Abstract:Aims Despite recent advances in guideline-directed therapy, rehospitalization rates for acute decompensated heart failure (ADHF) remain high. Recently published studies demonstrated the emerging role of hypochloraemia as a predictor of poor outcomes in patients with ADHF. This study sought to determine the correlation between low serum chloride and 30 day hospital readmission in patients with ADHF.
Methods and resultsWe retrospectively reviewed electronic medical records of 1504 patients who were admitted to o… Show more
Background
This systematic review discusses a clinical physiology aspect of chloride in fluid therapy. Crystalloid solutions are one of the most widely used remedies. While generally used in medicine for almost 190 years, studies focused largely on their safety have only been published since the new millennium. The most widely used solution, normal saline, is most often referred to in this context. Its excessive administration results in hyperchloremic metabolic acidosis with other consequences, including higher mortality rates.
Methods
Original papers and review articles eligible for developing the present paper were identified by searching online in the electronic MEDLINE database. The keywords searched for included hyperchloremia, hypochloremia, and compound words containing the word “chloride,” infusion therapy, metabolic acidosis, renal failure, and review.
Results
A total of 21,758 papers published before 31 May 2020 were identified; of this number, 630 duplicates were removed from the list. Upon excluding articles based on their title or abstract, 1850 papers were screened, of which 63 full-text articles were assessed.
Conclusions
According to the latest medical concepts, dyschloremia (both hyperchloremia and hypochloremia) represents a factor indisputably having a negative effect on selected variables of clinical outcome. As infusion therapy can significantly impact chloride homeostasis of the body, the choice of infusion solutions should always take into account the potentially adverse impact of chloride content on chloremia and organ function.
Background
This systematic review discusses a clinical physiology aspect of chloride in fluid therapy. Crystalloid solutions are one of the most widely used remedies. While generally used in medicine for almost 190 years, studies focused largely on their safety have only been published since the new millennium. The most widely used solution, normal saline, is most often referred to in this context. Its excessive administration results in hyperchloremic metabolic acidosis with other consequences, including higher mortality rates.
Methods
Original papers and review articles eligible for developing the present paper were identified by searching online in the electronic MEDLINE database. The keywords searched for included hyperchloremia, hypochloremia, and compound words containing the word “chloride,” infusion therapy, metabolic acidosis, renal failure, and review.
Results
A total of 21,758 papers published before 31 May 2020 were identified; of this number, 630 duplicates were removed from the list. Upon excluding articles based on their title or abstract, 1850 papers were screened, of which 63 full-text articles were assessed.
Conclusions
According to the latest medical concepts, dyschloremia (both hyperchloremia and hypochloremia) represents a factor indisputably having a negative effect on selected variables of clinical outcome. As infusion therapy can significantly impact chloride homeostasis of the body, the choice of infusion solutions should always take into account the potentially adverse impact of chloride content on chloremia and organ function.
“…Further investigation on the association between hypochloremia and rehospitalization was done by Marchenko et al [28]. In their study, hypochloremia on either admission or discharge was found to be independently associated with a greater 30-day readmission rate.…”
Section: Clinical Trials -Chloride In Acute Hfmentioning
Clinical guidelines include diuretics for the treatment of heart failure (HF), not to decrease mortality but to decrease symptoms and hospitalizations. More attention has been paid to the worse outcomes, including mortality, associated with continual diuretic therapy due to hypochloremia. Studies have revealed a pivotal role for serum chloride in the pathophysiology of HF and is now a target of treatment to decrease mortality. The prognostic value of serum chloride in HF has been the subject of much attention. Mechanistically, the macula densa, a region in the renal juxtaglomerular apparatus, relies on chloride levels to sense salt and volume status. The recent discovery of with-no-lysine (K) (WNK) protein kinase as an intracellular chloride sensor sheds light on the possible reason of diuretic resistance in HF. The action of chloride on WNKs results in the upregulation of the sodium-potassium-chloride cotransporter and sodium-chloride cotransporter receptors, which could lead to increased electrolyte and fluid reabsorption. Genetic studies have revealed that a variant of a voltage-sensitive chloride channel (CLCNKA) gene leads to almost a 50% decrease in current amplitude and function of the renal chloride channel. This variant increases the risk of HF. Several trials exploring the prognostic value of chloride in both acute and chronic HF have shown mostly positive results, some even suggesting a stronger role than sodium. However, so far, interventional trials exploring serum chloride as a therapeutic target have been largely inconclusive. This study is a review of the pathophysiologic effects of hypochloremia in HF, the genetics of chloride channels, and clinical trials that are underway to investigate novel approaches to HF management.
“…Consistent with this idea, patients with hypochloraemia take higher doses of loop diuretics than those with normal chloride levels [ 3 – 12 ], but whether a high-dose diuretic is the cause of hypochloraemia or becomes necessary because of hypochloraemia-induced diuretic resistance is uncertain.…”
Section: Chloride and Outcomementioning
confidence: 99%
“…Hypochloraemia is a common electrolyte disturbance and marker of adverse outcome amongst patients with HF independent of other prognostic markers, including hyponatremia (Table 1 ) [ 3 – 12 ]. The mechanisms are poorly understood.…”
Hypochloraemia is a common electrolyte abnormality in patients with heart failure (HF). It has a strong association with adverse outcome regardless of HF phenotype and independent of other prognostic markers. How hypochloraemia develops in a patient with HF and how it might influence outcome are not clear, and in this review we explore the possible mechanisms. Patients with HF and hypochloraemia almost invariably take higher doses of loop diuretic than patients with normal chloride levels. However, renal chloride and bicarbonate homeostasis are closely linked, and the latter may be influenced by neurohormonal activation: it is likely that the etiology of hypochloraemia in patients with HF is multifactorial and due to more than just diuretic-induced urinary losses. There are multiple proposed mechanisms by which low chloride concentrations may lead to an adverse outcome in patients with HF: by increasing renin release; by a stimulatory effect on the with-no-lysine kinases which might increase renal sodium-chloride co-transporter activity; and by an adverse effect on myocardial conduction and contractility. None of these proposed mechanisms are proven in humans with HF. However, if true, it might suggest that hypochloraemia is a therapeutic target that might be amenable to treatment with acetazolamide or chloride supplementation.
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