Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among Critically Ill Adults With Sepsis*

Raghunathan, Karthik; Shaw, Andrew; Nathanson, Brian H.; Stürmer, Til; Brookhart, Alan; Stefan, Mihaela; Setoguchi, Soko; Beadles, Christopher; Lindenauer, Peter K.

doi:10.1097/ccm.0000000000000305

Cited by 345 publications

(256 citation statements)

References 30 publications

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“…The purpose of this was to demonstrate the association between chloride administration and outcome independent of administered fluid volume. In doing so, Shaw and colleagues were able to demonstrate, for the first time, an association between increasing amounts of chloride administered during crystalloid resuscitation and increased in-hospital mortality which persisted after controlling for the total volume of fluid administered [13], raising the possibility that the chloride content of resuscitation fluids might be a modifiable risk factor for adverse outcomes.This study adds to previous data which demonstrated an association between the use of chloride-rich fluids and adverse outcomes compared to the use of balanced solutions in surgical patients [9] and patients with sepsis [10] and is consistent with a single centre, open label, beforeand-after period pilot study which showed that a strategy Intensive Care Med …”

supporting

confidence: 88%

supporting

confidence: 88%

“…This study adds to previous data which demonstrated an association between the use of chloride-rich fluids and adverse outcomes compared to the use of balanced solutions in surgical patients [9] and patients with sepsis [10] and is consistent with a single centre, open label, beforeand-after period pilot study which showed that a strategy Intensive Care Med (2014) 40:1966-1968 DOI 10.1007/s00134-014-3531-1 EDITORIAL of avoiding chloride-rich fluid improved renal outcomes [8]. Overall, it appears that the association between the administration of chloride-rich fluids and adverse outcomes is robust, reproducible and most likely ''dose dependent''.…”

mentioning

confidence: 53%

“…Compared to low chloride solutions like Hartmann's, rapid infusion of 0.9 % saline results in acidosis due to reduced strong ion difference, reduced renal perfusion and glomerular filtration rate, a tendency towards reduced urinary output, and even a pronounced increase in body weight [5,6]. Recent data raise the possibility that administration of 0.9 % saline [7] may be harmful and suggest that using 'balanced' solutions with lower, more physiological, chloride concentrations than 0.9 % saline may be preferable [8][9][10].The relationship between the serum chloride concentration and outcome appears to be 'U-shaped' so that values outside of the normal physiological range are associated with an increased risk of death [11]. Positive fluid balance is also associated with an increased risk of death [12].…”

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confidence: 99%

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Crystalloid fluid therapy: is the balance tipping towards balanced solutions?

Young

Joannidis

2014

Intensive Care Med

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Intravenous saline solutions were first introduced into clinical practice in the Sunderland cholera epidemic of 1831 [1]. More than 150 years later, not only is 0.9 % saline the most commonly used intravenous fluid in critically ill patients, it is also the fluid that has been administered to the largest number of critically ill patients in randomised controlled trials [2,3]. It is cheap and readily available, and more than a million litres of intravenous 0.9 % saline are administered to patients around the world every day [1]; however, although it is widely known as 'normal saline', 0.9 % saline is neither normal nor physiological [4]. In fact, the concentration of chloride in 0.9 % saline is approximately 1.5 times that of normal plasma. Compared to low chloride solutions like Hartmann's, rapid infusion of 0.9 % saline results in acidosis due to reduced strong ion difference, reduced renal perfusion and glomerular filtration rate, a tendency towards reduced urinary output, and even a pronounced increase in body weight [5,6]. Recent data raise the possibility that administration of 0.9 % saline [7] may be harmful and suggest that using 'balanced' solutions with lower, more physiological, chloride concentrations than 0.9 % saline may be preferable [8][9][10].The relationship between the serum chloride concentration and outcome appears to be 'U-shaped' so that values outside of the normal physiological range are associated with an increased risk of death [11]. Positive fluid balance is also associated with an increased risk of death [12]. Because chloride loading and volume loading often occur together the relative contributions of chloride overload and volume overload to the apparent increased mortality risk are uncertain. In this issue of Intensive Care Medicine, Shaw and colleagues examine, among other things, the association between the 'volume-adjusted chloride load' and in-hospital mortality in more than 100,000 patients with tachycardia (heart rate over 90 bpm) and at least one other systemic inflammatory response syndrome (SIRS) criterion [13]. The purpose of this was to demonstrate the association between chloride administration and outcome independent of administered fluid volume. In doing so, Shaw and colleagues were able to demonstrate, for the first time, an association between increasing amounts of chloride administered during crystalloid resuscitation and increased in-hospital mortality which persisted after controlling for the total volume of fluid administered [13], raising the possibility that the chloride content of resuscitation fluids might be a modifiable risk factor for adverse outcomes.This study adds to previous data which demonstrated an association between the use of chloride-rich fluids and adverse outcomes compared to the use of balanced solutions in surgical patients [9] and patients with sepsis [10] and is consistent with a single centre, open label, beforeand-after period pilot study which showed that a strategy Intensive Care Med

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supporting

confidence: 88%

supporting

confidence: 88%

mentioning

confidence: 53%

mentioning

confidence: 99%

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Crystalloid fluid therapy: is the balance tipping towards balanced solutions?

Young

Joannidis

2014

Intensive Care Med

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“…It has been theorized that the formation of endomysial edema, and an associated increase in diffusion distance from blood vessel to muscle fibers, may contribute to muscle fiber damage in patients with septic shock (38). In observational and experimental models, hyperchloremia or chloride-rich fluids have been associated with fluid retention, reduced renal perfusion, AKI, and mortality (39)(40)(41)(42)(43)(44). If any of these effects on biological systems are clinically significant, it is plausible that one or a ORIGINAL RESEARCH combination of volume-related complications could result in a prolonged hospital stay, impaired mobility, and/or need for discharge to a healthcare facility.…”

Section: Comparison With Previous Studiesmentioning

confidence: 99%

Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

et al. 2015

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Rationale: Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown.Objectives: This study describes patterns of fluid management both during and after septic shock. We examined factors associated with volume overload upon intensive care unit (ICU) discharge. We then examined associations between volume overload upon ICU discharge, mobility limitation, and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. Methods:We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital between June 2009 and April 2012 who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subject's admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression.Measurements and Main Results: Eighty-six percent of patients had a positive fluid balance, and 35% had volume overload upon ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.33-5.27; P = 0.01) after adjusting for preexisting conditions and severity of illness. Only 42% of patients received at least one dose of a diuretic during their hospitalization. Volume overload upon ICU discharge was independently associated with inability to ambulate upon hospital discharge (OR, 2.29; 95% CI, 1.24-4.25; P = 0.01) and, in patients admitted from home, upon discharge to a healthcare facility (OR, 2.34; 95% CI, 1.1-4.98; P = 0.03).Conclusions: Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation.

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