 50 μg/mL are considered toxic. While our patient's bromide level was not as high as those previously reported, no other causes for his agitation were identified. Conclusion Elevated bromide levels from therapeutic PB can occur, and monitoring of these levels should be considered. [ABSTRACT FROM AUTHOR]

Background: Previous research found that serum chloride is an independent predictor of hospital mortality; its increase within 48 hours of admission was linked to a higher percentage of 0.9% saline administration. Furthermore, the number of days that a patient survived was negatively connected with the extent of the serum chloride elevation. So we aimed to predict the outcome among critically ill patients admitted to the surgical intensive care unit in Zagazig University Hospitals and its association with serum chloride fluctuations on admission and within 5 days of intensive care unit stay. Methods: This prospective cohort study was conducted on 300 critically ill patients with an age over 18 years old in the Surgical Intensive Care Unit (SICU), Faculty of Medicine, Zagazig University hospitals. Serum chloride level was measured on admission, 3rd day, and 5th day. According to chloride level on admission, the patients were classified into 3 groups: Group 1 included patients with chloride levels <95 mEq/L, Group 2 included patients with chloride levels 95-105 mEq/L, and Group 3 included patients with chloride levels > 105 mEq/L. Results: Longer periods of stay in the intensive care unit were correlated with higher serum chloride levels at admission (24.33 ± 26.87 days). On ICU admission, patients with hypochloremia had a high death rate (19.3%). Positive fluctuation of serum chloride after admission was linked to a high mortality rate (11.4%). Conclusion: Changes in the serum chloride level endanger the clinical outcome of critically ill patients in the form of longer periods of ICU stay and higher rates of mortality. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Prerenal acute kidney injury (AKI) is associated with profound hypovolemia and reduced renal perfusion. Results regarding hyperchloremia-associated AKI in patients with DKA are conflicting; we therefore investigated the potential relationship between hyperchloremia status and the risk of developing AKI. This single-center cohort study included 113 newly diagnosed T1DM patients with DKA admitted to the pediatric intensive care unit. Laboratory parameters, including Na, K, urea, creatinine, and chloride levels, were retrospectively reviewed at the time of presentation and at 12, 24 and 36 h. AKI was defined using the eGFR according to the pediatric RIFLE classification criteria. Twenty-two (19.5%) of the 113 patients were in the AKI group. Two-way repeated-measures ANOVA showed significant (P values ≤ 0.01) time interaction effects within the groups based on the eGFR and the serum chloride, hyperchloremia, and phosphate levels. Serum chloride levels did not differ between the groups during the first 12 h (p > 0.05) but were significantly greater in the AKI group than in the non-AKI group at 24 h and 36 h (p < 0.01). The final DKA resolution time was significantly greater in the AKI group than in the non-AKI group [22.2 (9.5) vs. 17.0 (12.0) h, respectively; p = 0.03]. However, the groups had similar lengths of hospital stay [13.0 (8.0) days vs. 12.0 (4.0) days, respectively; p = 0.17]. Conclusions: Hyperchloremia may be iatrogenic rather than causative during treatment. This may worsen renal failure and prolong the recovery and treatment time for DKA patients. What is Known? • Acute kidney injury resulting from severe volume depletion is a common occurrence in diabetic ketoacidosis and typically requires significant volume replacement therapy. • In recent years, hyperchloremia has been associated with increased risks of AKI, morbidity, and mortality in some conditions, such as diabetic ketoacidosis. What is New? • The incidence of hyperchloremia increases over time during the treatment of diabetic ketoacidosis. • Hyperchloremia may be an iatrogenic element rather than a cause of acute kidney injury during the treatment of diabetic ketoacidosis. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this therapeutic update is to provide pharmacists with a general overview of the pathophysiology of hyperchloremia and describe strategies to help prevent development of this electrolyte abnormality in hospitalized patients. Summary Hyperchloremia is an electrolyte abnormality associated with an increased incidence of acute kidney injury and metabolic acidosis. Intravenous (IV) fluids utilized for volume resuscitation, medication diluents, and total parental nutrition all may contribute to the development of hyperchloremia. Current evidence suggests that administration of balanced crystalloids for either fluid resuscitation or maintenance fluids may impact serum chloride levels and patient outcomes. In multiple randomized controlled trials, administering balanced crystalloids for fluid resuscitation in critically ill patient populations did not decrease mortality. However, further analyses of subpopulations within these trials have demonstrated that patients with sepsis may benefit from receiving balanced crystalloids for initial fluid resuscitation. Results from several small studies suggest that altering the composition of these IV fluids may help prevent development of hyperchloremia. Conclusion Management of hyperchloremia is preventative in nature and can be mitigated through management of resuscitation fluids, medication diluents, and total parenteral nutrition. Inpatient pharmacists should be aware of the potential risk of fluid-associated hyperchloremia and assist with optimal fluid management to prevent and manage hyperchloremia. [ABSTRACT FROM AUTHOR]

Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient. [ABSTRACT FROM AUTHOR]

Abstract Oral poisoning can trigger diverse physiological reactions, determined by the toxic substance involved. One such consequence is hyperchloremia, characterized by an elevated level of chloride in the blood and leads to kidney damage and impairing chloride ion regulation. Here, we conducted a comprehensive genome-wide analysis to investigate genes or proteins linked to hyperchloremia. Our analysis included functional enrichment, protein–protein interactions, gene expression, exploration of molecular pathways, and the identification of potential shared genetic factors contributing to the development of hyperchloremia. Functional enrichment analysis revealed that oral poisoning owing hyperchloremia is associated with 4 proteins e.g. Kelch-like protein 3, Serine/threonine-protein kinase WNK4, Serine/threonine-protein kinase WNK1 and Cullin-3. The protein–protein interaction network revealed Cullin-3 as an exceptional protein, displaying a maximum connection of 18 nodes. Insufficient data from transcriptomic analysis indicates that there are lack of information having direct associations between these proteins and human-related functions to oral poisoning, hyperchloremia, or metabolic acidosis. The metabolic pathway of Cullin-3 protein revealed that the derivative is Sulfonamide which play role in, increasing urine output, and metabolic acidosis resulted in hypertension. Based on molecular docking results analysis it found that Cullin-3 proteins has the lowest binding energies score and being suitable proteins. Moreover, no major variations were observed in unbound Cullin-3 and all three peptide bound complexes shows that all systems remain compact during 50 ns simulations. The results of our study revealed Cullin-3 proteins be a strong foundation for the development of potential drug targets or biomarker for future studies.

Background: Acute kidney injury (AKI) is a recognized comorbidity in pediatric diabetic ketoacidosis (DKA), although the exact etiology is unclear. The unique physiology of DKA makes dehydration assessments challenging, and these patients potentially receive excessive amounts of intravenous fluids (IVF). We hypothesized that dehydration is over-estimated in pediatric DKA, leading to over-administration of IVF and hyperchloremia that worsens AKI. Methods: Retrospective cohort of all DKA inpatients at a tertiary pediatric hospital from 2014 to 2019. A total of 145 children were included; reasons for exclusion were pre-existing kidney disease or incomplete medical records. AKI was determined by change in creatinine during admission, and comparison to a calculated baseline value. Linear regression multivariable analysis was used to identify factors associated with AKI. True dehydration was calculated from patients' change in weight, as previously validated. Fluid over-resuscitation was defined as total fluids given above the true dehydration. Results: A total of 19% of patients met KDIGO serum creatinine criteria for AKI on admission. Only 2% had AKI on hospital discharge. True dehydration and high serum urea levels were associated with high serum creatinine levels on admission (p = 0.042; p < 0.001, respectively). Fluid over-resuscitation and hyperchloremia were associated with delayed kidney recovery (p < 0.001). Severity of initial AKI was associated with cerebral edema (p = 0.018). Conclusions: Dehydration was associated with initial AKI in children with DKA. Persistent AKI and delay to recovery was associated with hyperchloremia and over-resuscitation with IVF, potentially modifiable clinical variables for earlier AKI recovery and reduction in long-term morbidity. This highlights the need to re-address fluid protocols in pediatric DKA. [ABSTRACT FROM AUTHOR]

Hyperchloremia and hypernatremia are associated with higher mortality in ischemic stroke, but it remains unclear whether their influence directly contributes to ischemic injury. We investigated the impact of 0.9% sodium chloride (154 mM NaCl), 0.9% sodium acetate (167 mM CH3COONa), and their different combinations (3:1, 2:1, and 1:1) on microglial (HMC-3) and neuronal (differentiated SH-SY5Y) survival during oxygen–glucose deprivation/reperfusion (OGD/R). Further, we assessed the effect of hyperchloremia and hypernatremia-treated and OGD/R-induced HMC-3-conditioned media on differentiated SH-SY5Y cells under OGD/R conditions. We performed cell viability, cell toxicity, and nitric oxide (NO) release assays and studied the alteration in expression of caspase-1 and caspase-3 in different cell lines when exposed to hyperchloremia and hypernatremia. Cell survival was decreased in 0.9% NaCl, 0.9% CH3COONa, combinations of HMC-3 and differentiated SH-SY5Y, and differentiated SH-SY5Y cells challenged with HMC-3-conditioned media under normal and OGD/R conditions. Under OGD/R conditions, differentiated SH-SY5Y cells were less likely to survive exposure to 0.9% NaCl. Expression of caspase-1 and caspase-3 in HMC-3 and differentiated SH-SY5Y cells was altered when exposed to 0.9% NaCl, 0.9% CH3COONa, and their combinations. A total of 0.9% NaCl and 0.9% CH3COONa and their combinations decreased the NO production in HMC-3 cells under normal and OGD/R conditions. Both hypernatremia and hyperchloremia reduced the survival of HMC-3 and differentiated SH-SY5Y cells under OGD/R conditions. Based on the OGD/R in vitro model that mimics human ischemic stroke conditions, it possibly provides a link for the increased death associated with hyperchloremia or hypernatremia in stroke patients. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) is a serious complication that affects millions of individuals globally and presents significant health complications. Hyperchloremia, an electrolyte imbalance characterized by high levels of chloride in the blood, may result in gastrointestinal problems, kidney damage, and even death, especially in DKA patients. Early detection and treatment of hyperchloremia are of utmost importance in the management of DKA. This study explores the potential of the bootstrap aggregating ensemble with random subspaces machine learning approach to predict the occurrence of hyperchloremia, providing a basis for early intervention and improved patient outcomes. We tested our approach with the retrospective MIMIC-III database containing 1177 DKA patients and compared it with previous studies with an area under the curve (AUC) of 100%. Our approach showed significant performance outperforming other methods. The combination of this approach may enhance the early detection and timely intervention of hyperchloremia cases, ultimately leading to improved patient outcomes and a more effective management of DKA-associated complications. Our work aims to contribute to the development of decision support tools for healthcare professionals, assisting them in making informed decisions for DKA patients, with a focus on preventing and managing hyperchloremia.

ABSTRACT BACKGROUND: Hyperchloremia is often encountered due to the frequent administration of intravenous fluids in critically ill patients with conditions such as shock or hypotension in the pediatric intensive care unit, and high serum levels of chloride are associated with poor clinical outcomes. OBJECTIVES: This study aimed to determine the association between hyperchloremia and in-hospital mortality in pediatric patients with major trauma. DESIGN AND SETTING: This retrospective cohort study was conducted at a tertiary university hospital in Turkey. METHODS: Data were collected between March 2020 and April 2022. Patients aged 1 month to 18 years with major trauma who received intravenous fluids with a concentration > 0.9% sodium chloride were enrolled. Hyperchloremia was defined as a serum chloride level > 110 mmol/L. Clinical and laboratory data were compared between the survivors and nonsurvivors. RESULTS: The mortality rate was 23% (n = 20). The incidence of hyperchloremia was significantly higher in nonsurvivors than in survivors (P = 0.05). In multivariate logistic analysis, hyperchloremia at 48 h was found to be an independent risk factor for mortality in pediatric patients with major trauma. CONCLUSIONS: In pediatric patients with major trauma, hyperchloremia at 48-h postadmission was associated with 28-day mortality. This parameter might be a beneficial prognostic indicator.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution (n = 351) versus 0.9% saline (n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusionrelated AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization. [ABSTRACT FROM AUTHOR]

Normal saline (N/S) and Ringer’s-Lactate (L/R), are administered in everyday clinical practice. Despite that, N/S increases the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R has lower sodium content, significantly less chloride and contains lactates. In this study we compare the efficacy of L/R versus N/S administration in patients with prerenal acute kidney injury (AKI) and pre-established chronic kidney disease (CKD).

In recent decades, infusion solutions such as NaCl 0.9% and lactate Ringer's solution have been replaced in clinical practice. Since 2017, the national guidelines for perioperative infusion therapy in children recommend balanced isotonic solutions to maintain fluid balance. The composition of balanced infusion solutions varies with respect to their electrolyte content. Hyperchloremia may be mistaken for hypovolemia and may interfere with volume therapy in pediatric patients. Sterofundin ISO® balanced solution contains 127 mmol/L chloride and may cause hyperchloremic acidosis if administered in large volumes. Objectives: The purpose of this study was to compare the effects of Sterofundin ISO® (SF) therapy with the balanced isochloremic solution Deltajonin® (DJ) (106 mmol/L chloride) on the acid–base status in infants undergoing craniofacial surgery. Methods: This retrospective, non-blinded study included 100 infants undergoing craniectomy due to isolated nonsyndromic sagittal craniosynostosis. The first 50 infants received Sterofundin ISO®. Due to changes in national guidelines, the infusion was changed to the isoionic Deltajonin® in an additional 50 infants in 2017. Pre- and postoperative values of chloride, pH, base excess, bicarbonate, and albumin and phosphate were determined, and the strong-ion difference, strong-ion gap, anion gap, and weak acids were calculated. Results: Both groups were comparable in terms of their age, sex, underlying disease, preoperative electrolytes (except K at 3.9 ± 0.3 mmol/L (SF) vs. 4.1 ± 0.3 mmol/L (DJ) and lactate 8.7 ± 2.1 (SF) vs. 9.6 ± 2.6 mmol/L (DJ)). In the Sterofundin ISO® group, hyperchloremic metabolic acidosis was observed in 19 patients, whereas only 2 infants in the Deltajonin® group had hyperchloremic metabolic acidosis. The postoperative chloride level was 111 ± 2.7 mmol/L (SF) vs. 108 ± 2.4 mmol/L (DJ). The difference in anion gap was 12.5 ± 3.0 mmol/L (SF) vs. 14.6 ± 2.8 mmol/L (DJ), and the difference in SIDa (apparent strong-ion difference) was 30.9 mmol/L (SF) vs. 33.8 mmol/L (DJ). Conclusions: Hyperchloremic acidosis can be induced by the volume replacement with high-chloride-concentration crystalloids such as Sterofundin ISO®. This can be detected using the Stewart model. [ABSTRACT FROM AUTHOR]

Despite its known harmful effects, normal saline is still commonly used in the treatment of hypovolemia in polytrauma patients. Given the lack of pre-hospital research on this topic, the current study aims to assess the current practice of fluid administration during the pre-hospital phase of care and its effects on initial metabolic acid-base status in trauma patients. We extracted and completed data from patients recorded in the Lausanne University Hospital (CHUV) trauma registry between 2008 and 2019. Patients were selected according to their age, the availability of a blood gas analysis after arrival at the emergency room, data availability in the trauma registry, and the modality of arrival in the ED. The dominantly administered pre-hospital fluid was normal saline. No association between the type of fluid administered during the pre-hospital phase and the presence of hyperchloremic acidosis in the ED was observed. [ABSTRACT FROM AUTHOR]

Hyperchloremia is a repeated insult in critically ill subjects, leading to more morbidity and mortality. There is a strong relation between hyperchloremia with mortality and morbidity, as renal injury, more extended ICU stay, more mechanical ventilation (MV) period, and other electrolyte disturbances. Our aim is to evaluate the association of hyperchloremia in critically ill subjects with the incidence of mortality and also to study the development of morbidities such as renal injury and electrolyte disturbances and development of metabolic acidosis and its relationship to the period of MV and ICU stay time. A total number of 400 patients subjected to hyperchloremia estimation and laboratory tests were divided into two groups: hyperchloremic group (HG) and non-hyperchloremic group (NHG). The whole incidence of hyperchloremia for the total cohort has been estimated, as well as the whole incidence of mortality, duration of MV, ICU stay time, development of renal injury, and its association with occurrence of metabolic acidosis and electrolyte disturbances among the HG and NHG. The study included 400 patients, 180 of them (45%) were HG, and 220 (55%) were NHG. Mortality was more in 128 HG patients (71.1%), while 48 patients died (21.8%) in NHG (p-value = 0.005). The incidence of morbidities was more in HG than NHG as more; period of MV, ICU stay, renal injury, acidosis and more electrolyte disturbances (p-value < 0.05). Hyperchloremic patients had an increased incidence of mortality. Moreover, they were susceptible to longer mechanical ventilation, ICU stay, renal injury, metabolic acidosis, and electrolytes disorders.

Introduction: hyperchloremia and hypernatremia are common complications in critically ill children and have been associated with the development of acute kidney injury (AKI) and mortality. Objective: to estimate the incidence of hyperchloremia and hypernatremia during the first 72 hours of admission to a pediatric intensive care unit (PICU), and to evaluate their association with AKI and mortality. Material and methods: prospective cohort study, conducted over a period of 15 months. Patients with disorders in plasma levels of chloride (Cl-) or sodium (Na+), as well as with AKI at the time of admission, were excluded. Values > 110 mEq/L Cl- and > 145 mEq/L Na+ were considered as hyperchloremia and hypernatremia, respectively. A sample size of 255 patients was calculated. Statistical analysis. Odds Ratio (OR) and 95% confidence intervals (95% CI) were calculated for bivariate and multivariate analyses. Results: among 241 patients, the incidence of hyperchloremia was 12.4% (n = 30), and of hypernatremia 18.6% (n = 45). The frequency of AKI was 35.6%, and mortality was 14.1%. In logistic regression analysis, hypernatremia was associated with AKI (OR 2.7, 95% CI 1.3-5.7, p < 0.006), but not with mortality. While hyperchloremia was not identified as a risk for AKI or death. Conclusions: hyperchloremia and hypernatremia are common in critically ill pediatric patients, but only hypernatremia seems to confer a higher risk of complications. [ABSTRACT FROM AUTHOR]

Background : Hyperchloremia has been associated with acute kidney injury (AKI) in critically ill adult patients. Data is limited in pediatric patients. Our study sought to determine if an association exists between hyperchloremia and AKI in pediatric patients admitted to the intensive care unit (PICU). Methods: This is a single-center retrospective cohort study of pediatric patients admitted to the PICU for greater than 24 h and who received intravenous fluids. Patients were excluded if they had a diagnosis of kidney disease or required kidney replacement therapy (KRT) within 6 h of admission. Exposures were hyperchloremia (serum chloride ≥ 110 mmol/L) within the first 7 days of PICU admission. The primary outcome was the development of AKI using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included time on mechanical ventilation, new KRT, PICU length of stay, and mortality. Outcomes were analyzed using multivariate logistic regression. Results: There were 407 patients included in the study, 209 in the hyperchloremic group and 198 in the non-hyperchloremic group. Univariate analysis demonstrated 108 (51.7%) patients in the hyperchloremic group vs. 54 (27.3%) in the non-hyperchloremic group (p = <.001) with AKI. On multivariate analysis, the odds ratio of AKI with hyperchloremia was 2.24 (95% CI 1.39–3.61) (p =.001). Hyperchloremia was not associated with increased odds of mortality, need for KRT, time on mechanical ventilation, or length of stay. Conclusion: Hyperchloremia was associated with AKI in critically ill pediatric patients. Further pediatric clinical trials are needed to determine the benefit of a chloride restrictive vs. liberal fluid strategy. [ABSTRACT FROM AUTHOR]

Hyperchloremia has negative consequences, such as increased proinflammatory mediators, renal dysfunction, and mortality in patients with septic shock. However, data on the effects of hyperchloremia on COVID-19 infections are scarce. The study aimed to investigate the effects of hyperchloremia on inflammatory markers, serum creatinine, hemoglobin levels, and outcomes in critically ill COVID-19 patients. A retrospective review of all adult patients admitted to the ICU at King Fahd University Hospital with a moderate to severe COVID-19 infection from January 2020 to August 2021 was performed. Serum chloride levels, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP), creatinine, and hemoglobin levels were collected on the first and third days of ICU admission. Demographic data, oxygen support modality, ICU length of stay (ICU LOS), renal replacement therapy (RRT), and deaths were collected. Of 420 patients, 255 were included; 97 (38%) had hyperchloremia, while 158 (62%) did not. Hyperchloremic patients had a higher percentage of increases in ferritin (54.6%), CRP (6.2%), and LDH (15.5%) between the first and third days of admission, compared to non-hyperchloremic patients (43.7%, 6.3%, and 5.7%, respectively). The decrease in hemoglobin levels was similar in both groups (p=0.103). There was a significant association between hyperchloremia and an increase in serum creatinine (p<0.0001). Sixty-six (68%) patients required endotracheal intubation in the hyperchloremic group (p=0.003). The mortality rate was significant in the hyperchloremic cohort (p=<0.0001). Hyperchloremia was significantly associated with increased risks of kidney injury, endotracheal intubation, and death. However, hyperchloremia was not associated with increased ferritin, CRP, or hemoglobin decreases in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Purpose: Acute kidney injury (AKI) is an established complication of adult traumatic brain injury (TBI) and known risk factor for mortality. Evidence demonstrates an association between hyperchloremia and AKI in critically ill adults but studies in children are scarce. Given frequent use of hypertonic saline in the management of pediatric TBI, we believe the incidence of hyperchloremia will be high and hypothesize that it will be associated with development of AKI. Methods: Single-center retrospective cohort study was completed at an urban, level 1 pediatric trauma center. Children > 40 weeks corrected gestational age and < 21 years of age with moderate or severe TBI (presenting GCS < 13) admitted between January 2016 and December 2021 were included. Primary study outcome was presence of AKI (defined by pediatric Kidney Disease: Improving Global Outcomes criteria) within 7 days of hospitalization and compared between patients with and without hyperchloremia (serum chloride ≥ 110 mEq/L). Results: Fifty-two children were included. Mean age was 5.75 (S.D. 5.4) years; 60% were male (31/52); and mean presenting GCS was 6 (S.D. 2.9). Thirty-seven patients (71%) developed hyperchloremia with a mean peak chloride of 125 (S.D. 12.0) mEq/L and mean difference between peak and presenting chloride of 16 (S.D. 12.7) mEq/L. Twenty-three patients (44%) developed AKI; of those with hyperchloremia, 62% (23/37) developed AKI, while among those without hyperchloremia, 0% (0/15) developed AKI (difference 62%, 95% CI 42–82%, p < 0.001). Attributable risk of hyperchloremia leading to AKI was 62.2 (95% CI 46.5–77.8, p = 0.0015). Conclusion: Hyperchloremia is common in the management of pediatric TBI and is associated with development of AKI. Risk appears to be associated with both the height of serum chloride and duration of hyperchloremia. [ABSTRACT FROM AUTHOR]

Hyperchloremia and hypernatremia are associated with higher mortality in ischemic stroke, but it remains unclear whether their influence directly contributes to ischemic injury. We investigated the impact of 0.9% sodium chloride (154 mM NaCl), 0.9% sodium acetate (167 mM CH3COONa), and their different combinations (3:1, 2:1, and 1:1) on microglial (HMC-3) and neuronal (differentiated SH-SY5Y) survival during oxygen–glucose deprivation/reperfusion (OGD/R). Further, we assessed the effect of hyperchloremia and hypernatremia-treated and OGD/R-induced HMC-3-conditioned media on differentiated SH-SY5Y cells under OGD/R conditions. We performed cell viability, cell toxicity, and nitric oxide (NO) release assays and studied the alteration in expression of caspase-1 and caspase-3 in different cell lines when exposed to hyperchloremia and hypernatremia. Cell survival was decreased in 0.9% NaCl, 0.9% CH3COONa, combinations of HMC-3 and differentiated SH-SY5Y, and differentiated SH-SY5Y cells challenged with HMC-3-conditioned media under normal and OGD/R conditions. Under OGD/R conditions, differentiated SH-SY5Y cells were less likely to survive exposure to 0.9% NaCl. Expression of caspase-1 and caspase-3 in HMC-3 and differentiated SH-SY5Y cells was altered when exposed to 0.9% NaCl, 0.9% CH3COONa, and their combinations. A total of 0.9% NaCl and 0.9% CH3COONa and their combinations decreased the NO production in HMC-3 cells under normal and OGD/R conditions. Both hypernatremia and hyperchloremia reduced the survival of HMC-3 and differentiated SH-SY5Y cells under OGD/R conditions. Based on the OGD/R in vitro model that mimics human ischemic stroke conditions, it possibly provides a link for the increased death associated with hyperchloremia or hypernatremia in stroke patients.

Background: Hyperchloremia is associated with increased mortality in critically ill patients. The objective of this study was to investigate the association between increased chloride levels and mortality outcomes in intracerebral hemorrhage (ICH) patients admitted to the intensive care unit (ICU). Methods: We performed a retrospective study of all patients diagnosed with ICH and included in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ) from 2001 to 2012. Inclusion criteria were the first diagnosis of ICH, ICU length of stay (LOS) over 72 h, and not receiving hypertonic saline treatment. Serum chloride perturbation within 72 h of admission was evaluated as a predictor of outcomes. The increase in chloride from baseline was dichotomized based on an increase in chloride in 72 h (≤5 mmol/L or >5 mmol/L). The primary outcome was 90-day mortality. Results: A total of 376 patients (54.5% male, median age 70 years, interquartile range:58–79 years) were included. The overall 90-day mortality was 32.2% (n=121), in-hospital mortality was 25.8% (n=97), and Day 2 acute kidney injury (AKI) occurred in 29.0% (n=109) of patients. The prevalence of hyperchloremia on admission, during the first 72 h, and an increase in chloride (>5 mmol/L) were 8.8%, 39.4%, and 42.8%, respectively. After adjusting for confounders, the hazard ratio of increase in chloride (>5 mmol/L) was 1.66 (95% confidence interval:1.05–2.64, P=0.031). An increase in chloride (>5 mmol/L) was associated with a higher odds ratio for 90-day mortality in both the AKI and non-AKI groups. Conclusions: An increase in chloride from baseline is common in adult patients with ICH admitted to ICU. The increase is significantly associated with elevated mortality. These results support the significance of diligently monitoring chloride levels in these patients.

Jiaqi Lu,1 Zhili Qi,2 Jingyuan Liu,1 Pei Liu,2 Tian Li,2 Meili Duan,2 Ang Li3 1Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Meili Duan, Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Xicheng District, Beijing, 10005, People’s Republic of China, Email dmeili@ccmu.edu.cn Ang Li, Beijing Ditan Hospital, Capital Medical University, #8 Jing Shun East St, Chaoyang, Beijing, 100015, People’s Republic of China, Email liang@ccmu.edu.cnPurpose: This study aims to investigate the effect of serum chloride and sodium ions on AKI occurrence in ICU patients, and further constructs a prediction model containing these factors to explore the predictive value of these ions in AKI.Methods: The clinical information of patients admitted to ICU of Beijing Friendship Hospital Affiliated to Capital Medical University was collected for retrospective analysis. Logistic regression analysis was used to analyzing the influencing factors. A nomogram for predicting AKI risk was constructed with R software and validated by repeated sampling. Afterwards, the effectiveness and accuracy of the model were tested and evaluated.Results: A total of 446 cases met the requirements of this study, of which 178 developed AKI during their stay in ICU, with an incidence rate of 39.9%. Hypernatremia, heart failure, sepsis, APACHE II score, and initial creatinine value and BE value at ICU admission before the diagnosis of AKI were identified as independent risk factors for developing AKI during ICU stay. These predictors were incorporated into the nomogram of AKI risk in critically ill patients, which was constructed by using R software. Receiver operating characteristic curve analysis was further used and showed that the area under the curve of the model was 0.7934 (95% CI 0.742– 0.8447), indicating that the model had an ideal value. Finally, further evaluated its clinical effectiveness. The clinical effect curve and decision curve showed that most areas of the decision curve of this model were greater than 0, indicating that this model owned a certain clinical effectiveness.Conclusion: The nomogram based on hypernatremia, heart failure, sepsis, APACHE II score, and initial creatinine and BE value in ICU can predict the individualized risk of AKI with satisfactory distinguishability and accuracy.Keywords: intensive care unit, acute kidney injury, hypernatremia, hyperchloremia

Introduction: Serum chloride (Cl−) is a crucial extracellular anion with significant medical importance. Hypochloremia has been identified as an autonomous predictor of mortality based on emerging evidence gathered from patients diagnosed with kidney or heart disease. However, an overabundance of chloride ions (Cl−) can lead to fatality in critically unwell individuals. The objective of the research was to assess the frequency of hyperchloremia among deceased patients, with the aim of modifying our clinical approach by replacing chloride-rich solutions with solutions containing appropriate chloride levels (such as lactated ringer or plasmalyte) to prevent this iatrogenic complication. This may have potential benefits for our patients in the future. Methods: This prospective study was conducted at the Indira Gandhi Institute of Medical Sciences, Patna over a period of one year, from October 2021 to November 2022. This study comprised a sample size of 100 patients who were classified into two distinct groups based on their medical diagnosis. Results: The study's findings indicate that among the Non sepsis Groups, patients aged 80 years accounted for 8.0%. The findings of the study indicate that there was no statistically significant variance in the average Chloride Value across the various time intervals. Conclusion: The administration of chloride-rich solutions in ICU patients necessitating large volume fluid resuscitation should be approached with caution to mitigate the effects of hyperchloremia.

Objective: To investigate the association of point‐of‐care biochemical variables obtained during CPR or within 24 hours of return of spontaneous circulation (ROSC) with patient outcomes. Design: Retrospective study. Setting: University teaching hospital. Animals: Ninety‐four dogs and 27 cats undergoing CPR according to the Reassessment Campaign on Veterinary Resuscitation guidelines. Interventions: None. Measurements and Main Results: Blood gas, acid–base, electrolyte, glucose, and plasma lactate values obtained during CPR or within 24 hours of ROSC were retrospectively evaluated and are described. The blood sample type and collection time with respect to CPR initiation and ROSC were recorded. Measured variables, collection times, and species were included in a multivariable logistic regression model to estimate the odds ratio (OR) and 95% confidence interval of ROSC, sustained ROSC (≥20 min), and survival to hospital discharge. Significance was set at P < 0.05. Seventy‐two venous blood samples obtained during CPR and 45 first venous and arterial blood samples obtained after ROSC were included in logistic regression analysis. During CPR, PvO2 (1.09 [1.036–1.148], P = 0.001) and venous standard base excess (SBE) (1.207 [1.094–1.331], P < 0.001) were associated with ROSC. PvO2 (1.075 [1.028–1.124], P = 0.002), SBE (1.171 [1.013–1.353], P = 0.032), and potassium concentration (0.635 [0.426–0.946], P = 0.026) were associated with sustained ROSC. Potassium concentration (0.235 [0.083–0.667], P = 0.007) was associated with survival to hospital discharge. Following ROSC, pH (69.110 [4.393–1087], P = 0.003), potassium concentration (0.222 [0.071–0.700], P = 0.010), and chloride concentration (0.805 [0.694–0.933], P = 0.004) were associated with survival to hospital discharge. Conclusions: Biochemical variables such as PvO2, SBE, and potassium concentration during CPR and pH, potassium, and chloride concentration in the postarrest period may help identify dogs and cats with lower odds for ROSC or survival to hospital discharge following CPR. [ABSTRACT FROM AUTHOR]

Aim: Hyperchloremia is related to the risks of several morbidities and mortality in seriously sick cases. The effect of hyperchloremia on the incidence of acute kidney injury (AKI) in trauma patients is not well known. Association of hyperchloremia and AKI within the first 72 hour of pediatric intensive care unit (PICU) admission in pediatric trauma patients was investigated. Materials and Methods: A total of 137 patients with major trauma were investigated retrospectively from tertiary hospital. Serum chloride levels = 110 mmol/L described as hyperchloremia. Clinical and laboratory data were compared between AKI and non-AKI. A multivariate logistic regression analysis was used to determine the association between hyperchloremia and AKI. Results: Totally 109 children were favorable for evaluation following the application of suitability criteria. On admission and at 72 hours, electrolyte measurements were similar between two groups, however chloride level was significantly higher in AKI group (112.33 ± 4.74 vs. 109.07 ± 4.90 mmol/L; p<0.01) at 72 hours. Ratio of hyperchloremia was remarkably more common in AKI group (p<0.01). Hyperchloremia at 72 hours was ensured as an independent risk factor for AKI of pediatric patients with major trauma in the multivariate logistic analysis. Conclusion: Hyperchloremia frequently seen among major trauma patients adopted to the PICU, and appear to be related to an increased risk for AKI within the first 72 hour of admission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Hyperchloremia is a repeated insult in critically ill subjects, leading to more morbidity and mortality. There is a strong relation between hyperchloremia with mortality and morbidity, as renal injury, more extended ICU stay, more mechanical ventilation (MV) period, and other electrolyte disturbances. Our aim is to evaluate the association of hyperchloremia in critically ill subjects with the incidence of mortality and also to study the development of morbidities such as renal injury and electrolyte disturbances and development of metabolic acidosis and its relationship to the period of MV and ICU stay time. A total number of 400 patients subjected to hyperchloremia estimation and laboratory tests were divided into two groups: hyperchloremic group (HG) and non-hyperchloremic group (NHG). The whole incidence of hyperchloremia for the total cohort has been estimated, as well as the whole incidence of mortality, duration of MV, ICU stay time, development of renal injury, and its association with occurrence of metabolic acidosis and electrolyte disturbances among the HG and NHG. The study included 400 patients, 180 of them (45%) were HG, and 220 (55%) were NHG. Mortality was more in 128 HG patients (71.1%), while 48 patients died (21.8%) in NHG (p-value = 0.005). The incidence of morbidities was more in HG than NHG as more; period of MV, ICU stay, renal injury, acidosis and more electrolyte disturbances (p-value < 0.05). Hyperchloremic patients had an increased incidence of mortality. Moreover, they were susceptible to longer mechanical ventilation, ICU stay, renal injury, metabolic acidosis, and electrolytes disorders. [ABSTRACT FROM AUTHOR]

Abstract 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.

The classical transurethral resection syndrome as described with monopolar prostate resection has become rare since the switch to bipolar resection and even more so since the introduction of HoLEP. We report a case of a 74-year-old male patient who presented with an irrigation fluid absorption syndrome during a HoLEP for benign prostate hypertrophy. Biochemically this presented as metabolic acidosis and hyperchloremia instead of hyponatremia. He was treated with diuretics and had a swift recovery.

Despite its known harmful effects, normal saline is still commonly used in the treatment of hypovolemia in polytrauma patients. Given the lack of pre-hospital research on this topic, the current study aims to assess the current practice of fluid administration during the pre-hospital phase of care and its effects on initial metabolic acid-base status in trauma patients. We extracted and completed data from patients recorded in the Lausanne University Hospital (CHUV) trauma registry between 2008 and 2019. Patients were selected according to their age, the availability of a blood gas analysis after arrival at the emergency room, data availability in the trauma registry, and the modality of arrival in the ED. The dominantly administered pre-hospital fluid was normal saline. No association between the type of fluid administered during the pre-hospital phase and the presence of hyperchloremic acidosis in the ED was observed.

Background: On the basis of increased mortality associated with hyperchloremia among critically ill patients, we investigated the effect of occurrence of early hyperchloremia on death or disability at 90 days in patients with intracerebral hemorrhage (ICH). Methods: We analyzed the data from Antihypertensive Treatment of Cerebral Hemorrhage 2 trial, which recruited patients with spontaneous ICH within 4.5 h of symptom onset. Patients with increased serum chloride levels (110 mmol/L or greater) at either baseline or 24, 48, or 72 h after randomization were identified. We further graded hyperchloremia into one occurrence or two or more occurrences within the first 72 h. Two logistic regression analyses were performed to determine the effects of hyperchloremia on (1) death within 90 days and (2) death or disability at 90 days after adjustment for potential confounders. Results: Among the total of 1,000 patients analyzed, hyperchloremia within 72 h was seen in 114 patients with one occurrence and in 154 patients with two or more occurrences. Patients with one occurrence of hyperchloremia (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1–5.5) and those with two or more occurrences (OR 2.6, 95% CI 1.3–5.0) had significantly higher odds of death within 90 days after adjustment for age, race and ethnicity, National Institutes of Health Stroke Scale score strata, hematoma volume, presence or absence of intraventricular hemorrhage, cigarette smoking, previous stroke, and maximum hourly dose of nicardipine. Patients with two or more occurrences of hyperchloremia (OR 3.4, 95% CI 2.1–5.6) had significantly higher odds of death or disability at 90 days compared with patients without hyperchloremia after adjustment for the abovementioned potential confounders. Conclusions: The independent association between hyperchloremia and death or disability at 90 days suggests that avoidance of hyperchloremia may reduce the observed death or disability in patients with ICH. Clinical Trial Registration: ClinicalTrials.gov: NCT01176565. [ABSTRACT FROM AUTHOR]

Background/aim: While chloride (Cl) is the most abundant anion in the serum, it is unfortunately one of the most commonly disregarded laboratory test results routinely drawn upon admission into the medical intensive care unit (MICU). We aimed to investigate the relation between in-hospital mortality, different pathologies requiring admission to the MICU, serum Cl levels, and other biochemical tests in a tertiary center. Materials and methods: The prospective study included data from 373 patients admitted to the ICU of a tertiary care center between 2017 and 2019. Data of patients under 18, pregnant patients or patients who were in the MICU for under 48 h were excluded. Comorbidity status, complete blood count, biochemistry tests, and blood gas analysis results of all patients included in the study were collected and recorded. Univariate and multivariate analyses were performed with the obtained data. Results: Of the patients included in the study, 158 (42.4%) were discharged, and 215 (57.6%) died. In the receiver operator characteristics curve analysis performed to determine the discriminating power of Cl levels with a cut-off value of >98 mEq/L in relation to mortality, its sensitivity was found to be 84% and specificity 60%. According to Kaplan-Meier analysis results, mortality rate was higher (60% vs 46%) and survival time was lower (19.0 ± 1.46 vs. 23.0 ± 4.36 days; p = 0.035) in the patient group with high Cl levels compared to the patient group with normal or low Cl levels. In the Cox regression analysis, it was found that the survival time of the patients hospitalized in the MICU was associated with the variables of Cl, presence of cancer diagnosis and pCO2 (hazard ratio: 1.030 (1.008-1.049), 2.260 (1.451-3.500), and 1.020 (1.003-1.029); p < 0.05, respectively). Conclusion: Mortality in MICU patients were found to increase in association with higher Cl levels at admission, presence of cancer disease, and higher pCO2 levels. In addition, it should not be ignored that there may be an important relationship between renal failure and hyperchloremia in MICU patients. [ABSTRACT FROM AUTHOR]

Background: 0.9% saline commonly used for resuscitation of septic patients might induce biochemical changes leading to detrimental effects. Ringer's lactate being a balanced crystalloid might be beneficial in such a scenario. Objectives: We undertook this study to explore in detail the effect of these fluids in the resuscitation of septic patients, and risks and benefits these two fluids would have on the overall prognosis of patients. Methods: This was an open-label randomized controlled trial undertaken in emergency medical services attached to the department of medicine at a tertiary care teaching hospital. One hundred sixty adult (⩾18 years old) medical patients admitted with the diagnosis of sepsis fulfilling eligibility criteria were included. They were randomly assigned to receive 0.9% saline or ringer's lactate. These fluids were given for the initial 24 h only, and after then, the type of fluid given was based on treating physician discretion. Various biochemical parameters were measured at baseline and various time points during the hospital stay. The primary outcome was to find out the incidence of hyperchloremia at 24 h from the time of randomization and during the hospital stay. The secondary outcomes were incidence of acute kidney injury, need for renal replacement therapy; differences in pH, bicarbonate, serum lactate, coagulation parameters, sequential organ failure assessment scores at various time points; and hospital/30-day mortality. Results: The baseline characteristics in both groups were comparable. At admission, each group had a serum chloride value which was comparable (p value: 0.595); however, at 24 and 48 h, a statistically significant difference was noticed, with 0.9% saline group having a higher mean serum chloride value (113.66 ± 10.04 v/s 108.98 ± 8.04 mEq/L, p value: 0.001 at 24 h) and (114.75 ± 9.51 v/s 111.12 ± 7.84 mEq/L, p value: 0.022 at 48 h). At 24 and 48 h post-randomization, the incidence of hyperchloremia was significantly higher in the 0.9% saline group (at 24 h, 0.9% saline: 75.0% v/s Ringer's lactate: 48.8%, p value: 0.001 and at 48 h, 0.9% saline: 77.2% v/s Ringer's lactate: 60.3%, p value: 0.022), although there was no difference in the incidence of hyperchloremia recorded during the hospital stay. Acute kidney injury incidence at 24 and 48 h post-randomization was significantly higher in the 0.9% saline group (at 24 h, 0.9% saline: 23.8% v/s Ringer's lactate: 10.0%, p value: 0.020 and at 48 h, 0.9% saline: 29.1% v/s Ringer's lactate: 15.4%, p value: 0.039). No significant differences in other secondary outcomes were observed. Conclusion: Higher incidence of hyperchloremia and a higher rate of acute kidney injury at 24 and 48 h after randomization were noted in the 0.9% saline group. [ABSTRACT FROM AUTHOR]

Background: A few previous clinical studies have shown that chloride (Cl) contributes to the progression and development of hypertension or proteinuria. Therefore, we aimed to determine whether hyperchloremia is associated with hypertension or proteinuria in patients with chronic kidney disease (CKD) and to define the relationships between the reduction in serum Cl concentration associated with CKD treatment and improvements in hypertension and/or proteinuria. Methods: We performed a retrospective observational study of new or referred patients with CKD who had hyperchloremia, moderate proteinuria, renal dysfunction, and hypertension. Patients taking medication for metabolic acidosis or with a history of dialysis were excluded. The participants' systolic and diastolic blood pressure (BP), serum sodium (Na) and Cl concentrations, and urinary protein (UP) concentration were measured at baseline and after 1 month of CKD treatment. Results: Fifty-one patients with CKD were included in the study. Their serum Cl concentration independently correlated with sBP and UP at baseline (P = 0.022 and P = 0.033, respectively). After 1 month's CKD treatment, their serum Na and Cl concentrations, sBP, and UP were significantly lower. The change in sBP during the month (ΔsBP) correlated with the change in serum Cl (ΔCl) (P = 0.012) but not with the change in serum Na. Multivariate analysis showed that ΔsBP was independently associated with ΔCl (P = 0.029). Conclusions: Hyperchloremia is an independent predictor of hypertension and proteinuria for patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Large volume resuscitation with normal saline (NS) may be associated with iatrogenic hyperchloremia and renal injury. Objective: The purpose of this study was to assess clinical outcomes associated with the use of Lactated Ringer's (LR) compared to NS as resuscitative fluid in diabetic ketoacidosis (DKA). Methods: Single-center, retrospective analysis of patients admitted for DKA. The primary objective of this study was to evaluate the incidence of iatrogenic hyperchloremia associated with fluid resuscitation using balanced crystalloid compared to NS. Results: Iatrogenic hyperchloremia occurred more frequently in the NS group compared to the LR group (74.4% vs 64.2%; P = 0.05). Mean maximum serum chloride was higher in the NS group (115.7 mmol/L vs 113.7 mmol/L; P = 0.004). Incidence of hypernatremia was higher in the NS group (18.3% vs 9.3%; P = 0.02). There was no significant difference in the incidence of AKI; however, mean change in serum creatinine at 48 hours showed a significantly greater decrease in the LR group (-0.15 mg/dL vs -0.04 mg/dL; P = 0.002). No significant differences were found in intensive care unit (ICU) length of stay or total hospital length of stay. Conclusion and Relevance: This study found a statistically significant reduction in the incidence of iatrogenic hyperchloremia with the use of LR compared to NS as fluid resuscitation in DKA. Serum creatinine was more improved in the LR group versus NS group at 48 hours. Preferential use of balanced crystalloid for fluid resuscitation in DKA may reduce incidence of hyperchloremia and support renal recovery in this population. [ABSTRACT FROM AUTHOR]

Abstract 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 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

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