Cullin-3 proteins be a novel biomarkers and therapeutic targets for hyperchloremia induced by oral poisoning.

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 Decreased Microglial and Neuronal Survival during Oxygen-Glucose Deprivation/Reperfusion.

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.

Effect of a single small volume fluid bolus with balanced or un-balanced fluids on chloride and acid-base status: a prospective randomized pilot study (the FLURES-trial).

OBJECTIVE: To compare the short-term effects on acid base, electrolyte status and urine output of a single fluid bolus of saline to that of the balanced solution Plasmalyte® in critically ill patients. METHODS: Prospective, randomized, controlled trial. Adult patients (≥ 18 years) admitted to the ICU receiving a fluid bolus were randomized to receive 1 L of saline (NaCl 0.9%, Baxter) or a balanced fluid [Plasmalyte® (Baxter)]. Blood samples and urine output were collected just before (T0), just after (T1), 2 h after (T2) (only for urinary output) and three hours after termination of the fluid bolus (T4). The effect of fluid boluses on serum chloride, apparent strong ion difference, base excess, urinary output and blood pressure or vasopressor need were analyzed. MAIN RESULTS: Patients who received a 1 L saline fluid bolus had a significant increase in serum chloride (1.60; 95% CI 1.10 to 2.10; P < 0.001) and short-term decrease in apparent strong ion difference (- 1.85; 95% CI - 2.71 to - 0.99; P < 0.001) and base excess (- 0.90; 95% CI - 1.31 to - 0.50; P < 0.001). We observed a 17% increase in patients developing hyperchloremia in the saline group (0.17; 95% CI 0.05 to 0.29; P = 0.005). No significant difference in urinary output, blood pressure or vasopressor need was observed in either group. CONCLUSION: Even a single, small bolus of saline, administered to critically ill patients, causes a significant increase in chloride concentration and a decrease in apparent strong ion difference and base excess, and an increase in the number of patients developing hyperchloremia. No difference in effect on urinary output, blood pressure or vasopressor need was observed between the two groups. EUDRACT NUMBER: 2014-001005-41; date of registration: 28/10/2014. LOCAL EC APPROVAL: EC project number 2014/038.

Iatrogenic hyperchloremia: An overview in hospitalized patients for pharmacists.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. 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.

A balancing act: drifting away from the reflexive use of "ab"normal saline.

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.

The effect of dehydration, hyperchloremia and volume of fluid resuscitation on acute kidney injury in children admitted to hospital with diabetic ketoacidosis.

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.

Effect of hyperchloremia on mortality of pediatric trauma patients: a retrospective cohort study

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.

Comparison of Fluid Replacement with Sterofundin ISO® vs. Deltajonin® in Infants Undergoing Craniofacial Surgery-A Retrospective Study.

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.

Choice of creep or maintenance fluid type and their impact on total daily ICU sodium burden in critically ill patients: A systematic review and meta-analysis.

PURPOSE: Maintenance and hidden/creep fluids are a major source of fluid and sodium intake in intensive care unit (ICU) patients. Recent research indicates that low versus high sodium content maintenance fluids could decrease fluid and sodium burden. We conducted a systematic review (SR) with meta-analysis to summarize the impact of maintenance fluid choice on total daily sodium in ICU patients. MATERIALS AND METHODS: Systematic literature search in Pubmed, Embase, the Cochrane Library and the. CLINICAL TRIALS REGISTRY: Only controlled clinical trials were included. EXCLUSION CRITERIA: trials on resuscitation fluids, performed in the emergency department only and in pediatric patients. Primary objective was the reduction in mean total sodium intake with low versus high sodium content maintenance/creep fluids. RESULTS: Five studies (1105 patients) were included. Heterogeneity was high.Risk of bias was moderate. Mean daily sodium reduction was 117 mmol (95%Confidence Interval [CI] -174; -59; p < 0.001) with low versus high sodium content maintenance/creep fluids. Incidence of hyperchloremia was lower (OR 0.26; 95%CI 0.1; 0.64) with low sodium. There were no differences in the incidences of hyper-/hyponatremia and fluid balances. CONCLUSION: Using low sodium content maintenance/creep fluids substantially reduces daily sodium burden in adult ICU patients. Significant knowledge/research gaps exist regarding relevance and safety. TRIAL REGISTRATION: PROSPERO 2022 CRD42022300577 (February 2022).

Effect of Pre-Hospital Intravenous Fluids on Initial Metabolic Acid-Base Status in Trauma Patients: A Retrospective Cohort Study.

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.

Impact of hyperchloremia on inflammatory markers, serum creatinine, hemoglobin, and outcome in critically ill patients with COVID-19 infection.

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.

Classification of pseudohypoaldosteronism type II as type IV renal tubular acidosis: results of a literature review.

Pseudohypoaldosteronism (PHA) type II (PHA2) is a genetic disorder that leads to volume overload and hyperkalemic metabolic acidosis. PHA2 and PHA type I (PHA1) have been considered to be genetic and pediatric counterparts to type IV renal tubular acidosis (RTA). Type IV RTA is frequently found in adults with chronic kidney disease and is characterized by hyperchloremic hyperkalemic acidosis with normal anion gap (AG). However, we recently observed that PHA1 was not always identical to type IV RTA. In this study, we focused on the acid-base balance in PHA2. Through a literature search published between 2008-2020, 46 molecularly diagnosed cases with PHA2 were identified (median age of 14 years). They comprised 11 sets of familial and 16 sporadic cases and the pathology was associated with mutations in WNK 4 (n = 1), KLHL3 (n = 17), and CUL3 (n = 9). The mean potassium (K+) level was 6.2 ± 0.9 mEq/L (n = 46, range 4.0-8.6 mEq/L), whereas that of chloride (Cl-) was 110 ± 3.5 mEq/L (n = 41, 100-119 mEq/L), with 28 of 41 cases identified as hyperchloremic. More than half of the cases (18/35) presented with metabolic acidosis. Although AG data was obtained only in 16 cases, all but one cases were within normal AG range. Both Cl- and HCO3- levels showed significant correlations with K+ levels, which suggested that the degree of hyperchloremia and acidosis reflect the clinical severity, and is closely related to the fundamental pathophysiology of PHA2. In conclusion, our study confirmed that PHA2 is compatible with type IV RTA based on laboratory findings.

Unexplained Bromide Toxicity Presenting as Hyperchloremia and a Negative Anion Gap.

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.

Normal saline versus balanced crystalloids in patients with prerenal acute kidney injury and pre-existing chronic kidney disease.

INTRODUCTION: 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). METHODS: In this prospective open-label study we included patients with prerenal AKI and previously known CKD stage III-V without need for dialysis. Patients with other forms of AKI, hypervolemia or hyperkalemia were excluded. Patients received either N/S or L/R intravenously at a dose of 20 ml/kg body-weight/day. We studied kidney function at discharge and at 30 days, duration of hospitalization, acid-base balance and the need for dialysis. RESULTS: We studied 38 patients and 20 were treated with N/S. Kidney function improvement during hospitalization and at 30 days after discharge, was similar between the two groups. Duration of hospitalization was also similar. Anion-gap improvement as expressed with Δanion-gap between discharge and admission day was higher in those patients that received L/R in comparison to those that received N/S and pH increase (ΔpH) was slightly higher in the L/R group. No patient required dialysis. CONCLUSIONS: Administration of L/R or N/S to patients with prerenal AKI and pre-established CKD had no significant difference in short or long term kidney function but L/R showed a better profile in acid-base balance improvement and Cl- overload in comparison to N/S.

Hyperchloremia on Admission to Pediatric Intensive Care in Mechanically Ventilated Children is Associated with Impaired Renal Function.

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.

Association of hyperchloremia and acute kidney injury in pediatric patients with moderate and severe traumatic brain injury.

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.

Association of hypochloremia with mortality among patients requiring continuous renal replacement therapy.

BACKGROUND: Serum chloride derangement is common in critically ill patients requiring continuous renal replacement therapy (CRRT). We aimed to assess the association between serum chloride levels before and during CRRT with mortality. METHODS: This is a retrospective cohort study of critically ill patients receiving CRRT for acute kidney injury from December 2006 through November 2015 in a tertiary referral hospital in the United States. We used logistic regression to assess serum chloride before and mean serum chloride during CRRT as predictors for 90 days mortality after CRRT initiation. The normal reference range for serum chloride was 99-108 mmol/L. RESULTS: Of 1282 eligible patients, 25%, 50%, and 25% had hypochloremia, normochloremia, and hyperchloremia, respectively. The adjusted odds ratio for 90 days mortality in patients with hypochloremia before CRRT was 1.82 (95% CI 1.29-2.55). During CRRT, 4%, 70%, 26% of patients had mean serum chloride in the hypochloremia, normochloremia, and hyperchloremia range, respectively. The adjusted odds ratio for 90 days mortality in patients with mean serum chloride during CRRT in the hypochloremia range was 2.96 (95% CI 1.43-6.12). Hyperchloremia before and during CRRT was not associated with mortality. The greater serum chloride range during CRRT was associated with increased mortality (OR 1.29; 95% CI 1.13-1.47 per 5 mmol/L increase). CONCLUSION: Hypochloremia before and during CRRT is associated with higher mortality.

Patient-Specific Risk Factors Associated With the Development of Hyperchloremia in a Neurocritical Care Intensive Care Unit.

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.

Hyperchloremia and association with acute kidney injury in critically ill children.

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. A higher resolution version of the Graphical abstract is available as Supplementary information.

Association of point-of-care blood variables obtained from dogs and cats during cardiopulmonary resuscitation and following return of spontaneous circulation with patient outcomes.

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.