lower-than-normal blood chloride levels
Betts, J. G., Young, K. A., Wise, J. A., Johnson, E., Poe, B., Kruse, D. H., … DeSaix, P. (n.d.). Anatomy and Physiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/anatomy-and-physiology
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Baseline and incident hypochloremia in chronic heart failure outpatients: Clinical correlates and prognostic role
Background: Electrolyte serum disorders are associated with poor outcome in chronic heart failure. The aim of this study sought to identify the main driver of incident hypochloremia in chronic HF (CHF) outpatients and to determine the prognostic value of baseline and incident hypochloremia.
Methods: Consecutive CHF outpatients were enrolled and clinical, laboratoristic and echocardiographic evaluations were performed at baseline and repeated yearly in a subgroup of patients. Baseline and incident hypochloremia were evaluated. During an up to 5-year follow-up, all-cause mortality was the primary end-point for outcome.
Results: Among 506 patients enrolled, 120 patients died during follow-up. At baseline, hypochloremia was present in 10% of patients and it was associated with mortality at univariate (HR: 3.25; 95%CI: 2.04-5.18; p<0.001) and at multivariate analysis (HR 2.14; 95%CI: 1.23-3.63; p: 0.005) after correction for well-established CHF prognostic markers. Among patients with repeated evaluations and without baseline hypochloremia, in 13% of these, incident hypochloremia occurred during follow-up and furosemide equivalent daily dose was its first determinant (HR for 1 mg/die: 1.008; 95%CI: 1.004-1.013; p<0.001) at forward stepwise logistic regression analysis. Finally, incident hypochloremia was associated with mortality at univariate (HR: 4.69; 95%CI: 2.69-8.19; p<0.001) as well as at multivariate analysis (HR: 2.97; 95%CI: 1.48-5.94; p: 0.002).
Conclusions: In CHF outpatients baseline and incident hypochloremia are independently associated with all-cause mortality, thus highlighting the prognostic role of serum chloride levels which are generally unconsidered. Future studies should evaluate if the strict monitoring and correction of hypochloremia could exert a beneficial effect on prognosis.
Hypochloraemia is associated with 28-day mortality in patients with septic shock: a retrospective analysis of a multicentre prospective registry
Objectives: Hyperchloraemia is associated with poor clinical outcomes in sepsis patients; however, this association is not well studied for hypochloraemia. We investigated the prevalence of chloride imbalance and the association between hypochloraemia and 28-day mortality in ED patients with septic shock.
Methods: A retrospective analysis of data from 11 multicentre EDs in the Republic of Korea prospectively collected from October 2015 to April 2018 was performed. Initial chloride levels were categorised as hypochloraemia, normochloraemia and hyperchloraemia, according to sodium chloride difference adjusted criteria. The primary outcome was 28-day mortality. A multivariate logistic regression model adjusting for age, sex, comorbidities, acid-base state, sepsis-related organ failure assessment (SOFA) score, lactate and albumin level was used to test the association between the three chloride categories and 28-day mortality.
Results: Among 2037 enrolled patients, 394 (19.3%), 1582 (77.7%) and 61 (3.0%) patients had hypochloraemia, normochloraemia and hyperchloraemia, respectively. The unadjusted 28-day mortality rate in patients with hypochloraemia was 27.4% (95% CI, 23.1% to 32.1%), which was higher than in patients with normochloraemia (19.7%; 95% CI, 17.8% to 21.8%). Hypochloraemia was associated with an increase in the risk of 28-day mortality (adjusted OR (aOR), 1.36, 95% CI, 1.00 to 1.83) after adjusting for confounders. However, hyperchloraemia was not associated with 28-day mortality (aOR 1.35, 95% CI, 0.82 to 2.24).
Conclusion: Hypochloraemia was more frequently observed than hyperchloraemia in ED patients with septic shock and it was associated with 28-day mortality.
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.