SMART trail 2018

1. Journal Club

2. Balanced Crystalloids versus Saline
in Critically Ill Adults
SMART Investigators
and the Pragmatic Critical Care Research Group
Isotonic Solutions and Major Adverse Renal Events Trial (SMART)

3. Background
IV fluid resuscitation in ICU is a common therapeutic intervention
Historically 0.9% normal saline has been the most used
Administration of physiological saline is associated with high Cl
metabolic acidosis, AKI, death *
Several observational studies, use of balanced crystalliods
associated with lower AKI, RRT, death
In recent large pilot studies, there was no difference in patient
outcome**
*Young P et al. JAMA 2015; 314: 1701-1710.
**Semler MW et al.Am J Respir Crit Care Med 2017; 195: 1362-1372

4. Clinical applicationComposition of the study fluids
Na K Ca Mg Cl Acetate Lactate Gluconate Osmolarity pH
0.9%
saline
154 154 308 5.5
Lactated
Ringer’s
130 4 2.7 109 28 273 6.5
Plasma-
Lyte A®
140 5 3 98 27 23 294 7.4

5. Price of study fluid
Fluid Price (PMK) , baht/bag
0.9% saline 40
Lactated Ringer’s 55
Plasma-Lyte A® 480

6. M E T H O D

7. Study design
Pragmatic, unblinded, cluster-randomized on per-month basis, multiple-
crossover trial
N=15,802 patients admitted to ICU
Balanced crystalloids (LR or Plasma-Lyte A, n=7,942)
Normal saline (0.9% NaCl , n=7,860)
Setting: Vanderbilt University Medical Center ICUs
Enrollment: 2015-2017
Follow-up: 30 days
Analysis: Intention-to-treat

8. Population
Inclusion Criteria
Admission to any ICU at Vanderbilt university medical center
Eligible again if discharged and later readmitted to ICU
Exclusion Criteria
Age < 18 years

9. Randomizations

10. Flow of participants through the trial

11. Definition of
Major Adverse Kidney Events within 30 days (MAKE30)
One or more criteria met in 30 days after ICU admission and
before discharge
In-hospital death
New RRT (any modality of RRT)
Persistent renal dysfunction
Final creatinine before hospital discharge ≥ 200%
of baseline value in a patient not known to have
received RRT prior to ICU admission.

12. Outcomes
Primary outcome :
proportion of patients who met any criteria of MAKE30
Secondary clinical outcomes
in-hospital death before ICU discharge or at 30 days
ICU-free days
ventilator-free days
vasopressor-free days
days alive and free of RRT during 28 days after enrollment
Secondary renal outcomes
new receipt of RRT , persistent renal dysfunction, AKI stage 2 or higher

13. Statistical Analysis
Initial plan : enroll 8000 pts in 60 unit-months to detect 12% relative between-
group difference of MAKE-30.
Total duration of trial was increased to 82 unit-months.
Continuous variables are reported as means and SD or as medians and
interquartile ranges
Categorical variables are reported as frequencies and proportions
The primary analysis compared the incidence of the primary outcome in the
balanced-crystalloids and saline groups with a generalized, linear, mixed-
effects model that included fixed effects and random effects

14. R E S U L T S

15. Baseline characteristics of study population

18. Balanced crystalloid
0.9% NaCl
Balanced crystalloid
0.9% NaCl
Volume of Intravenous Isotonic Crystalloid
Administered According to Group

19. Balanced crystalloid
0.9% NaCl
0.9% NaCl
Balanced crystalloid
Plasma chloride and bicarbonate concentration
according to group

20. Components of the MAKE30 composite outcome
11.1 %
2.9%
6.6 %
6.4 %
10.3 %
2.5 %

23. Subgroup analysis of rates for composite outcome
of death, new RRT or persistent renal dysfunction

24. Indications for new RRT

25. D I S C U S S I O N

26. Discussion
Studies in healthy volunteers suggest saline decrease
renal perfusion through chloride-mediated renal vaso-
constriction
In preclinical models, high chloride content of saline has
been reported to cause hyperchloremia,acidosis
inflammation,renal vasoconstriction,acute kidney injury,30
hypotension,and death.

27. In this study, use of balanced crystalloids rather than saline
resulted in an absolute difference of 1.1 % points in favor of
balanced crystalloids in 1o
outcome
Our results suggest that use of balanced crystalloids rather
than saline might prevent 1 patient among every 94 patients
admitted to an ICU from the need for new RRT , from persistent
renal dysfunction, or from death.
Moreover, the difference in outcomes appeared to be greater for
patients with sepsis and larger volumes of isotonic crystalloid.
Discussion

28. Limitations
Single academic center limits generalizability.
Unblinded
Clinician’s decision to initiate RRT may be treatment bias
No analysis of LRS and Plasma-Lyte A

29. Conclusion
In critically ill adults, IV balanced crystalloids rather
than saline had a favorable effect on composite
outcome of MAKE30.

30. SALTED and SMART