Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients.
ABSTRACT: Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes.This is a single-center, retrospective cohort study at Mayo Clinic Hospital-Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score.A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96-104) vs. 102 mmol/L (98-105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of ?94 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1-2.6; P = .01).Dyschloremia is common in critically ill patients, and severe hypochloremia is independently associated with an increased risk of development of acute kidney injury.
Project description:We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes.We identified patients who received large-volume fluid resuscitation, defined as greater than 60?mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads.University Medical Center.Patients admitted to ICUs from 2000 to 2008.None.Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or acute kidney injury after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age, and severity (p = 0.0015) over 1 year.Chloride load is associated with significant adverse effects on survival out to 1 year even after controlling for total fluid load, age, and baseline severity of illness. However, the relationship between chloride load and development of hyperchloremic acidosis or acute kidney injury is less clear, and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.
Project description:BACKGROUND:Our objective was to establish the safety of 3% hypertonic saline (HTS) resuscitation for trauma and acute care surgery patients undergoing emergent laparotomy and temporary abdominal closure (TAC) with the hypothesis that HTS administration would be associated with hyperosmolar hypercholoremic acidosis, lower resuscitation volumes, and higher fascial closure rates, without adversely affecting renal function. METHODS:We performed a retrospective cohort analysis of 189 trauma and acute care surgery patients who underwent emergent laparotomy and TAC, comparing patients with normal baseline renal function who received 3% HTS at 30 mL/h (n = 36) to patients with standard resuscitation (n = 153) by baseline characteristics, resuscitation parameters, and outcomes including primary fascial closure and Kidney Disease: Improving Global Outcomes stages of acute kidney injury. RESULTS:The HTS and standard resuscitation groups had similar baseline illness severity and organ dysfunction, though HTS patients had lower serum creatinine at initial laparotomy (1.2 mg/dL vs. 1.4 mg/dL; p = 0.078). Forty-eight hours after TAC, HTS patients had significantly higher serum sodium (145.8 mEq/L vs. 142.2 mEq/L, p < 0.001), chloride (111.8 mEq/L vs. 106.6 mEq/L, p < 0.001), and osmolarity (305.8 mOsm/kg vs. 299.4 mOsm/kg; p = 0.006), and significantly lower arterial pH (7.34 vs. 7.38; p = 0.011). The HTS patients had lower intravenous fluid (IVF) volumes within 48 hours of TAC (8.5 L vs. 11.8 L; p = 0.004). Serum creatinine, urine output, and kidney injury were similar between groups. Fascial closure was achieved for 92% of all HTS patients and 77% of all standard resuscitation patients (p = 0.063). Considering all 189 patients, higher IVF resuscitation volumes within 48 hours of TAC were associated with decreased odds of fascial closure (odds ratio, 0.90; 95% confidence interval, 0.83-0.97; p = 0.003). CONCLUSION:Hypertonic saline resuscitation was associated with the development of a hypernatremic, hyperchloremic, hyperosmolar acidosis, and lower total IVF resuscitation volumes, without adversely affecting renal function. These findings may not be generalizable to patients with baseline renal dysfunction and susceptibility to hyperchloremic acidosis-induced kidney injury. LEVEL OF EVIDENCE:Prognostic study, level II.
Project description:The high chloride content of 0.9% saline leads to adverse pathophysiological effects in both animals and healthy human volunteers, changes not seen after balanced crystalloids. Small randomized trials confirm that the hyperchloremic acidosis induced by saline also occurs in patients, but no clinical outcome benefit was demonstrable when compared with balanced crystalloids, perhaps due to a type II error. A strong signal is emerging from recent large propensity-matched and cohort studies for the adverse effects that 0.9% saline has on the clinical outcome in surgical and critically ill patients when compared with balanced crystalloids. Major complications are the increased incidence of acute kidney injury and the need for renal replacement therapy, and that pathological hyperchloremia may increase postoperative mortality. However, there are no large-scale randomized trials comparing 0.9% saline with balanced crystalloids. Some balanced crystalloids are hypo-osmolar and may not be suitable for neurosurgical patients because of their propensity to cause brain edema. Saline may be the solution of choice used for the resuscitation of patients with alkalosis and hypochloremia. Nevertheless, there is evidence to suggest that balanced crystalloids cause less detriment to renal function than 0.9% saline, with perhaps better clinical outcome. Hence, we argue that chloride-rich crystalloids such as 0.9% saline should be replaced with balanced crystalloids as the mainstay of fluid resuscitation to prevent 'pre-renal' acute kidney injury.
Project description:Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature.Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving ?80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride ?96 mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46; P<0.001) with no incremental contribution from serum sodium (P=0.49). Hypochloremic versus nonhypochloremic patients exhibited renal wasting of chloride (P=0.04) and of chloride relative to sodium (P=0.01), despite better renal free water excretion (urine osmolality 343±101 mOsm/kg versus 475±136; P<0.001). Hypochloremia was associated with poor diuretic response (odds ratio, 7.3; 95% confidence interval, 3.3-16.1; P<0.001). In the interventional pilot, lysine chloride supplementation was associated with an increase in serum chloride levels of 2.2±2.3 mmol/L, and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in amino terminal, pro B-type natriuretic peptide, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio.Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardiorenal parameters.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02031354.
Project description:Background Pulmonary arterial hypertension (PAH) is a lethal disease. In resource-limited countries PAH outcomes are worse because therapy costs are prohibitive. To improve global outcomes, noninvasive and widely available biomarkers that identify high-risk patients should be defined. Serum chloride is widely available and predicts mortality in left heart failure, but its prognostic utility in PAH requires further investigation. Methods and Results In this study 475 consecutive PAH patients evaluated at the University of Minnesota and Vanderbilt University PAH clinics were examined. Clinical characteristics were compared by tertiles of serum chloride. Both the Kaplan-Meier method and Cox regression analysis were used to assess survival and predictors of mortality, respectively. Categorical net reclassification improvement and relative integrated discrimination improvement compared prediction models. PAH patients in the lowest serum chloride tertile (?101 mmol/L: hypochloremia) had the lowest 6-minute walk distance and highest right atrial pressure despite exhibiting no differences in pulmonary vascular disease severity. The 1-, 3-, and 5-year survival was reduced in hypochloremic patients when compared with the middle- and highest-tertile patients (86%/64%/44%, 95%/78%/59%, and, 91%/79%/66%). After adjustment for age, sex, diuretic use, serum sodium, bicarbonate, and creatinine, the hypochloremic patients had increased mortality when compared with the middle-tertile and highest-tertile patients. The Minnesota noninvasive model (functional class, 6-minute walk distance, and hypochloremia) was as effective as the French noninvasive model (functional class, 6-minute walk distance, and elevated brain natriuretic peptide or N-terminal pro-brain natriuretic peptide) for predicting mortality. Conclusions Hypochloremia (?101 mmol/L) identifies high-risk PAH patients independent of serum sodium, renal function, and diuretic use.
Project description:Only a few observational studies investigated the association between hypochloremia and mortality in critically ill patients, and these studies included small number of septic patients. Also, no study has evaluated the effect of an increase in chloride (Cl-) concentration in hypochloremia on the mortality. A total of 843 Korean septic patients were divided into three groups based on their baseline Cl- level, and Cox analyses were performed to evaluate the 28-day mortality. Moreover, the change in Cl- level (?Cl) from baseline to 24, 48, or 72?hour was determined, and Cox analyses were also conducted to evaluate the relationship of ?Cl with mortality. 301 (35.7%) patients were hypochloremic (Cl-?<?97 mEq/L), and 38 (4.5%) patients were hyperchloremic (Cl-?>?110 mEq/L). During the follow-up period, 119 (14.1%) patients died. Hypochloremia was significantly associated with an increased mortality after adjusting for several variables, but an 1 mEq/L increase of ?Cl within 24?hour in patients with hypochloremia was significantly related to a decreased mortality. Caution might be required in severe septic patients with hypochloremia considering their increased mortality rate. However, an increased Cl- concentration might decrease the mortality rate of such patients.
Project description:BACKGROUND: The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting. METHODS: Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111?mmol/l up to and including 154?mmol/l) or lower-chloride (concentration 111?mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling. RESULTS: The search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1.64, 95 per cent c.i. 1.27 to 2.13; P?<?0.001) and hyperchloraemia/metabolic acidosis (RR 2.87, 1.95 to 4.21; P?<?0.001). High-chloride fluids were also associated with greater serum chloride (MD 3.70 (95 per cent c.i. 3.36 to 4.04) mmol/l; P?<?0.001), blood transfusion volume (SMD 0.35, 0.07 to 0.63; P?=?0.014) and mechanical ventilation time (SMD 0.15, 0.08 to 0.23; P?<?0.001). Sensitivity analyses excluding heavily weighted studies resulted in non-statistically significant effects for acute kidney injury and mechanical ventilation time. CONCLUSION: A weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.
Project description:Intravenous fluid therapy is the most common intervention received by acutely ill patients. Historically, saline (0.9% sodium chloride) has been the most frequently administered intravenous fluid, especially in North America. Balanced crystalloid solutions (e.g., lactated Ringer's, Plasma-Lyte) are an increasingly used alternative to saline. Balanced crystalloids have a sodium, potassium, and chloride content closer to that of extracellular fluid and, when given intravenously, have fewer adverse effects on acid-base balance. Preclinical research has demonstrated that saline may cause hyperchloremic metabolic acidosis, inflammation, hypotension, acute kidney injury, and death. Studies of patients and healthy human volunteers suggest that even relatively small volumes of saline may exert physiological effects. Randomized trials in the operating room have demonstrated that using balanced crystalloids rather than saline prevents the development of hyperchloremic metabolic acidosis and may reduce the need for vasopressors. Observational studies among critically ill adults have associated receipt of balanced crystalloids with lower rates of complications, including acute kidney injury and death. Most recently, large randomized trials among critically ill adults have examined whether balanced crystalloids result in less death or severe renal dysfunction than saline. Although some of these trials are still ongoing, a growing body of evidence raises fundamental concerns regarding saline as the primary intravenous crystalloid for critically ill adults and highlights fundamental unanswered questions for future research about fluid therapy in critical illness.
Project description:Patients with infective endocarditis (IE) have an elevated risk of renal dysfunction because of extensive systemic inflammation and use of nephrotoxic antibiotics. In this randomized, placebo-controlled trial, we investigated whether perioperative sodium bicarbonate administration could attenuate postoperative renal dysfunction in patients with IE undergoing cardiac surgery.Seventy patients randomly received sodium chloride (n?=?35) or sodium bicarbonate (n?=?35). Sodium bicarbonate was administered as a 0.5 mmol/kg loading dose for 1 h commencing with anesthetic induction, followed by a 0.15 mmol/kg/h infusion for 23 h. The primary outcome was peak serum creatinine (SCr) level during the first 48 h postoperatively. The incidence of acute kidney injury, SCr level, estimated glomerular filtration rate, and major morbidity endpoints were assessed postoperatively.The peak SCr during the first 48 h postoperatively (bicarbonate vs.1.01 (0.74, 1.37) mg/dl vs. 0.88 (0.76, 1.27) mg/dl, P?=?0.474) and the incidence of acute kidney injury (bicarbonate vs.29% vs. 23%, P?=?0.584) were similar in both groups. The postoperative increase in SCr above baseline was greater in the bicarbonate group than in the control group on postoperative day 2 (0.21 (0.07, 0.33) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P?=?0.028) and postoperative day 5 (0.23 (0.08, 0.36) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P?=?0.017).Perioperative sodium bicarbonate administration had no favorable impact on postoperative renal function and outcomes in patients with IE undergoing cardiac surgery. Instead, it was associated with possibly harmful renal effects, illustrated by a greater increase in SCr postoperatively, compared to control.ClinicalTrials.gov, NCT01920126 . Registered on 31 July 2013.
Project description:Background:Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation. Methods:A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl- ? 109 mmol/L) and required hyperosmolar treatment. Results:We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl- load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na+ concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, (p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups. Conclusions:Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl- load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results. Trial registration:clinicaltrials.gov # NCT03204955, registered on 6/28/2017.