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.

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.

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.
OBJECTIVE: 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.

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.

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.

A high serum bromide level can cause erroneously high serum chloride levels measured through routine assays. Here, we describe a case of pseudohyperchloremia in which routine labs showed a negative anion gap and elevated chloride levels measured with ion-selective assay. The serum chloride level was found to be lower when measured with a chloridometer that employs a colorimetric method of quantification. The initial serum bromide level was elevated at 1100 mg/L that was confirmed by repeating the test that again showed an elevated level of 1600 mg/L and appeared to cause erroneous hyperchloremia when using conventional serum chloride quantification methods. Our case highlights lab errors and factitious hyperchloremia as a cause of the negative anion gap caused by bromism, even without a clear history of bromide exposure. The case also underscores the importance of chloride measurement using both colorimetric methods and ion-selective assay in the case of hyperchloremia.

UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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

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.
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).
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).
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.

To investigate the effect of the occurrence of early hyperchloremia on death or severe disability at 180 days in patients with severe traumatic brain injury (TBI).
METHODS: Post hoc analysis of Resuscitation Outcomes Consortium Hypertonic Saline (ROC HS)-TBI trial.
METHODS: A total of 114 North American emergency medical services agencies in the ROC.
METHODS: A total of 991 patients with severe TBI and Glasgow Coma Scale score of less than or equal to 8.
METHODS: Prehospital resuscitation with single IV dose (250 cc) of 7.5% saline in 6% dextran-70, 7.5% saline (no dextran), or crystalloid.
RESULTS: Patients with increased serum chloride concentrations (110 mmol/L or greater) 24 hours after randomization were identified. Hyperchloremia was graded into one or greater than or equal to 2 occurrences in the first 24 hours. Logistic regression analyses were performed to determine the effects of hyperchloremia on: 1) death or severe disability at 180 days and 2) death within 180 days after adjusting for confounders. Compared with patients without hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death or severe disability at 180 days (odds ratio [OR], 1.81; 95% CI, 1.19-2.75) and death within 180 days (OR, 1.89; 95% CI, 1.14-3.08) after adjustment for confounders. However, the total volume of fluids administered during the first 24 hours was an independent predictor of death within 180 days; therefore, after adding an interaction term between the total volume of fluids administered during the first 24 hours and greater than or equal to 2 occurrences of hyperchloremia, patients with greater than or equal to 2 occurrences of hyperchloremia had significantly higher odds of death within 180 days (OR, 2.35; 95% CI, 1.21-4.61 d) but not of composite outcome of death or severe disability at 180 days.
CONCLUSIONS: After modifying for the effect of the total volume of fluids administered during the first 24 hours, multiple occurrences of hyperchloremia in the first 24 hours were associated with higher odds of death within 180 days in patients with severe TBI.