Usefulness of chloride levels for fluid resuscitation in patients undergoing targeted temperature management after out-of-hospital cardiac arrest

Abstract

Objective

Chloride is an important electrolyte in the body. In this study, we aimed to evaluate the associations between chloride levels on emergency department (ED) admission and neurologic outcomes by stratifying patients undergoing targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) into three groups (hyper/normo/hypochloremia); we also assessed the effect of changes in chloride levels from baseline over time on outcomes.

Methods

This retrospective, observational cohort study of 346 patients was conducted between 2011 and 2019. The chloride levels were categorized as hypochloremia, normochloremia, and hyperchloremia by predetermined definitions. The primary endpoint was poor neurologic outcomes after hospital discharge. We evaluated the associations between chloride levels on ED admission and neurologic outcomes and assess the effect of changes in chloride levels over time on clinical outcomes.

Results

On ED admission, compared with normochloremia, hypochloremia was significantly associated with unfavorable neurologic outcomes (OR, 2.668; 95% CI, 1.217–5.850, P = 0.014). Over time, unfavorable neurologic outcomes were significantly associated with increases in chloride levels in the hyperchloremia and normochloremia groups after ED admission. The rates of poor neurologic outcomes in the hyperchloremia and normochloremia groups were increased by 14.2% at Time-12, 20.1% at Time-24, and 9.3% at Time-48 with a 1-mEq/L increase in chloride levels.

Conclusion

In clinical practice, chloride levels can be routinely and serially measured cost-effectively. Thus, baseline chloride levels may be a promising tool for rapid risk stratification of patients after OHCA. For fluid resuscitation after cardiac arrest, a chloride-restricted solution may be an early therapeutic strategy.

Introduction

Out-of-hospital cardiac arrest (OHCA) is a common condition, and the incidence of EMS-assessed OHCA in adults is 140.7 per 100,000 populations. However, OHCA has high mortality and morbidity rates [1,2]. In OHCA, inadequate perfusion leads to multiple organ injuries and also results in metabolic and electrolyte disturbances [2]. Induced hypothermia or targeted temperature management (TTM) has recently been widely accepted as the gold standard of treatment for preventing secondary brain injury in OHCA patients [3]. To maximize TTM benefits, the clinical management of TTM focuses on minimizing the risks of several potential complications [3]. Because OHCA patients are cooled, induced hypothermia disturbs electrolyte levels and acid-base balances [3,4]. Intravenous fluid resuscitation is a mainstay of early treatment for post-cardiac arrest patients because most patients experience hemodynamical instability in post-return of spontaneous circulation (ROSC) after cardiac arrest and receive a rapid infusion of cold intravenous fluids to reach the target temperature in TTM [3,5].

Although intravenous crystalloid solutions have been commonly used in the intensive care of critically ill patients, whether crystalloid composition affects clinical outcomes remains unclear [6]. Chloride, a major electrolyte, is the most abundant anion in body fluid and affects acid-base balances [7,8]. Dyschloremia may be a sign of severity in critically ill patients [9]. Hypochloremia can be caused by several conditions in critically ill patients, including diuretic therapy, vomiting, gastric drainage, chronic respiratory acidosis, heart failure, and excess infusion of hypotonic solutions [9]. Hypochloremia is associated with increased mortality because of the development of metabolic alkalosis [7]. Moreover, hyperchloremia can be induced by osmotic diuresis, fever, excessive chloride administration during resuscitation with chloride-rich solutions, hypermetabolic states, and post-hypocapnia [9]. Hyperchloremic metabolic acidosis is associated with poor outcomes in critically ill patients [7]. Furthermore, disease severity is higher in patients with dyschloremia than in those with normochloremia [9]. In clinical practice, chloride levels are routinely and serially measured [8]. However, few studies have reported the importance of chloride in critically ill patients [8]. During the resuscitation of critically ill patients, 0.9% saline, a chloride-rich solution, has been widely used for treating patients in shock [7]. Similarly, fluid resuscitation is performed for patients receiving TTM after cardiac arrest [10]. However, whether a chloride-liberal or chloride-restricted solution affects favorable outcomes remains unknown [7,[11], [12], [13]]. Therefore, it is important to consider the condition of each critically ill patient when determining the intravenous fluid to be administered [14]. The guidelines for post-resuscitation also do not provide explicit standards for fluid selection for effective TTM in post-cardiac arrest patients [5]. Hypochloremia or hyperchloremia is independently associated with clinically poor outcomes in critically ill patients because of the incidence of metabolic acidosis or alkalosis, respectively [7].

Considering this information, we designed this study to examine chloride levels at baseline and their changes over time during TTM in post-resuscitation care. To the best of our knowledge, no studies have focused on the initial selection of a chloride-liberal or chloride-restricted solution to resuscitate OHCA patients. We hypothesized that abnormal baseline levels or changes in serum chloride levels could be used to predict patient severity and could guide the management of chloride levels in patients during TTM after OHCA. Therefore, by stratifying post-resuscitated patients into three groups (hyperchloremia, normochloremia, and hypochloremia), we aimed to evaluate the associations between serum chloride levels on ED admission and neurologic outcomes and assess the effect of changes in chloride levels over time on clinical outcomes.