Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children
S.C. Medicina e Chirurgia d’Accettazione e d’Urgenza, A.O. “Ordine Mauriziano”, Torino
What we already know about this topic
Fluid therapy is the most frequently adopted therapeutic intervention for resuscitation of patients presenting with shock in the Emergency Department, mainly because more than half of cases are due to sepsis or hypovolemia1. Even though cristalloids are the type of fluids used more often in this setting, only recently there has been an in-depth research activity in this field, whose main results are summarized in table 1 and 2
|Author, year||Studies included||Clinical setting||Sample size||Outcome||Results|
|Zhou*2||RCT||Critically ill patients||2262||28-days mortality||RR = 1,50 (C.I. 95% 0,40 – 5,65); p = 0,55.|
|Renal replacement therapy||RR = 0,96 (C.I. 95% 0,62 – 1,50); p = 0,87.|
|Hammond3||RCT and observational studies||Critically ill patients||30950||In-hospital or 28/30 days mortality||Only RCTs: RR = 0,94 (C.I. 95% 0,88 – 1,02)|
|Only observational studies: RR = 0,82 (C.I. 95% 0,75 – 0,90)|
|Renal replacement therapy||RR = 0,93 (C.I. 95% 0,74 – 1,17)|
|Liu4||RCT||Critically ill patients||20345||Mortality||RR = 0,93 (C.I. 95% 0,86 – 1,01); p = 0,08.|
|Renal replacement therapy||RR = 0,94 (C.I. 95% 0,69 – 1,27); p = 0,67.|
|Zayed5||RCT||Critically ill patients||19332||In-hospital mortality||OR = 0,92 (C.I. 95% 0,85 – 1,01); p = 0,09.|
|Renal replacement therapy||OR = 0,92 (C.I. 95% 0,67 – 1,28); p = 0,65|
Table 1. Overview of systematic reviews of studies comparing saline and balanced cristalloids. Studies including also postoperative patients or comparison with colloids have been excluded. RCT: randomized controlled trial; RR: relative risk; OR: odds ratio; C.I.: confidence interval. (*) Comparison between saline and balanced cristalloids.
|Author, year||Study design||Clinical setting||Sample size||Outcome||Results|
|Raghunanthan6||Observational retrospective (propensity-matched analysis)||ICU patients with sepsis||53448||In-hospital mortality||RR = 0,86 (C.I. 95% 0,78 – 0,94)|
|Renal replacement therapy||RR = 0,95 (C.I. 95% 0,76 – 1,19)|
|Young7||Multicentre RCT||ICU patients||2278||Mortality||RR = 0,88 (C.I. 95% 0,67 – 1,17); p = 0,4|
|Renal replacement therapy||RR = 0,96 (C.I. 95% 0,62 – 1,50); p = 0,91|
|Yunos8||Before-after restrospective observational||Emergency Department||10154||Mortality||OR = 1,13 (C.I. 95% 0,92 – 1,38) (P = 0.31).|
|Renal replacement therapy||OR = 0,60 (C.I. 95% 0,25 – 1,44)|
|Semler9||Multicentre RCT||ICU patients||15802||In-hospital mortality||OR = 0,90 (C.I. 95% 0,80 – 1,01); p = 0,06|
|Renal replacement therapy||OR = 0.84 (C.I. 95% 0,68 – 1,02); p = 0,08|
Table 2. Overview of relevant RCT or observational studies investigating the relative efficacy of saline and balanced cristalloids. Studies including also postoperative patients or comparison with colloids have been excluded. RCT: randomized controlled trial; RR: relative risk; OR: odds ratio; C.I.: confidence interval; ICU: Intensive Care Units
Overall, available evidence suggests that the choice of cristalloids solutions does not affect major outcome such mortality and renal replacement therapy for patients undergoing resuscitation. Recent guidelines and expert opinions incorporated these results: the NICE Guidance on intravenous fluid therapy in adults in hospital recommend to “use crystalloids that contain sodium in the range 130 – 154 mmol/l […]”10, a range of sodium concentrations that encompasses both saline and the majority of balanced solutions. On the same line we find other Authors, for whom “isotonic or balanced salt solutions are a pragmatic initial resuscitation fluid for the majority of acutely ill patients”, preferring normal saline for patients with hypovolemia and alkalosis11.
For patients with sepsis and septic shock, the 2016 Surviving Sepsis Campaign Guidelines “suggest using either balanced crystalloids or saline for fluid resuscitation of patients with sepsis or septic shock”, grading this statement as weak, supported by low quality evidence12.
The Cochrane review13
Title: Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children
Authors: Antequera Martín AM, Barea Mendoza JA, Muriel A, Sáez I, Chico-Fernández M, Estrada-Lorenzo JM, Plana MN.
Bibliographic citation: Cochrane Database Syst Rev 2019; 7: CD012247.
Objective: To assess the effects of buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children.
Included studies: randomized controlled trials.
Primary outcomes: Overall (in-hospital) mortality and acute kidney injury (AKI) during hospitalization as defined by RIFLE (risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease) criteria or by AKIN (Acute Kidney Injury Network) criteria
Secondary outcomes: discussed in “Comment and conclusion”.
Number of included studies: 21 studies.
Quality of included studies: overall quality of included studies was good; high risk of bias regarding randomization process or blinding was never observed in any of the included trials.
Number of patients: 20213
|Outcome||No. of studies / No. of patients||Odds Ratio (95% C.I.)||Quality of evidence|
|In-hospital mortality||14 / 19664||0,91 (0,83 – 1,01)||High|
|Mortality (only adults)||12 / 19539||0,91 (0,83 – 1,01)|
|Acute kidney injury||9 / 18701||0,92 (0,84 – 1,00)||Low|
Table 3. Results of the systematic review. Estimates below 1 favor buffered solution use. C.I.: confidence interval.
Comment and conclusions
Like other similar recently published documents, this systematic review has not been able to detect any statistically significant difference favoring the use of balanced cristalloids (Hartmann’s solution, Ringer’s lactate, Ringer’s acetate or Plasmalyte®) over normal saline for fluid resuscitation in critically ill patients.
From a clinical standpoint, the finding of a trend in favour of the use of buffered solutions should make them preferable to clinicians in patients without metabolic alkalosis or brain injury (where the relative ipotonicity of buffered solution roses some concern about detrimental effects on intracranial pressure). Indeed, even a small reduction of the risk of renal complications could be important in critically ill patients. For this reason, the reported an OR of 0,32 (C.I. 95% 0,05 – 2,14) for mortality in patients receiving Ringer lactate vs saline should be tested further in appropriately designed clinical trial for confirmation.
These clinical findings are grounded on pathophysiologic bases, again confirmed in the present meta-analysis where pH is lower and chloride concentration higher in subjects treated with normal saline; these alterations, in turn, have been correlated with worst survival and lower incidence of kidney injury14,15 .
The major limitation of this work is the heavy dependence from the large SMART study9 which population constitutes about 78% of the entire sample of the systematic review, indeed influencing the final results.
- Holler JG, et al. Etiology of shock in the Emergency Department: a 12-year population-based cohort study. Shock 2019; 51 (1): 60–67
- Zhou F-H, et al. Normal saline for intravenous fluid therapy in critically ill patients. Chin J Traumatol 2018; 21: 11e15.
- Hammond DA, et al. Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis. Ann Pharmacother. 2019 Jul 31:1060028019866420.
- Liu C, et al. Balanced crystalloids versus normal saline for fluid resuscitation in critically ill patients: A systematic review and meta-analysis with trial sequential analysis. Am J Emerg Med 2019; pii: S0735-6757(19)30149-4.
- Zayed YZM, et al. Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis. J Intensive Care 2018; 6: 51.
- Raghunathan K, et al. Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among Critically Ill Adults With Sepsis*. Crit Care Med 2014; 42:1585.
- Young P,et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit. The SPLIT Randomized Clinical Trial. JAMA 2015; 314 (16): 1701.
- Yunos NM, et al. Renal effects of an emergency department chloride restrictive intravenous fluid strategy in patients admitted to hospital for more than 48 hours. Emerg Med Australasia 2017; 29: 643.
- Semler MW, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med 2018; 378: 829.
- National Institute for clinical excellence (NICE). Intravenous fluid therapy in adults in hospital. Clinical guideline. Published: 10 December 2013. Accessed at: nice.org.uk/guidance/cg174.
- Myburgh JA, Mythen MG. Resuscitation Fluids. N Engl J Med 2013; 369: 1243-51.
- Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017 Mar;45(3):486-552.
- Antequera Martín AM, Barea Mendoza JA, Muriel A, Sáez I, Chico-Fernández M, Estrada-Lorenzo JM, Plana MN Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children. Cochrane Database Syst Rev2019; 7: CD012247
- Shaw AD, et al. Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Med 2014; 40:1897–1905.
- Yunos NM, et al. Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults. JAMA 2012; 308 (15): 1566-1572.