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.
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.
CONCLUSIONS: 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.
UNASSIGNED: 2014-001005-41; date of registration: 28/10/2014.
UNASSIGNED: EC project number 2014/038.

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.

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.

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.

BACKGROUND: 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.
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).
CONCLUSIONS: 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.

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).
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.
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).
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.

Background The importance of optimal acid-base balance during renal transplant surgeries cannot be stressed enough. Optimal preload and electrolyte balance is important in maintaining this. There has been a debate on the choice of perioperative crystalloids in renal transplant surgeries over the past decades. Normal saline (0.9% saline) is more likely to cause hyperchloremic acidosis when compared to balanced salt solutions (BSS) with low chloride content whereas BSS may cause hyperkalemia. We aim to compare the safety and efficacy of normal saline (NS), Ringer\'s lactate (RL) and Plasmalyte (PL) on acid-base balance and electrolytes during living donor kidney transplantation. Materials and methods Patients were randomized to NS group (n = 60), RL group (n = 60) and Plasmalyte group (n = 60). Arterial blood samples were collected for acid-base analysis after induction of anaesthesia (T0), prior to clamping the iliac vein (T1), 10 minutes after reperfusion of the donated kidney (T2) and at the end of surgery (T3). In addition, serum creatinine and 24-hour urine output were recorded on postoperative days one, two and seven. Results There was a statistically significant difference (p < 0.001) in the pH at the end of surgery between the three groups with the NS group being more acidotic (pH 7.29 ± 0.06, 95% CI 7.27-7.32), although this was not clinically relevant. This was explainable by the parallel increase in chloride in the NS group. Early postoperative graft functions in terms of serum creatinine, urine output and graft failure requiring dialysis were not significantly different between the groups. Conclusion Balanced salt solutions such as Plasmalyte and Ringer\'s lactate are associated with better pH and chloride levels compared to normal saline when used intraoperatively in renal transplant patients. This difference, however, does not appear to have any bearing on graft function. Plasmalyte seems to maintain a better acid-base and electrolyte balance, especially during the postreperfusion period.

OBJECTIVE: 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.
OBJECTIVE: Retrospective, single-center study.
METHODS: Tertiary care hospital.
METHODS: Adult patients who underwent cardiovascular surgery with CPB.
METHODS: None.
RESULTS: 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).
CONCLUSIONS: 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.

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